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Sample records for hydrochloride zoledronic acid

  1. Synthesis of imidazol-1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

    OpenAIRE

    Singh, Santosh Kumar; Manne, Narendra; Ray, Purna Chandra; Pal, Manojit

    2008-01-01

    A convenient and practical synthesis of imidazol-1-yl-acetic acid hydrochloride was achieved via N-alkylation of imidazole using tert-butyl chloroacetate followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized imidazol-1-yl-acetic acid hydrochloride was then utilized to prepare zoledronic acid.

  2. Synthesis of imidazol-1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

    Science.gov (United States)

    Manne, Narendra; Ray, Purna Chandra

    2008-01-01

    Summary A convenient and practical synthesis of imidazol-1-yl-acetic acid hydrochloride was achieved via N-alkylation of imidazole using tert-butyl chloroacetate followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized imidazol-1-yl-acetic acid hydrochloride was then utilized to prepare zoledronic acid. PMID:19104672

  3. [Effects of zoledronic acid on osteoporosis patients in Japan.

    Science.gov (United States)

    Tanaka, Sakae

    2017-01-01

    Zoledronic acid is a bisphosphonate with the most potent anti-bone resorbing activity. Several previous studies demonstrated that zoledronic acid once a year significantly reduced the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women. In a phase Ⅲ 2-year placebo-controlled, randomized, double-blind comparative study in Japan(ZONE study)demonstrated that once-yearly infusion of zoledronic acid 5 mg increased lumbar spine and proximal femoral BMD, and reduced the incidence of vertebral and non-vertebral fractures in Japanese patients with primary osteoporosis compared to placebo.

  4. Fracture risk and zoledronic acid therapy in men with osteoporosis

    DEFF Research Database (Denmark)

    Boonen, Steven; Reginster, Jean-Yves; Kaufman, Jean-Marc

    2012-01-01

    Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.......Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis....

  5. [Efficacy of zoledronic acid for osteoporosis:evidence from studies abroad.

    Science.gov (United States)

    Inoue, Daisuke

    2017-01-01

    Zoledronic acid is a nitrogen-containing bisphosphonate that has the strongest and the most persistent anti-resorptive activity. Once-yearly zoledronic acid has recently been approved for the treatment of osteoporosis in Japan. This overview summarizes abundant evidence of zoledronic acid, obtained from studies abroad, for its efficacy for postmenopausal, male and glucocorticoid-induced osteoporosis.

  6. Human stromal cells are required for an anti-breast cancer effect of zoledronic acid

    NARCIS (Netherlands)

    Nienhuis, Hilde H.; Arjaans, Marlous; Timmer-Bosscha, Hetty; de Vries, Elisabeth G. E.; Schroder, Carolina P.

    2015-01-01

    Previous studies suggested that bisphosphonate zoledronic acid exerts an antitumor effect by interacting with the microenvironment. In this study, we aimed to elucidate the mechanism behind the anti-breast cancer effect of zoledronic acid. Here we showed that zoledronic acid did not influence in

  7. Zoledronic acid and clinical fractures and mortality after hip fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S

    2007-01-01

    BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were...... assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS......: The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures...

  8. Zoledronic acid in the treatment of osteoporosis: indications for use

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    Nataliya Vladimirovna Toroptsova

    2011-06-01

    Full Text Available The mechanism of action of the third-generation bisphosphonate zoledronic acid (Aclasta is described; the data of randomized clinical trials of its efficacy and tolerability are given. It is concluded that zoledronic acid intravenously administered once a year may be the drug of choice for increasing patients' adherence to therapy, particularly in polypharmacy that is common in the elderly and in cognitive disorders. In addition, the drug may be given to postmenopausal women once every 2 years for the prevention of osteoporosis.

  9. Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia

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    Chiara Di Pede

    2016-01-01

    Full Text Available We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD with severe and chronic pain who was successfully treated with zoledronic acid (ZOL: a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

  10. Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

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    El Saghir Nagi S

    2005-12-01

    Full Text Available Abstract Background Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. Case presentation We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. Conclusion Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.

  11. Dosing of zoledronic acid with its anti-tumor effects in breast cancer

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    Xinmin Zhao

    2015-09-01

    Full Text Available Bisphosphonates have played an important role in the treatment of breast cancer, mainly in patients with bone metastasis, by reducing the risk of fracture, spinal cord compression, and hypercalcemia. Zoledronic acid, the most frequently used intravenous agent, has been traditionally administered on a monthly dosing schedule. Preclinical studies have demonstrated that zoledronic acid can inhibit angiogenesis, invasion, and adhesion of tumor cells. Several clinical studies of different timings and schedules of zoledronic acid therapy have demonstrated its anti-tumor effects, as well as its protective effect on bone health, in postmenopausal women during adjuvant breast cancer therapy. In general, early initiation of zoledronic acid, concomitantly with adjuvant therapy, has been found to be most beneficial. However, questions remain over the most effective schedule of treatment and relative potency of zoledronic acid. Therefore, we review the existing clinical studies to examine the influence of dosing of zoledronic acid therapy on clinical outcomes in patients with breast cancer.

  12. Spontaneous acetabular periprosthetic fracture in a patient continuously having zoledronic acid.

    Science.gov (United States)

    Tantavisut, Saran; Tanavalee, Aree; Thanakit, Voranuch; Ngarmukos, Srihatach; Wilairatana, Vajara; Wangroongsub, Yongsak

    2014-09-01

    Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. This case report illustrates an undesirable consequence from prolonged usage of zoledronic acid in bone metastasis prevention. Periprosthetic acetabular fracture in a patient treated with zoledronic acid for 7 years was reported. The clinical presentation, radiographic and pathological results were described. This is a rare complication after total hip arthroplasty which should not be ignored especially in patients who received long term bisphosphonate.

  13. Spontaneous Acetabular Periprosthetic Fracture in a Patient Continuously Having Zoledronic Acid

    Science.gov (United States)

    Tantavisut, Saran; Thanakit, Voranuch; Ngarmukos, Srihatach; Wilairatana, Vajara; Wangroongsub, Yongsak

    2014-01-01

    Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. This case report illustrates an undesirable consequence from prolonged usage of zoledronic acid in bone metastasis prevention. Periprosthetic acetabular fracture in a patient treated with zoledronic acid for 7 years was reported. The clinical presentation, radiographic and pathological results were described. This is a rare complication after total hip arthroplasty which should not be ignored especially in patients who received long term bisphosphonate. PMID:25177464

  14. Zoledronic acid and clinical fractures and mortality after hip fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S

    2007-01-01

    BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were...... assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS...... in the two groups. CONCLUSIONS: An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254 [ClinicalTrials.gov].)....

  15. Zoledronic acid infusion for prevention and treatment of osteoporosis

    OpenAIRE

    Sunyecz, John A

    2010-01-01

    John A SunyeczLaurel Highlands Ob/Gyn, Hopwood, Pennsylvania, USA and MenopauseRx, Inc., Uniontown, PA, USAAbstract: Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) i...

  16. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    Science.gov (United States)

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  17. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S

    2011-01-01

    Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinical...

  18. Life-threatening hyperkalemia following zoledronic acid infusion for Paget's disease: a case report

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    Naysmith Morag

    2011-08-01

    Full Text Available Abstract Introduction Zoledronic acid is a highly effective treatment in Paget's disease for persistent bone pain and prevention of further progression of the disease. The commonest electrolyte abnormality is hypocalcemia. To the best of our knowledge this is the first case of hyperkalemia secondary to zoledronic acid to be published in the world literature. The commonest arrhythmia related to zoledronic acid is atrial fibrillation. Case presentation We describe the case of an 80-year-old Caucasian man, with a history of ischemic heart disease, who had an in-hospital cardiac arrest related to hyperkalemia. Increasing potassium levels were noted following his first zoledronic acid infusion for symptomatic control of bone pain secondary to Paget's disease. Our patient suffered a cardiac arrest 10 days following the zoledronic acid infusion. Our patient's biochemistry and electrocardiogram output were monitored until his death 26 days after his cardiac arrest. Our patient developed paroxysmal atrial fibrillation in the post-resuscitation period and there was persistent hyperkalemia that required prolonged treatment with calcium resonium. All other possible causes of hyperkalemia were excluded. Conclusion In our patient's case persistent hyperkalemia and life-threatening arrhythmias were associated with use of zoledronic acid. These side effects have not been reported before and the causative mechanism is far from clear as there are no obvious systemic effects of zoledronic acid. The combination of zoledronic acid with predisposing factors such as structural heart disease might account for the clinical picture we witnessed. As a result, electrolyte monitoring should be adopted early in zoledronic acid use. Further studies are required to elucidate the underlying mechanism of hyperkalemia and identify the target group of patients where zoledronic acid can be safely administered. Great caution is advised in patients with underlying heart conditions.

  19. Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

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    Yan W

    2013-01-01

    Full Text Available Li Chen,1 Yunfei Ding,2 Yongzhong Wang,3 Xingrong Liu,2 RJ Babu,1 WR Ravis,1 Weili Yan21Department of Pharmaceutical Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA; 2Department of Pharmaceutical Sciences, College of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, China; 3School of Life Sciences, Anhui University, Hefei, ChinaBackground: Zoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acid-polycytidylic acid [poly (I:C] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly.Methods: Cationic lipid-coated calcium phosphate nanoparticles (LCP were developed to enable intracellular codelivery of zoledronic acid and poly (I:C. LCP codelivering zoledronic acid and poly (I:C were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice.Results: LCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17 and high zoledronic acid encapsulation efficiency (94% were achieved. LCP loaded with zoledronic acid and poly (I:C had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P < 0.05. Furthermore, codelivery of zoledronic acid and poly (I:C by LCP had higher cytotoxicity than delivering poly (I:C alone by LCP (P < 0.05, indicating a synergism

  20. Zoledronic acid infusion for prevention and treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    John A Sunyecz

    2010-10-01

    Full Text Available John A SunyeczLaurel Highlands Ob/Gyn, Hopwood, Pennsylvania, USA and MenopauseRx, Inc., Uniontown, PA, USAAbstract: Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.Keywords: fractures, intravenous bisphosphonate, osteoporosis, zoledronic acid

  1. [Separation of zoledronic acid and its related substances by ion-pair reversed-phase high performance liquid chromatography].

    Science.gov (United States)

    Zhang, Xiaoqing; Jiang, Ye; Xu, Zhiru

    2004-07-01

    A rapid and simple ion-pair reversed-phase high performance liquid chromatographic method (HPLC) has been established for the routine analysis of zoledronic acid and its related substances. The chromatographic conditions were optimized based on the satisfactory separation of zoledronic acid from imidazol-1-ylacetic acid, their retention times and peak shape. The excellent separation of zoledronic acid from its related substances, including the remaining imidazol-1-ylacetic acid used in the synthesis of zoledronic acid and other impurities of oxidation and decomposition, was achieved within 9 min on a Hypersil C8 column with UV detection at 220 nm. The mobile phase was a mixture of methanol (20%) and 5 mmo/L phosphate buffer (80%) that contains 6 mmol/L tetrabutylammonium bromide. The resolution factor of zoledronic acid from its adjacent peak was more than 2.5. This is a simple and rapid method for the routine assay of zoledronic acid.

  2. Zoledronic acid in the management of metastatic bone disease.

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    Santini, Daniele; Fratto, Maria Elisabetta; Vincenzi, Bruno; Galluzzo, Sara; Tonini, Giuseppe

    2006-12-01

    Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. Moreover, in vivo preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. This comprehensive review critically reports the several preclinical evidences of action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In addition, all the clinical trials evaluating the effects of principal bisphosphonates on skeletal disease progression in patients with breast cancer, prostate cancer, non-small cell lung cancer and other cancers have been reported. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is actually approved for the treatment of bone metastases from any solid tumour in many countries. Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. This issue and the other topics relating to the safety of bisphosphonates are discussed in this review.

  3. [Sunitinib and zoledronic acid induced osteonecrosis of the jaw].

    Science.gov (United States)

    Soós, Balázs; Vajta, László; Szalma, József

    2015-11-15

    The tendency for bisphosphonate and non-bisphosphonate (eg.: antiresorptive or anti-angiogenesis drugs) induced osteonecrosis is increasing. Treatment of these patients is a challenge both for dentists and for oral and maxillofacial surgeons. Cooperation with the drug prescribing general medicine colleagues to prevent osteonecrosis is extremely important. Furthermore, prevention should include dental focus elimination, oral hygienic instructions and education, dental follow-up and, in case of manifest necrosis, referral to maxillofacial departments. Authors outline the difficulties of conservative and surgical treatment of a patient with sunitinib and zoledronic acid induced osteonecrosis. The patient became symptomless and the operated area healed entirely six and twelve months postoperatively. A long term success further follow-up is necessary to verify long-term success.

  4. Assessment of the Impact of Zoledronic Acid on Ovariectomized Osteoporosis Model Using Micro-CT Scanning.

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    Bo Shuai

    Full Text Available Prompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.96 8-week-old specific-pathogen-free C57BL/6 mice were randomly divided into 4 groups (24 per group: a sham group, an ovariectomized osteoporosis model group, an estradiol-treated group, and a zoledronic acid-treated group. Five months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT to acquire three-dimensional imagery of their cancellous bone microstructure. The impact of ovariectomy, the effect of estradiol, and the effect of zoledronic acid intervention on cancellous bone microstructure, as well as on the expression of β-catenin, were evaluated.The estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV, and β-catenin expression, when compared with those of the control group (P <0.01. In contrast, the structure model index, trabecular separation, and BS/BV were significantly lower compared with those of the model group (P <0.01. No differences were observed in the above parameters between animals of the zoledronic acid-treated and the estradiol-treated group.These results suggest that increased β-catenin expression may be the mechanism underlying zoledronic acid-related improvement in the cancellous bone microstructure in ovariectomized mice. Our findings provide a scientific rationale for using zoledronic acid as a therapeutic intervention to prevent bone loss in post-menopausal women.

  5. Zoledronic acid for prevention and treatment of osteoporosis.

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    Recknor, Chris

    2011-04-01

    Osteoporosis (OP) is associated with a high risk of fracture and disability and with substantial medical costs. This paper is a review of the intravenous (i.v.) bisphosphonate zoledronic acid 5 mg (ZOL), used in the treatment and prevention of OP. This is a review of the scientific literature, between 2003 and 2010, on the use of ZOL in patients with low bone mass or OP. ZOL, given as a single infusion once yearly, has proven efficacy in reducing risk of vertebral and hip fractures in postmenopausal women with OP. In men and women with a recent hip fracture, ZOL has been shown to reduce the incidence of future clinical fractures. Data also demonstrate an increase in bone mineral density in postmenopausal women with osteopenia, in men with OP, and in patients at risk for glucocorticoid-induced osteoporosis. The ZOL clinical program has shown this agent to be safe and generally well tolerated. Acute flu-like symptoms may occur following the first infusion of ZOL, but these are generally mild and transient, and decrease in frequency with subsequent infusions. Patients must have adequate renal function (creatinine clearance ≥ 35 ml/min) and be adequately hydrated prior to infusion. With orally administered bisphosphonates, patient compliance and persistence with weekly or monthly dosing are frequently suboptimal. The ability to administer i.v. ZOL once yearly over 15 min for the treatment of OP provides the advantage of guaranteeing medication compliance for the duration of the dosing interval.

  6. Zoledronic acid infusion for prevention and treatment of osteoporosis.

    Science.gov (United States)

    Sunyecz, John A

    2010-10-14

    Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass) and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.

  7. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

    Science.gov (United States)

    Wang, I-Te; Chou, Shou-Chu; Lin, Ying-Chin

    2014-12-01

    Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

  8. Vitamin D reduces musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

    Science.gov (United States)

    Catalano, Antonino; Morabito, Nancy; Atteritano, Marco; Basile, Giorgio; Cucinotta, Domenico; Lasco, Antonino

    2012-04-01

    The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P osteoporosis.

  9. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women

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    Irene Lambrinoudaki

    2008-09-01

    Full Text Available Irene Lambrinoudaki, Sophia Vlachou, Fotini Galapi, Dimitra Papadimitriou, K Papadias2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, GreeceAbstract: Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw.Keywords: zoledronic acid, postmenopausal osteoporosis, bisphosphonate

  10. Zoledronic Acid May Reduce Intraoperative Bleeding in Spinal Tumors: A Prospective Cohort Study

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    Juan Wu

    2015-01-01

    Full Text Available Between June 2010 and June 2011, 176 patients were divided into 2 groups: a group with spinal metastasis of solid tumors (n=157 and a group with multiple myeloma (n=19. Both groups were further divided into 2 subgroups: a group receiving zoledronic acid before surgery and a control group. The zoledronic acid subgroup of the solid tumors group was group A (n=81, the control subgroup of the solid tumors group was group B (n=76, the zoledronic acid subgroup of the multiple myeloma group was group C (n=10, and the control subgroup of the multiple myeloma group was group D (n=9. The average intraoperative blood loss during spinal surgery was as follows: 1311±691 mL in group A and 1752±740 mL in group B (P=0.000 and 1994±810 mL in group C and 3134±795 mL in group D (P=0.000. Patients receiving zoledronic acid before surgery had significantly less intraoperative bleeding than those who did not receive it. Preoperative use of zoledronic acid can effectively reduce intraoperative bleeding during surgery for the treatment of spinal tumors.

  11. Zoledronic Acid may reduce intraoperative bleeding in spinal tumors: a prospective cohort study.

    Science.gov (United States)

    Wu, Juan; Zheng, Wei; Tan, Yan; Hu, Xiao-Yuan; Huang, Quan; Fan, Kai-Hua; Ma, Jie; Xiao, Wen-Jing; Ren, Jian-Dong; Hou, Jun; Xiao, Jian-Ru

    2015-01-01

    Between June 2010 and June 2011, 176 patients were divided into 2 groups: a group with spinal metastasis of solid tumors (n = 157) and a group with multiple myeloma (n = 19). Both groups were further divided into 2 subgroups: a group receiving zoledronic acid before surgery and a control group. The zoledronic acid subgroup of the solid tumors group was group A (n = 81), the control subgroup of the solid tumors group was group B (n = 76), the zoledronic acid subgroup of the multiple myeloma group was group C (n = 10), and the control subgroup of the multiple myeloma group was group D (n = 9). The average intraoperative blood loss during spinal surgery was as follows: 1311 ± 691 mL in group A and 1752 ± 740 mL in group B (P = 0.000) and 1994 ± 810 mL in group C and 3134 ± 795 mL in group D (P = 0.000). Patients receiving zoledronic acid before surgery had significantly less intraoperative bleeding than those who did not receive it. Preoperative use of zoledronic acid can effectively reduce intraoperative bleeding during surgery for the treatment of spinal tumors.

  12. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S

    2010-01-01

    Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically...... evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. INTRODUCTION: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given...... soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. METHODS: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n¿=¿1...

  13. Transient changes in thyroid functions tests after zoledronic acid infusion.

    Science.gov (United States)

    Karga, Helen; Giagourta, Irene; Papaioannou, Garyphallia; Katsichti, Paraskevi; Pardalakis, Argyris; Kassi, Georgia; Zagoreou, Apostolia; Triantaphyllopoulou, Maria; Zerva, Cherry

    2011-01-01

    Zoledronic acid (ZA) induces an acute phase response in association with elevation of serum cytokines, which possibly alter the 3 types of iodothyronine deiodinase activity. We therefore studied the possible alteration in thyroid function tests by ZA. We investigated the acute changes in serum thyroid hormones, TSH, cortisol, white blood cells, CRP, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), before (0) and 1, 2 and 3 days after iv infusion of 5 mg ZA in 24 asymptomatic postmenopausal women with osteoporosis (ZA group) in comparison with a placebo group. In the majority of patients the ZA infusion was associated with acute phase response and fever within 24h after infusion which became attenuated on day three. Concurrently with increase in serum cortisol, CRP, IL-6 and TNF-α, on day 1 and 2, total serum T3 (TT3), free T3 (fT3), total T4 (TT4) and fT4 decreased with a nadir on day 2 in association with an increase in the fT4/fT3 ratio and reverse T3 (rT3) levels. All thyroid function changes returned to the baseline levels on day 3, with cytokines still at higher levels, although lower than those on day 2. Serum TSH remained essentially unchanged throughout the study. The changes in thyroid hormones were at least in part explained by the increased TNF-α, but not by IL-6. ZA induces short term changes in thyroid hormones, characteristic of nonthyroidal illness syndrome (NTIS), in association with an increase in TNF-α and IL-6.

  14. FES-Rowing versus Zoledronic Acid to Improve BoneHealth in SCI

    Science.gov (United States)

    2016-12-01

    statin use increases bone density after SCI. We also excluded diabetics (n=1) as poor bone quality has been reported in this population. We excluded 1... knowledge , this is the first report demonstrat ing a positive effect of zoledronic acid on bone loss at the knee in chronic SCI. Combination

  15. Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice.

    Science.gov (United States)

    Sieber, Patricia; Lardelli, Patrizia; Kraenzlin, Claude A; Kraenzlin, Marius E; Meier, Christian

    2013-02-01

    Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis. In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire. The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p 3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing. Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.

  16. Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid

    OpenAIRE

    Cohen, Philip R.

    2015-01-01

    Background:  Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon.  The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE).  Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Purpose:  Zoledronic acid-associated baboon syndrome is ...

  17. Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S

    2007-01-01

    BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were...... assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical...... infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival. (ClinicalTrials.gov number, NCT00046254.)....

  18. Reactive oxygen species and autophagy associated apoptosis and limitation of clonogenic survival induced by zoledronic acid in salivary adenoid cystic carcinoma cell line SACC-83.

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Ge

    Full Text Available Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.

  19. Symptomatic Hypocalcemia Associated with Zoledronic Acid Treatment for Osteoporosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdulmohsen H. Al Elq

    2013-03-01

    Full Text Available Intravenous bisphosphonates are widely used in the management of solid tumors, metastatic bone disease, metabolic bone diseases and hypercalcemia of malignancies. Recently, yearly intravenous injections of zoledronic acid, one of the potent nitrogen-containing bisphosphonates, have also been approved for the prevention and treatment of osteoporosis. Although infrequently observed, asymptomatic hypocalcemia mainly due to intravenous bisphosphonates has been documented. Here we report a female patient who exhibited profound symptomatic hypocalcemia after receiving intravenous zoledronic acid as treatment of postmenopausal osteoporosis. The patient was not assessed for calcium status prior to the intravenous bisphosphonate therapy, and she was later found to have severe vitamin D deficiency. To our knowledge, this is the first patient with symptomatic hypocalcemia to be reported after zoledronic acid was approved for the management of osteoporosis. We highlight the importance of evaluating calcium and vitamin D levels before initiating intravenous bisphosphonate treatment, particularly in the presence of widespread vitamin D deficiency and the likelihood of future increases in the prescription of intravenous bisphosphonates.

  20. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride....

  1. Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Jun Zhang; Ran Wang; Yi-Lei Zhao; Xiao-Hui Sun; Hong-Xing Zhao; Tan Lu; De-Cai Chen; Hai-Bin Xu

    2012-01-01

    Objective:To compare the effect of zoledronic acid in treatment and prevention of osteoporosis with placebo.Methods:Random control trials regarding zoledronic acid in treatment of osteoporosis were retrieved by selectingMedline,EMbase andPubmed databases tillApril2012. TheRevMan software was used for all of the statistical analysis.Results:A total of9 trials were included in this meta-analysis.The pooled effect showed that zoledronic acid could increase the bone mineral density by2.98 times compared with placebo, and reduce the rate of fracture in patients by32%.The results should the zoledronic acid intervention had significantly less serious adverse events than controls, and the odds ratio was0.81(0.76-0.87).The longer term intervention, more than12 months intervention, could gain a better prevention effect for osteoporosis(OR,95%CI forBMD was3.35,2.77-3.92; for fracture was0.67,0.54-0.82).Conclusions:This present study shows that zoledronic acid could be effective approach in the prevention of osteoporosis, and could increase the bone mineral density and reduce the risk of facture.

  2. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G.E.H.; Rijk, Peter P. van [University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Dahmane, Amel; Stevens, Wil H.M. [CIS bio International, Saclay (France); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Zonnenberg, Bernard A. [UMC Utrecht, Department of Internal Medicine, Utrecht (Netherlands)

    2008-04-15

    {sup 153}Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet {sup registered}) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa {sup registered}) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg {sup 153}Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before {sup 153}Sm-EDTMP treatment. Urine was collected 48 h after injection of {sup 153}Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of {sup 153}Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 {+-} 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 {+-} 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with {sup 153}Sm-EDTMP. Zoledronic acid treatment does not influence {sup 153}Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe. (orig.)

  3. Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.

    Science.gov (United States)

    Melisi, Davide; Caputo, Rosa; Damiano, Vincenzo; Bianco, Roberto; Veneziani, Bianca Maria; Bianco, A Raffaele; De Placido, Sabino; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-12-01

    Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting.

  4. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid

    DEFF Research Database (Denmark)

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H

    2016-01-01

    , albeit with long-term consequences of the disease, such as osteoporosis, becoming of increasing significance. The medical treatment of osteoporosis in patients with CF or after organ transplantation is still being explored, and no clear guidelines regarding the best choice of bisphosphonate exist. We...... report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte...

  5. Sandwich Structure-like Meshes Fabricated via Electrospinning for Controllable Release of Zoledronic Acid

    Institute of Scientific and Technical Information of China (English)

    LU Jian; LIU Jian-guo; SONG Xiao-feng; CHEN Xue-si; WU Xiao-dong

    2011-01-01

    Novel sandwich structure-like nanofiber multilayered meshes were fabricated via electrospinning. The purpose of the present work was to control zoledronic acid release via the novel structure of sandwich structure-like meshes. The in vitro release experiments reveal that the drug release speed and initial burst release were controllable by adjusting the thicknesses of electrospun barrier mesh and drug-loaded mesh. Compared with those of other drug delivery systems, the main advantages of the sandwich structure-like fiber meshes are facile preparation conditions and the generality for hydrophobic and hydrophilic pharmaceuticals.

  6. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    NARCIS (Netherlands)

    Lam, M.G.E.H.; Dahmane, Amel; Stevens, W.H.M.; Rijk, Peter P. van; Klerk, J.M.H. de; Zonnenberg, Bernard A.

    2008-01-01

    Purpose: 153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatmen

  7. Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats

    Directory of Open Access Journals (Sweden)

    Evandro Pereira Palacio

    2012-01-01

    Full Text Available Aim. To investigate the biomechanical effects of zoledronic acid (ZA on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O (n=40 and sham surgery (S (n=40. At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW was intraperitoneally administered: OZA (n=20, ODW (n=20, SZA (n=20, and SDW (n=20. The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N, yield point (N, and stiffness coefficient (N/mm of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy.

  8. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws

    OpenAIRE

    Sarkarat; Kalantar Motamedi; Jahanbani; Sepehri; Kahali; Nematollahi

    2014-01-01

    Background Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. Objectives The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Materials and Methods Seven rats were g...

  9. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture

    DEFF Research Database (Denmark)

    Eriksen, Erik Fink; Lyles, Kenneth W; Colón-Emeric, Cathleen S

    2009-01-01

    Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently unde...

  10. Bones, breasts, and bisphosphonates: rationale for the use of zoledronic acid in advanced and early breast cancer

    Directory of Open Access Journals (Sweden)

    Allan Lipton

    2011-03-01

    Full Text Available Allan LiptonMilton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA, USAAbstract: Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role.Keywords: anticancer, adjuvant therapy, bone metastasis, skeletal, zoledronic acid

  11. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.

    Science.gov (United States)

    Raje, N; Vadhan-Raj, S; Willenbacher, W; Terpos, E; Hungria, V; Spencer, A; Alexeeva, Y; Facon, T; Stewart, A K; Feng, A; Braun, A; Balakumaran, A; Roodman, G D

    2016-01-08

    In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.

  12. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  13. A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

    Directory of Open Access Journals (Sweden)

    Jiang Liu

    2013-01-01

    Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

  14. Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

    Science.gov (United States)

    Cimini, E; Piacentini, P; Sacchi, A; Gioia, C; Leone, S; Lauro, G M; Martini, F; Agrati, C

    2011-01-01

    Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

  15. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    OpenAIRE

    2008-01-01

    Purpose 153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Methods Patients with hormone-refractory prostate cancer ...

  16. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  17. Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined.

    Science.gov (United States)

    Lam, Marnix G E H; de Klerk, John M H; Zonnenberg, Bernard A

    2009-07-01

    Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.

  18. Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

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    Otaify, G A; Aglan, M S; Ibrahim, M M; Elnashar, M; El Banna, R A S; Temtamy, S A

    2016-01-01

    Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of

  19. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

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    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  20. Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

    Directory of Open Access Journals (Sweden)

    Sun SL

    2016-10-01

    Full Text Available Shengliang Sun,* Fuchao Wang,* Honglei Dou, Longqiang Zhang, Jiwen Li Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong, People’s Republic of China *These authors contributed equally to this work Background: This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.Methods: One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60 received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional + radiotherapy (optional + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60 were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS bone mineral density (BMD from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH and femoral neck (FN BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX and bone-specific alkaline phosphatase (BSAP concentrations.Results: Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast

  1. Oncologic doses of zoledronic acid induce site specific suppression of bone modelling in rice rats.

    Science.gov (United States)

    Exposto, C R; Oz, U; Callard, J S; Allen, M J; Khurana, H; Atri, A D'; Mo, X; Fernandez, S A; Tatakis, D N; Edmonds, K; Westgate, P M; Huja, S S

    2017-06-01

    To examine the effect of zoledronic acid (ZOL) on cortical bone modelling and healing of extraction sockets in the jaw bones of a rodent model. We hypothesized ZOL suppresses both the bone formation in the modelling mode in the jaw bones and alters the extraction site healing. Rice rats were administered saline solution and two dose regimens of ZOL: 0.1 mg/kg, twice a week, for 4 weeks (n=17, saline=8 & ZOL=9) and a higher dose of 0.4 mg/kg, weekly, for 9 weeks (n=30, saline=15 & ZOL=15). Two pairs of fluorochrome bone labels were administered. Extraction of maxillary teeth was performed in maxilla. Mineral apposition rate, mineralizing surface and bone formation rate (BFR) were quantified on periodontal (PDL), alveolar and basal bone surfaces, and in the trabecular bone of proximal tibia. Bone volume (BV) was evaluated at extraction sockets. Multivariate Gaussian models were used to account for repeated measurements, and analyzes were conducted in SAS V9.3. ZOL suppressed bone modelling (BFR/BS) at the PDL surfaces in the mandible (Pmodelling mode in the jaws demonstrates the site specific effects of ZOL in rice rats. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Pregnancy and Lactation-Associated Osteoporosis: Bone Histomorphometric Analysis and Response to Treatment with Zoledronic Acid.

    Science.gov (United States)

    Grizzo, Felipe Merchan Ferraz; da Silva Martins, Janaina; Pinheiro, Marcelo M; Jorgetti, Vanda; Carvalho, Maria Dalva Barros; Pelloso, Sandra Marisa

    2015-10-01

    Pregnancy and lactation-associated osteoporosis (PAO) is a rare condition with little known pathophysiology. Most cases are diagnosed in the third trimester of pregnancy or in the first weeks postpartum, particularly in first pregnancies. Vertebral fractures are most commonly observed and characterised by prolonged severe pain, functional limitations and a loss of height. Measurements of bone mineral density and biochemical markers of bone remodelling are the clinical methods most commonly used for the management of these patients. However, a bone biopsy with histomorphometric analysis has been considered to be the gold-standard. Few studies have evaluated the histomorphometry in patients with this clinical condition and none of them performed the procedure at the beginning of the clinical assessment. In this study, we report a case of PAO in a 31-year-old postpartum patient who had undergone a twin pregnancy. We describe the clinical, laboratory tests and imaging features. Bone histomorphometry showed a high resorption rate and excellent evolution after 1 year of treatment with intravenous zoledronic acid. Our data suggest that osteoclastogenesis plays a central role in the pathophysiological processes of this disease.

  3. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    Science.gov (United States)

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  4. Subgroup variations in bone mineral density response to zoledronic acid after hip fracture.

    Science.gov (United States)

    Magaziner, Jay S; Orwig, Denise L; Lyles, Kenneth W; Nordsletten, Lars; Boonen, Steven; Adachi, Jonathan D; Recknor, Chris; Colón-Emeric, Cathleen S; Mesenbrink, Peter; Bucci-Rechtweg, Christina; Su, Guoqin; Johnson, Rasheeda; Pieper, Carl F

    2014-12-01

    Minimizing post-fracture bone loss is an important aspect of recovery from hip fracture, and determination of factors that affect bone mineral density (BMD) response to treatment after hip fracture may assist in the development of targeted therapeutic interventions. A post hoc analysis of the HORIZON Recurrent Fracture Trial was done to determine the effect of zoledronic acid (ZOL) on total hip (TH) and femoral neck (FN) BMD in subgroups with low-trauma hip fracture. A total of 2127 patients were randomized (1:1) to yearly infusions of ZOL 5 mg (n = 1065) or placebo (n = 1062) within 90 days of operation for low-trauma hip fracture. The 1486 patients with a baseline and at least one post-baseline BMD assessment at TH or FN (ZOL = 745, placebo = 741) were included in the analyses. Percentage change from baseline in TH and FN BMD was assessed at months 12 and 24 and compared across subgroups of hip fracture patients. Percentage change from baseline in TH and FN BMD at months 12 and 24 was greater (p 6 weeks post-surgery; and for TH and FN BMD in patients with a history of one or more prior fractures. All interactions were limited to the first 12 months after treatment with none observed for the 24-month comparisons. (Clinical trial registration number NCT00046254.) © 2014 American Society for Bone and Mineral Research.

  5. Cost-Effectiveness of Zoledronic Acid to Prevent and Treat Postmenopausal Osteoporosis in Comparison with Routine Medical Treatment

    Science.gov (United States)

    Golmohamdi, Fateme Rostami; Abbasi, Mahnaz; Karyani, Ali Kazemi; Sari, Ali Akbari

    2016-01-01

    Introduction Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. Methods This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients. Outcomes were obtained from a systematic review. The Cost-Effectiveness Ratio (CER) and incremental cost-effectiveness ratio (ICER) for outcome of femoral neck Bone Mineral Density (BMD), hip trochanter BMD, total hip BMD and lumbar spine BMD and cost-benefit of consuming Zoledronic Acid were calculated for fracture outcome obtained from reviewing hospital records. Results The results and the ICER calculated for study outcomes indicated that one percent increase of BMD on femoral neck BMD requires further cost of $386. One percent increase of BMD on hip trochanter BMD requires further cost of $264. One percent increase of BMD on total hip BMD requires further cost of $388, one percent increase of BMD on lumbar spine BMD requires further cost of $347. The Cost Benefit Analysis (CBA) calculated for vertebral and hip fracture, non-vertebral fracture, any clinical fracture, and morphometric fracture for a 36-month period were about 0.82, 0.57, and 1.06, respectively. Vertebral and hip fractures, and non-vertebral fractures or any clinical fracture for a 12-month period were calculated as 1.14 and 0.64, respectively. In other words, Zoledronic acid consumption approach is a cheaper and better approach based on an economic assessment, and it can be considered as a dominant approach. Conclusion According to the cost-effectiveness of zoledronic acid in the prevention and treatment of osteoporosis in women, despite the costs, it is recommended that insurance coverage for the

  6. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state.

  7. Guided bone regeneration with local zoledronic acid and titanium barrier: An experimental study

    Science.gov (United States)

    Dundar, Serkan; Ozgur, Cem; Yaman, Ferhan; Cakmak, Omer; Saybak, Arif; Ozercan, Ibrahim Hanifi; Alan, Hilal; Artas, Gokhan; Nacakgedigi, Onur

    2016-01-01

    The aim of this study was to evaluate the effects on new bone formation of autogenous blood alone or in combination with zoledronic acid (ZA), a β-tricalcium phosphate (β-TCP) graft or ZA plus a β-TCP graft placed under titanium barriers. For this purpose, eight adult male New Zealand white rabbits were used in the study, each with four titanium barriers fixed around four sets of nine holes drilled in the calvarial bones. The study included four groups, each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous blood was placed under the titanium barriers. The three experimental groups were the AB+ZA group, with autogenous blood plus ZA, the AB+β-TCP group, with autogeneous blood plus a β-TCP graft, and the AB+β-TCP+ZA group, with autogeneous blood plus a β-TCP graft and ZA mixture under the titanium barriers. The animals were sacrificed after 3 months. The amounts of new bone formation identified histomorphometrically were found to be higher after 3 months than at the time of surgery in all groups. The differences between the groups were examined with histomorphometric analysis, and statistically significant differences were identified at the end of the 3 months. The bone formation rate in the AB+β-TCP+ZA group was determined to be significantly higher than that in the other groups (P<0.05). In the AB+ZA and AB+β-TCP groups, the bone formation rate was determined to be significantly higher than that in the AB group (P<0.05). No statistically significant difference in bone formation rate was observed between the AB+β-TCP and AB+ZA groups. Local ZA used with autogeneous blood and/or graft material appears to be a more effective method than the use of autogeneous blood or graft alone in bone augmentation executed with a titanium barrier. PMID:27698687

  8. Response of a co-culture model of epithelial cells and gingival fibroblasts to zoledronic acid

    Directory of Open Access Journals (Sweden)

    Fernanda Gonçalves BASSO

    Full Text Available Abstract Osteonecrosis of the jaw is an adverse effect of bisphosphonates. While the etiopathogenesis of this condition has been investigated, the interactions and effects of bisphosphonates on oral mucosa cells remain unclear. It is hypothesized that cell culture models, such as co-culture or three-dimensional cell culture models, can provide valuable insight. Therefore, the aim of this study was to evaluate the effects of zoledronic acid (ZA on epithelial cells and gingival fibroblasts in a co-culture model. Briefly, epithelial cells were seeded on transwell inserts and gingival fibroblasts were seeded in the lower well of 24-well plates. The latter were treated with ZA (5 μM for 24 or 48 h. Cell viability and synthesis of the inflammatory chemokine, CCL2, were subsequently assessed. Data were subjected to statistical analysis with a 5% significance level. In the presence of ZA, the epithelial cells exhibited significant toxicity in both cell culture models and at both time points. However, greater cytotoxicity was observed in the co-culture model. Greater viability for the gingival fibroblasts was also associated with the co-culture model, and ZA-mediated toxicity was observed for the 48 h time point. ZA promoted a significant increase in CCL2 synthesis in both sets of cells, with greater CCL2 synthesis detected in the gingival fibroblasts. However, this effect was diminished in the co-culture model. Taken together, these results confirm the specific response patterns of the cells seeded in the co-culture model and also demonstrate the protective mechanism that is mediated by epithelial/mesenchymal cell interactions upon exposure to ZA.

  9. Response of a co-culture model of epithelial cells and gingival fibroblasts to zoledronic acid.

    Science.gov (United States)

    Basso, Fernanda Gonçalves; Soares, Diana Gabriela; Pansani, Taisa Nogueira; Turrioni, Ana Paula Silveira; Scheffel, Débora Lopes; Hebling, Josimeri; Costa, Carlos Alberto de Souza

    2016-11-28

    Osteonecrosis of the jaw is an adverse effect of bisphosphonates. While the etiopathogenesis of this condition has been investigated, the interactions and effects of bisphosphonates on oral mucosa cells remain unclear. It is hypothesized that cell culture models, such as co-culture or three-dimensional cell culture models, can provide valuable insight. Therefore, the aim of this study was to evaluate the effects of zoledronic acid (ZA) on epithelial cells and gingival fibroblasts in a co-culture model. Briefly, epithelial cells were seeded on transwell inserts and gingival fibroblasts were seeded in the lower well of 24-well plates. The latter were treated with ZA (5 μM) for 24 or 48 h. Cell viability and synthesis of the inflammatory chemokine, CCL2, were subsequently assessed. Data were subjected to statistical analysis with a 5% significance level. In the presence of ZA, the epithelial cells exhibited significant toxicity in both cell culture models and at both time points. However, greater cytotoxicity was observed in the co-culture model. Greater viability for the gingival fibroblasts was also associated with the co-culture model, and ZA-mediated toxicity was observed for the 48 h time point. ZA promoted a significant increase in CCL2 synthesis in both sets of cells, with greater CCL2 synthesis detected in the gingival fibroblasts. However, this effect was diminished in the co-culture model. Taken together, these results confirm the specific response patterns of the cells seeded in the co-culture model and also demonstrate the protective mechanism that is mediated by epithelial/mesenchymal cell interactions upon exposure to ZA.

  10. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws.

    Science.gov (United States)

    Sarkarat, Farzin; Kalantar Motamedi, Mohammad Hosein; Jahanbani, Jahanfar; Sepehri, Dena; Kahali, Roozbeh; Nematollahi, Zahra

    2014-04-01

    Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Seven rats were given 0.04 mg Zoledronic acid intravenously once a week for five weeks. Two weeks later, the animals underwent extraction of their first lower molars, bilaterally. After clinical confirmation of the osteonecrosis, PRP was injected randomly into one of the extraction sockets of each rat. Three weeks later, all rats were sacrificed in order to obtain histological sections. The analysis of epithelialization was performed by McNamar's test, and the analysis of osteogenesis and angiogenesis was performed by the Wilcoxon Sign Rank test. P value was set at 0.05. We found no significant differences between the two groups regarding the amount of epithelialization, angiogenesis or sequestrum formation (P > 0.05), but a significant difference was seen between the two groups regarding the amount of existing vital bone (P < 0.05). Our study demonstrates positive results (preservation or regeneration of bone) using PRP in treatment of BRONJ. Although PRP may enhance osseous regeneration, long-term follow-ups are required to confirm its benefits.

  11. Comparison of effects of zoledronic acid and clodronate on the bone structure: imaginological and histomorphometrical study in vivo.

    Science.gov (United States)

    Martelli, Stephanie Joana Roman; Damian, Melissa Feres; Gomes, Ana Paula Neutzling; Schinestsck, André Ribeiro; Silva, Alexandre Emídio Ribeiro; Vasconcelos, Ana Carolina Uchoa

    2017-09-01

    To compare histologically and imaginologically the bone structure of rats' mandibles treated with bisphosphonates (BPs) and rats that did not receive BPs. Thirty-four rat specimens (Rattus novergicus, Wistar strain) were divided into three groups: (i) 12 rats treated with zoledronic acid; (ii) 12 rats treated with clodronate; and (iii) the control group, containing 10 rats that received saline solution. All individuals were exposed to cone beam computed tomography (CBCT). The images were processed and analyzed to obtain the Hounsfield scores, using the software OsiriX 7.0. Sixty-eight histological slides were obtained from the specimens and stained with hematoxylin and eosin (HE). Using the software Adobe Photoshop CS6, the histological areas containing non-vital bone were identified and quantified. Non-vital bone presented positive association with the zoledronic acid and clodronate groups. Statistically, no significant difference in bone density was observed among the groups. Based on the results, the BP therapy alone was sufficient to induce osteonecrosis. In addition, the CBCT was not a sensible method for detection of the early signs of bone modification in individuals under BP therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid

    Science.gov (United States)

    Li, Xing; Sun, Wen; Li, Jinbo; Wang, Mengmeng; Zhang, Hengwei; Pei, Lingpeng; Boyce, Brendan F.; Wang, Zhiyu; Xing, Lianping

    2017-01-01

    Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch−/− mice in vitro nor induce bone loss in Itch−/− mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP. PMID:28145497

  13. Endometrial Cancer Diagnosed by the Presence of Bone Metastasis and Treated with Zoledronic Acid: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Aiko Shigemitsu

    2010-12-01

    Full Text Available Bone metastasis from endometrial cancer is rare. We report a case of endometrial cancer which was diagnosed by the presence of bone metastasis and treated with zoledronic acid. A 57-year-old woman complaining of progressive right hip pain consulted an orthopedist. She had no gynecologic complaints. X-rays revealed an osteolytic lesion of the right ischium. Bone scintigraphy was subsequently carried out and showed isotope accumulation in the right ischium. Computed tomography revealed an enlarged uterus; the patient consequently consulted a gynecologist. Histological sections of an endometrial biopsy showed endometrioid adenocarcinoma. Hysterectomy and bilateral salpingo-oophorectomy, as well as bone biopsy of the right ischium, were therefore carried out. A moderately differentiated endometrioid adenocarcinoma was expressed in the corpus. Histopathological examination of the bone biopsy also revealed adenocarcinoma. The final diagnosis was stage IVB endometrial cancer with bone and lung metastasis. Good pain relief was achieved due to chemotherapy. However, 2 months after completion of the chemotherapy, the patient was administered zoledronic acid because her hip pain had gradually increased. Following zoledronic acid administration, the hip pain reduced. Radiotherapy was then given for the right ischial metastasis after the ninth course of zoledronic acid therapy because the metastasis site had increased and the possibility of a pathological fracture had risen. However, the patient died 21 months after the initial treatment because of disease progression.

  14. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  15. Treatment of osteoporotic intertrochanteric fractures by zoledronic acid injection combined with proximal femoral nail anti-rotation

    Institute of Scientific and Technical Information of China (English)

    Yong Li; Wen-Bo Zhao; De-Li Wang; Qing He; Qin Li; Fu-Xing Pei; Lei Liu

    2016-01-01

    Objective:To observe the clinical results of proximal femoral nail anti-rotation (PFNA) combined with zoledronic acid injection in the treatment of osteoporotic intertrochanteric fractures in the elderly.Methods:60 elderly patients with osteoporotic intertrochanteric fractures were diagnosed using a dual energy X-ray bone density instrument.Patients were randomly divided into treatment or control groups (30 cases in each group).Patients in both groups were treated by closed/open reduction and internal fixation using PFNA.In the treatment group,patients received one zoledronic phosphonic acid injection of 5 mg/100 ml via intravenous drip,in addition to 600 mg of Caltrate D (qd) and 0.25 μg of alpha ossification alcohol (qd).The control group received 600 mg of Caltrate D (qd) and 0.25 μg of alpha ossification alcohol (qd).The oral drugs were administered for 12 months.Bone pain relief was observed,and changes in the bone mineral density (BMD) of the lumbar and health-side hip were recorded.Clinical results were evaluated using the Visual Analogue Scale (VAS),Harris joint function score,and Osteoporosis Quality of Life Scale (OQOLS).Results:Compared with the control group,bone pain symptoms were significantly alleviated (p < 0.05) in the treatment group.In the treatment and control groups,both between-group and within-group differences in BMD were significantly increased in L1-4,femoral neck and trochanter (p < 0.05).No significant differences were found between the two groups in regard to the involved hip or the total rate of improvement at the end of the follow-up period,although cases in the treatment group had higher OQOLS scores than those of the controls (p =0.04).Cases in the treatment group healed more quickly than those in the control group [(13 ± 3.2) weeks vs (15 ± 4.6) weeks,p =0.02].During the follow-up period,cases in the treatment group had no new fractures,whereas 2 new cases of hip fracture and 2 cases of distal radial fractures were observed

  16. Efficacy and Safety of Single Dose Zoledronic Acid for Osteoporosis in Frail Seniors: A Randomized Clinical Trial

    Science.gov (United States)

    Greenspan, Susan L.; Perera, Subashan; Ferchak, Mary Anne; Nace, David A.; Resnick, Neil M.

    2016-01-01

    Importance 85% of institutionalized elderly have osteoporosis, with fracture rates 8–9 fold higher than observed among community-dwelling elderly. Yet most are untreated and excluded from pivotal osteoporosis trials. Objective Determine the efficacy and safety of zoledronic acid in frail elderly women. Design 2-year, randomized, placebo-controlled, double-blinded study conducted between December 2007 and March 2012. Setting Nursing home and assisted living facilities. Participants 181 women ≥ age 65 with osteoporosis including those with cognitive impairment, immobility, and multimorbidity. Intervention One 5 mg dose of zoledronic acid or placebo IV and daily calcium and vitamin D. Main Outcomes (1) Hip and spine bone mineral density (BMD) at 12 and 24 months and (2) adverse events. Results There were no baseline differences in age (mean=85.4±0.6 years), BMD, or functional or cognitive status, but the treatment group included more subjects with frailty, falls history, diabetes, and anticonvulsant use. BMD was available for 87% of participants at 12 months and 73% at 24 months. BMD changes were greater in the treatment group (p< 0.01): 3.2 ± 0.7 and 3.9 ± 0.7 percentage point differences (mean ± SE) in the total hip at 12 and 24 months respectively, and 1.8 ± 0.7 and 3.6 ± 0.7 at the spine (p<0.01); adjusted analyses were similar. The treatment and placebo groups’ fracture rates were 20% and 16%, respectively (OR=1.30; 95% CI=0.61–2.78); mortality rates were 16% and 13% (OR=1.24; 95% CI=0.54–2.86). Groups did not differ in the proportion of single fallers (28% vs. 24%; OR=1.24; 95% CI=0.64–2.42; p=0.52) but more subjects in the treatment group had multiple falls (49% vs. 35%; OR=1.83; 95% CI=1.01–3.33; p=0.047); this was no longer significant when adjusted for baseline frailty. Conclusions and Relevance In this group of frail, osteoporotic women, one dose of zoledronic acid improved BMD over 2 years. The clinical importance of nonsignificant

  17. Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay

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    Fehm Tanja

    2012-07-01

    Full Text Available Abstract Background The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA. Methods Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50, for IC90 and for the sensitivity index (IndexSUM. Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls. Results The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8% and TAC (12.9%, respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p  Conclusion Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.

  18. A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    R Bharath

    2013-01-01

    Full Text Available Aim: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA of foot in terms of clinical and radiological parameters. Material and Methods: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC. Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1oF. Results: Among the 40 patients, 30 (75% had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. Conclusion: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. 99m Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

  19. The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

    OpenAIRE

    ROMANI, ANTONELLO A.; Desenzani, Silvia; Morganti, Marina M.; Baroni, Maria Cristina; Borghetti, Angelo F.; Soliani, Paolo

    2010-01-01

    Abstract Purpose In TFK-1 and EGI-1 cholangiocarcinoma cell lines, zoledronic acid (ZOL) determines an S-phase block without apoptosis. Here, we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. Methods In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival protein?s pattern (BC...

  20. A ssessment of the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Lu; Zhe Zhang; Chao Yang; Jia-Cheng Zhang; Jun-Peng Ma; Peng Du; Jian Yang; Fu-Qiang Jiang; Xin-Li Jin; Peng Xie

    2016-01-01

    Objective:To study the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer.Methods: A total of 46 cases of patients with vertebral metastasis from lung cancer treated in our hospital between May 2012 and December 2015 were selected and divided into two groups, observation group (n=23) received transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment and control group only received transcatheter vertebral arterial chemoembolization therapy. Eight weeks after treatment, serum was collected to determine the levels of tumor markers, invasive molecules and bone transformation indicators.Results:8 weeks after treatment, serum CEA, NSE, Cyfra21-1, TK1, RCAS1, CatB, CatD, CatX, MMP7, MMP9, MMP13, N-MID, BALP, OC, PINP,β-CTX, NTX, ICTP and TRACP5b levels of observation group were significantly lower than those of control group.Conclusions:Transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment can more effectively kill the cancer cells in vertebral metastases, inhibit the secretion of protease and regulate bone metabolism balance.

  1. A novel {sup 99m}Tc-labeled dimethyl-substituted zoledronic acid (DMIDP) with improved bone imaging efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, L.; Lin, J.; Luo, S.; Wang, Y.; Cheng, W.; Zhang, S. [Jiangsu Institute of Nuclear Medicine, Wuxi (China). Key Laboratory of Nuclear Medicine

    2012-07-01

    A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2,4-dimethyl-1H-imidazol-1-yl)-ethane-1,1-diyldiphosphonic acid (DMIDP, dimezoledronate), was successfully prepared and labeled with {sup 99m}Tc in a high labeling yield. The biodistribution in mice shows that {sup 99m}Tc-DMIDP has significant advantage regarding bone resorption and clearance from soft tissues compared with {sup 99m}Tc-ZL and the clinically widely-used bone-imaging agent {sup 99m}Tc-MDP (methylenediphosphonic acid). Kinetics of blood clearance displayed that distribution half-life (T{sub 1/2{alpha}}) and elimination half-life (T{sub 1/2{beta}}) of {sup 99m}Tc-DMIDP were 2.53 min and 23.53 min, while those of {sup 99m}Tc-ZL were 2.28 and 52.63 min, respectively. Excellent images of the rabbit skeleton can be quickly obtained from {sup 99m}Tc-DMIDP, which was faster than {sup 99m}Tc-ZL and {sup 99m}Tc-MDP. The present findings indicate that {sup 99m}Tc-DMIDP possesses excellent potential for application as a novel bone scanning agent. (orig.)

  2. Development of superior bone scintigraphic agent from a series of {sup 99m}Tc-labeled zoledronic acid derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Qiu Ling, E-mail: qiulingwx@gmail.com [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Cheng Wen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.cn [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xue Li; Zhang Shu [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China)

    2012-05-15

    Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of {sup 99m}Tc-ZL and {sup 99m}Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent {sup 99m}Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that {sup 99m}Tc-IPeDP would be a novel superior bone scintigraphic agent. - Highlights: Black-Right-Pointing-Pointer Two novel diphosphonic acids were labeled with the {sup 99m}Tc in high labeling yield. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP had high uptake in skeletal system and rapid clearance from blood. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP reveals attractive biological features as superior bone scanning agent.

  3. Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice.

    Science.gov (United States)

    Wolfe, Tobie D; Pillai, Smitha Pankajavally Somanathan; Hildreth, Blake Eason; Lanigan, Lisa G; Martin, Chelsea K; Werbeck, Jillian L; Rosol, Thomas J

    2011-04-01

    Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct chemotherapy. Therapies that inhibit bone resorption, such as the bisphosphonates, may be an effective palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that therapy with a nitrogen-containing bisphosphonate, zoledronic acid (Zol), reduced OSA-induced bone lysis; however, Zol monotherapy or in combination with amputation was not effective at inhibiting pulmonary metastasis. While not reaching statistical significance, amputation of the tumor-bearing limb reduced the average incidence of lung metastases; however, this effect was nullified when Zol was added to the treatment protocol. In untreated mice, the magnitude of proximal tibial lysis was significantly correlated with the incidence of metastasis. The data support amputation alone for the management of appendicular OSA rather than combining amputation with Zol. However, in patients that are not viable candidates for amputation, Zol may be a useful palliative therapy for OSA by reducing the magnitude of lysis and therefore bone pain, despite the risk of increased pulmonary metastasis.

  4. Potentiated suppression of Dickkopf-1 in breast cancer by combined administration of the mevalonate pathway inhibitors zoledronic acid and statins.

    Science.gov (United States)

    Göbel, Andy; Browne, Andrew J; Thiele, Stefanie; Rauner, Martina; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-12-01

    The Wnt-inhibitor dickkopf-1 (DKK-1) promotes cancer-induced osteolytic bone lesions by direct inhibition of osteoblast differentiation and indirect activation of osteoclasts. DKK-1 is highly expressed in human breast cancer cells and can be suppressed by inhibitors of the mevalonate pathway such as statins and amino-bisphosphonates. However, supraphysiological concentrations are required to suppress DKK-1. We show that a sequential mevalonate pathway blockade using statins and amino-bisphosphonates suppresses DKK-1 more significantly than the individual agents alone. Thus, the reduction of the DKK-1 expression and secretion in the human osteotropic tumor cell lines MDA-MB-231, MDA-MET, and MDA-BONE by zoledronic acid was potentiated by the combination with low concentrations of statins (atorvastatin, simvastatin, and rosuvastatin) by up to 75% (p cancer-derived DKK-1-mediated inhibition of osteogenic markers in C2C12 cells (p pathway blockade allows for the combined use of low concentration of statins and amino-bisphosphonates. This combination still significantly suppresses breast cancer-derived DKK-1 to levels where it can no longer inhibit Wnt-mediated osteoblast differentiation.

  5. Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

    Science.gov (United States)

    Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

    2017-05-01

    Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

  6. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    Science.gov (United States)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  7. Bone Loss after Allogeneic Haematopoietic Stem Cell Transplantation: A Pilot Study on the Use of Zoledronic Acid

    Directory of Open Access Journals (Sweden)

    Andreas Hausmann

    2012-01-01

    Full Text Available Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT. The study aimed on tolerance and efficacy of zoledronic acid (ZA in patients after allo-HSCT. Methods. 40 patients’ with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs. BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip. Patients were evaluated for deoxypyridinoline (Dpd and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group. Among these patients, BMD increased from 0.97±0.15 to 1.10±0.18 g/cm² (LS baseline—2 yrs, Δ+11.6±6.0%, P<0.001 and from 0.82±0.10 to 0.91±0.10 g/cm² (FH baseline—2 yrs, Δ+7.5±7.0%, P<0.001. Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.

  8. Stability of ranitidine hydrochloride and amino acids in parenteral nutrient solutions.

    Science.gov (United States)

    Bullock, L; Parks, R B; Lampasona, V; Mullins, R E

    1985-12-01

    The stability of ranitidine hydrochloride in parenteral nutrient (PN) solutions and the effect of ranitidine hydrochloride on the amino acids in the PN solutions were studied. Six PN solutions (three each with amino acid contents of 2.125 and 4.25%) were prepared. Each PN solution also contained dextrose 25%, electrolytes, trace elements, vitamins, and heparin sodium. Ranitidine hydrochloride injection was added to four of the PN samples. Of the final samples, two contained no ranitidine, two contained ranitidine hydrochloride 50 micrograms/mL, and two contained ranitidine hydrochloride 100 micrograms/mL. Admixtures of ranitidine hydrochloride at the two concentrations in 0.9% sodium chloride injection were also prepared. Samples were observed for color change and tested for pH during storage at room temperature. Concentrations of amino acids were measured after 24 hours in samples without ranitidine and in samples containing ranitidine hydrochloride 100 micrograms/mL. Ranitidine hydrochloride content was determined by high-performance liquid chromatography at 12, 24, and 48 hours. No visual changes or pH changes occurred by 24 hours. All PN solutions became darker by 48 hours. The presence of ranitidine hydrochloride did not substantially affect amino acid concentrations. At 24 hours, at least 90% of the initial ranitidine concentrations remained in all samples. In three of the four PN samples at 48 hours, less than 90% of initial ranitidine concentrations remained. Ranitidine hydrochloride in concentrations of 50 and 100 micrograms/mL in parenteral nutrient solutions containing 4.25 and 2.125% crystalline amino acids is stable for 24 hours at room temperature. Under these conditions, concentrations of the amino acids contained in the PN solutions were not affected by the addition of ranitidine hydrochloride.

  9. Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors

    Science.gov (United States)

    Kopecka, Joanna; Porto, Stefania; Lusa, Sara; Gazzano, Elena; Salzano, Giuseppina; Pinzòn-Daza, Martha Leonor; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; De Rosa, Giuseppe; Caraglia, Michele; Riganti, Chiara

    2016-01-01

    The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking. The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization. NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors. Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells. PMID:26980746

  10. 14例唑来膦酸不良反应文献分析%Literature Analysis of 14 Cases of Adverse Drug Reactions Induced by Zoledronic Acid

    Institute of Scientific and Technical Information of China (English)

    韩一萱

    2014-01-01

    Objective:To analyze the general rules and characteristics of the adverse drug reactions(ADRs)induced by zoledronic acid so as to provide a reference for rational drug use in clinical practice.Methods:ADRs of zoledronic acid were retrieved from CNKI and VIP database since it was put into market in China and the data was analyzed statistically. Results:Totally 14 cases of ADRs(including 3 men and 11 women)caused by zoledronic acid were collected. The youngest patient was 43 years old and the oldest was 78 years old. The patients over the age of 50 showed the highest incidence(n= 11,78.6%). Their ADRs were involved in systemic damage such as musculo-skeletal system damage, metabolic and nutritional disorders, and hepatobiliary system damage,etc.Conclusion:Clinicians and pharmacists should understand the rules and characteristics of the ADRs induced by zoledronic acid and strengthen monitoring on drug use so as to reduce the incidence of ADR.%目的:分析唑来膦酸不良反应发生的规律及特点,为合理用药提供参考。方法:检索唑来膦酸在中国上市以来中国学术期刊全文数据库(CNKI)、维普中文科技期刊数据库(VIP)收载的不良反应文献进行统计分析。结果:唑来膦酸不良反应的个案报道共14例,男性3例,女性11例,年龄最小为43岁,最大为78岁,年龄50岁以上发生率较高(11例,78.6%);不良反应分别涉及全身性损害、肌肉骨骼系统损害、代谢和营养障碍、肝胆系统损害等。结论:临床医师和药师应了解唑来膦酸致不良反应的规律和特点,加强用药监测,以减少不良反应的发生。

  11. PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.

    Science.gov (United States)

    Bartlow, Christopher M; Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Butt, Bilal B; Damron, Timothy A

    2016-09-21

    Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  12. Zoledronic acid has differential anti-tumour activity in the pre-and post-menopausal bone microenvironment in vivo

    Science.gov (United States)

    Ottewell, Penelope D; Wang, Ning; Brown, Hannah K; Reeves, Kimberly J; Fowles, C Anne; Croucher, Peter I; Eaton, Colby L; Holen, Ingunn

    2014-01-01

    Purpose Clinical trials in early breast cancer have suggested that benefits of adjuvant bone targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and post-menopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumour cells. Here we report a differential anti-tumour effect of zoledronic acid (ZOL) in these two settings. Experimental design 12-week old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumour cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and post-menopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100ug/kg ZOL weekly. Tumour growth was assessed by in vivo imaging and effects on bone by RT-PCR, microCT, histomorphometry and measurements of bone markers. Disseminated tumour cells were detected by two-photon microscopy. Results OVX increased bone resorption and induced growth of disseminated tumour cells in bone. Tumours were detected in 83% of animals following OVX (post-menopausal model) compared to 17% following sham operation (pre-menopausal model). OVX had no effect on tumours outside of bone. OVX-induced tumour growth was completely prevented by ZOL, despite the presence of disseminated tumour cells. ZOL did not affect tumour growth in bone in the sham-operated animals. ZOL increased bone volume in both groups. Conclusions This is the first demonstration that tumour growth is driven by osteoclast-mediated mechanisms in models that mimic post-but not pre-menopausal bone, providing a biological rationale for the differential anti-tumour effects of ZOL reported in these settings. PMID:24687923

  13. Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents.

    Science.gov (United States)

    Koto, Kazutaka; Murata, Hiroaki; Kimura, Shinya; Horie, Naoyuki; Matsui, Takaaki; Nishigaki, Yasunori; Ryu, Kazuteru; Sakabe, Tomoya; Itoi, Megumi; Ashihara, Eishi; Maekawa, Taira; Fushiki, Shinji; Kubo, Toshikazu

    2010-07-01

    Third-generation bisphosphonates are known to inhibit bone resorption and also appear to exhibit direct anti-tumour activity. We previously reported that third-generation bisphosphonates such as zoledronic acid (ZOL) have a direct antitumour effect, and synergistically augment the effects of antitumor agents in osteosarcoma cells. There has been no report on the antitumor effect of ZOL against soft tissue sarcoma. The aim of this study was to evaluate the antitumor effect of this drug on a human fibrosarcoma cell line, in terms of proliferation and apoptosis, and, moreover, to evaluate the combined effects of ZOL with other antitumor drugs against the human fibrosarcoma cell line. HT1080 cells were treated with ZOL at various concentrations up to 10 microM, and then cell proliferation, cell cycle, nuclear morphology, and Western blot analyses were performed to study the antitumor effects of ZOL alone, and, moreover, HT1080 cells were treated with ZOL and other anticancer drugs such as paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, cisplatin, or methotrexate to investigate the combined effects using proliferation and cell cycle analyses. We found that ZOL strongly inhibited in vitro proliferation, arrested the cell cycle between S and G2/M phases, and induced the apoptosis of human fibrosarcoma cells. Moreover, ZOL augmented the effect of antitumor agents when administered concurrently with paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, and cisplatin in human fibrosarcoma cells. The treatment of fibrosarcoma with ordinary antitumor drugs is not fully effective. These findings suggest that ZOL directly affects the proliferation and survival of fibrosarcoma cells, and that the combined administration of ZOL with other antitumor agents may improve the efficacy of fibrosarcoma treatment. These results support the possibility that their combined use could be beneficial in the treatment of patients not only with

  14. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer.

    Science.gov (United States)

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients.

  15. Solvent effect on molecular structure, IR spectra, thermodynamic properties and chemical stability of zoledronic acid: DFT study.

    Science.gov (United States)

    Liu, Qingzhu; Qiu, Ling; Wang, Yang; Lv, Gaochao; Liu, Guiqing; Wang, Shanshan; Lin, Jianguo

    2016-04-01

    Zoledronic acid (ZL) has been used widely for treating skeletal diseases because of its high potency in inhibiting bone resorption. A detailed understanding of its physicochemical characteristics may be of great significance in both medicinal chemistry and structural biology for the design of novel bisphosphonates with higher activity. In the present work, the monoclinic (IM) and triclinic (IT) polymorphs of ZL in the gas phase and the aqueous phase were studied by density functional theory (DFT) method at the B3LYP/6-311++G** level. The polarizable continuum model (PCM) was employed to study the solvent effect on structures and properties. The optimized IM and IT conformations in both phases are in reasonable agreement with the experimental structures with the overall mean absolute percent deviation (MAPD%) less than 3.1 %. The presence of intramolecular hydrogen bond within both conformations was identified in the solvent. The IR spectra were simulated and assigned in detail, which agreed well with the experimental data. The intramolecular hydrogen bonding interactions resulted in the shift of vibrational frequencies of hydroxyl to the low band by 12-22 cm(-1) and 24-26 cm(-1) for IM and IT conformations, respectively. Their thermodynamic properties were also calculated based on the harmonic vibrational analysis, including standard heat capacity (C(°)p,m), entropy (S(°)m), and enthalpy (H(°)m). The molecular stability, hydrogen bonding interaction and other electronic properties have been further analyzed by the natural bond orbital (NBO), atoms in molecules (AIM), molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis.

  16. Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

    Science.gov (United States)

    Insalaco, Lavinia; Incorvaia, Lorena; Barraco, Nadia; Castiglia, Marta; Rizzo, Sergio; Santini, Daniele; Giordano, Antonio; Castorina, Sergio; Russo, Antonio

    2016-01-01

    Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent. PMID:27081088

  17. Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells.

    Science.gov (United States)

    Wang, Xiaolin; Wu, Guang; Cao, Guangxin; Yang, Lei; Xu, Haifei; Huang, Jian; Hou, Jianquan

    2015-09-01

    Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine‑5'-triphosphate (GTP)‑binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose‑6‑phosphate dehydrogenase (G6PD, the rate‑limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras‑GTP and phosphorylated‑extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.

  18. Novel therapeutic intervention for osteoporosis prepared with strontium hydroxyapatite and zoledronic acid: In vitro and pharmacodynamic evaluation.

    Science.gov (United States)

    Khajuria, Deepak Kumar; Vasireddi, Ramakrishna; Trebbin, Martin; Karasik, David; Razdan, Rema

    2017-02-01

    Osteoporosis therapeutics has been monopolized mainly by bisphosphonates, which are potent anti-osteoporotic drugs, while they do not promote bone formation or replenish the already resorbed bone. Although strontium substituted hydroxyapatite (SrHA) has been proclaimed to improve bone properties in an osteoporotic animal model, there is no published data on direct delivery of SrHA nanoparticles by bisphosphonate-like zoledronic acid (ZOL) to the bone. Therefore, this study was designed to investigate the potential of using SrHA/ZOL nanoparticle-based drug formulation in an ovariectomized rat model of postmenopausal osteoporosis. SrHA and SrHA/ZOL nanoparticles were prepared and characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Twelve weeks after ovariectomy, rats were treated with either single intravenous dose of SrHA/ZOL (100, 50 or 25μg/kg); ZOL (100μg/kg); or SrHA (100μg/kg). Saline-treated OVX and SHAM-OVX groups served as controls. The energy-dispersive X-ray (EDX) microanalysis of bone specimen obtained from SrHA/ZOL groups yielded range between 64.3±6.7 to 66.9±6.8 of calcium weight (wt) % and 1.64±0.6 to 1.74±0.8 of calcium/phosphorus (Ca/P) ratio which was significantly higher when compared with 39.7±9.3 calcium and 1.30±0.2 Ca/P ratio for OVX group. Moreover, the strontium wt% in SrHA/ZOL group (between 3.1±0.5 and 6.8±0.4) was significantly higher than SrHA group (1.8±0.9). These results confirmed targeted delivery of SrHA nanoparticles by ZOL to the bone. Therapy with SrHA/ZOL showed significant improvements in trabecular bone microarchitecture and mechanical strength as compared to ZOL or SrHA (posteoporosis.

  19. A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

    Directory of Open Access Journals (Sweden)

    Amelia O Clive

    Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

  20. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT).

    Science.gov (United States)

    Jacques, Richard M; Boonen, Steven; Cosman, Felicia; Reid, Ian R; Bauer, Douglas C; Black, Dennis M; Eastell, Richard

    2012-08-01

    Measurements of change in bone mineral density (BMD) are thought to be weak predictors of treatment effect on the reduction of fracture risk. In this study we report an alternative year-on-year approach for the estimation of treatment effect explained by BMD in which we examine the relationship between fracture risk and the most recent change in BMD. We studied 7736 postmenopausal women (ages 65 to 89 years) who were participants in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) and were randomized to either intravenous administration of zoledronic acid or placebo. The percentage of treatment effect explained by change in total hip BMD was estimated using the alternative year-on-year approach and the standard approach of looking at change over 3 years. We also studied a subset of 1132 women in whom procollagen type 1 amino-terminal propeptide (PINP) was measured at baseline and 12 months, to estimate the percentage of treatment effect explained by change in PINP. Regardless of the method used, the change in total hip BMD explained a large percentage of the effect of zoledronic acid in reducing new vertebral fracture risk (40%; 95% CI, 30% to 54%; for the 3-year analysis). The treatment effects for nonvertebral fracture were not statistically significant for the year-on-year analysis but 3-year change in BMD explained 61% (95% CI, 24% to 156%) of treatment effect. Change in PINP explained 58% (95% CI, 15% to 222%) of the effect of zoledronic acid in reducing new vertebral fracture risk. We conclude that our estimates of the percentage of treatment effect explained may be higher than in previous studies because of high compliance with zoledronic acid (due to its once-yearly intravenous administration). Previous studies may have underestimated the relationship between BMD change and the effect of treatment on fracture risk. Copyright © 2012 American Society for Bone and Mineral Research.

  1. A multicenter phase Ⅱ trial of domestic product of zoledronic acid in the treatment of malignant hypercalcemia%国产唑来膦酸治疗肿瘤高钙血症多中心Ⅱ期临床观察

    Institute of Scientific and Technical Information of China (English)

    Lijun Di; Jun Ren; Ying Yan

    2007-01-01

    Objective: To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia. Methods: A multi-center, open phase Ⅱ clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min. The level of blood calcium and side effects were recorded regularly within 28 days after injection. Results: One case was dropped out due to bad compliance. The complete response rate (the corrected serum calcium was reduced to normal level) was 100.00% (14/14). The medium time of complete response rate was 5.07 days. The medium maintain time was 22.30 days. Slight, or moderate fever was observed. Conclusion: Zoledronic acid can effectively reduce the malignant hypercalcemia. The use of zoledronic acid appears to be safety and convenient.

  2. SIMULTANEOUS ESTIMATION OF MEFENAMIC ACID AND DICYCLOMINE HYDROCHLORIDE BY SPECTROSCOPIC METHODS

    Directory of Open Access Journals (Sweden)

    D.N. Prajapati et al

    2012-10-01

    Full Text Available A novel, simple, accurate, sensitive, reproducible, economical spectroscopic method was developed and validated for the determination of Mefenamic acid and Dicyclomine hydrochloride in combined dosage form. Three different analytical methods, Absorption correction method, Differential derivative method, Simultaneous equation method were developed for estimation of Dicyclomine hydrochloride(10mg and Mefenamic acid (250mg in tablet dosage form. wavelength for estimation was 223nm for Dicyclomine hydrochloride and 308.60nm for Mefenamic acid in absorption correction method. 211.60nm was Zero crossing point of Mefenamic acid and 308.80nm was Zero crossing point of Dicyclomine hydrochloride which can estimate in differential derivative method. Simultaneous equation method was developed in NaOH which was linear in the range of 1-6µg/ml for Dicyclomine hydrochloride and 25-150µg/ml for Mefenamic acid, the correlation coefficient obtained was nearer to one. The method was validated for linearity, accuracy and precision as per ICH guidelines. The developed and validated method was successfully used for the quantitative analysis of commercially available dosage form.

  3. Mechanism of cisplatin combined with zoledronic acid on lung cancer A549 cells%顺铂联合唑来膦酸对肺癌A549细胞增殖的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    茆勇; 马凤锦; 黄朝晖; 许林; 游庆军; 华东

    2011-01-01

    Objective To investigate the function of cisplatin combined with Zoledronic acid on proliferation and mechanisms of A549 cells.Methods ( 1 ) Methyl thiazol tetrazolium (MTT) assay and Annexin V-FITC/PI double-staining flow cytometry were employed to observe the effects of cisplatin combined with Zoledronic acid upon anti-proliferation and apoptosis respectively.Reverse transcription-polymerase chain reaction (RT-PCR) was applied to assay mRNA expression of MDC1 among different groups.Results Inhibition of the cell proliferation was observed under the treatment of combined cisplatin and zoledronic acid (39.16 ±4.94)%,superior to the treatment of zoledronic acid ( 19.66 ±4.57)% or cisplatin ( 16.87 ± 2.50) %.Combined group induced A549 cells apoptosis ( 32.30 ± O.50 ) %,compared with cisplatin (23.90 ± 2.46) %,zoledronic acid ( 18.87 ± 3.04 ) %,the difference was statistically significant; cisplatin after zoledronic acid treatment of A549 cells M DC1 mRNA expression (0.134 ± 0.037 )was significantly decreased compared with single-drug,zoledronic acid ( 0.208 ± 0.040 ) and cisplatin (0.356 ± 0.033) ( P < 0.05 ).Conclusion Zoledronic acid or cisplatin can significantly inhibit A549 cell proliferation and markedly induce the apoptosis.Zoledronic acid and cisplatin in a synergistic way inhibited the cell proliferation and induced apoptosis on A549 cell.The downregulated expression level of MDC1 mRNA may involved in the mechanism of synergistic effect.%目的 观察顺铂联合唑来膦酸对肺癌A-549细胞增殖的影响并探讨其作用机制.方法 以噻唑蓝(MTT)比色法观察顺铂联合唑来膦酸对A549细胞增殖的影响,以Annexin-V/PI双染法检测细胞凋亡,逆转录-聚合酶链反应(RT-PCR)检测DNA损伤检查点蛋白调节因子1(MDC1)mRNA的表达.结果 顺铂联合唑来膦酸对A549细胞增殖的抑制率(39.16±4.94)%高于顺铂(16.87±2.50)%、唑来膦酸(19.66±4.57)%;联合用药诱导A549

  4. Zoledronic Acid Injection

    Science.gov (United States)

    ... called bisphosphonates. It works by slowing bone breakdown, increasing bone density (thickness), and decreasing the amount of ... parts of the body); anemia (condition in which red blood cells cannot bring enough oxygen to other parts of ...

  5. 唑来膦酸促进口腔种植体骨结合的研究现状%Zoledronic acid promotes osseointegration of dental implant

    Institute of Scientific and Technical Information of China (English)

    谢淑娟; 占柳

    2012-01-01

    种植体的骨整合是目前口腔学界种植义齿的研究热点.改善种植体的骨结合,增加种植体周围的骨量,可以较好的提高种植体的稳定性,从而提高种植体成功率和延长种植体使用寿命.双磷酸盐( bisphosphonate,BPs)类药物的新生力量——唑来膦酸( Zoledronic acid),以其在BPs类药物中具有最强效的抗骨质吸收能力吸引了众多关注,在临床成功应用后,口腔专家进一步研究其在种植体方面的良好效应,通过多项实验项目观察发现其具有改善种植体骨结合的效用,并且与其他药物联合应用时可以得到更好的效果,有望投入临床,应用前景不可小觑.%Osseointegration is now the focus of research on dental implant. It can improve the stability of the implant, and hence increase its success rate and prolong its life. Bisphosphonates-zoledronic acid, with its most powerful anti-bone resorption ability among bisphosphonates (BPs) , has attracted a lot of attention to the very success in its clinical application. Recently, dental experts have further studied its good effects in tooth implant by a number of pilot projects. Experiments show that it can improve osseointegration and produce better effect when combined with other drugs.

  6. Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

    Institute of Scientific and Technical Information of China (English)

    De-gang YU; Shen LIU; Zhen-an ZHU; Bo YU; Yuan-qing MAO; Xin ZHAO; Xiao-qing WANG; Hui-feng DING; Lei CAO; Guang-wang LIU; Shao-bo NIE

    2012-01-01

    Aim:To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model.Methods:Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats.Zoledronic acid (ZOL,100 μg/kg,sc,twice a week) was administered starting immediately,early (from 4 weeks) or late (from 8 weeks) after OA induction.The degeneration of articular cartilage was evaluated with toluidine blue O staining.Subchondral bone remodeling was evaluated with X-ray micro-CT scanning.Joint pain was measured with respect to weight-bearing asymmetry.Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis.The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold.Results:Progressive cartilage loss was observed during 12 weeks after OA induction.Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks),but as increased bone accretion at advanced stages (8 weeks).Immediately and early ZOL administration significantly improved subchondral microstructural parameters,attenuated cartilage degeneration,reduced weight-bearing asymmetry and CGRP expression,whereas the late ZOL administration had no significant effects.Conclusion:The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain.To obtain the maximum efficacy,bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

  7. Clinical trials progression of anti-cancer effects exerted by zoledronic acid%唑来膦酸抗肿瘤作用的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    王增; 卢红阳; 翁琳

    2011-01-01

    Zoledronic acid, the third generation of nitrogen-containing bisphosphonate, is a potent inhibitor of osteoclastic bone resorption by inhibiting osteoclast activity and inducing os-teoclast apoptosis and is currently approved for the treatment of tumor-induced hypercalcemia and the reduction and delay of skeletal complications in advanced bone-related malignancies. Data from preclinical studies of zoledronic acid suggest its definite anti-tumor effect. Recently, as several zoledronic acid related clinical trials are carried out, the anti-tumor effect of zoledronic acid attracts people's attention. These clinical trials show that zoledronic acid may improvetreatment response of multiple myeloma, breast cancer, prostate cancer and lung cancer including prolonging the disease free survival (DFS) and overall survival (OS). However, some important questions remain, including optimal dosing, initiation and duration of therapy, to be studied in further investigations. Here, we summarized the potential role of zoledronic acid in cancer treatment.%唑来膦酸是第三代双膦酸盐类药物,主要通过抑制破骨细胞的活性和诱导破骨细胞凋亡来抑制骨吸收,目前用于治疗恶性高钙血症、控制恶性肿瘤骨转移等.多个临床前研究显示唑来膦酸具有明确的抗肿瘤作用.近年来,随着多项临床试验的开展,唑来膦酸潜在的抗肿瘤作用也越来越受到关注.多个临床研究结果表明,唑来膦酸能改善多发性骨髓瘤,乳腺癌、前列腺癌、肺癌等恶性肿瘤治疗的疗效,包括延长患者的总生存时间和无病生存期等.然而,对于唑来膦酸与其他抗肿瘤治疗合用的最佳方案和剂量、持续时间还需要进一步的研究.在此,本文就唑表膦酸抗肿瘤作用的临床研究进展作一综述.

  8. Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

    Science.gov (United States)

    Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo

    2016-03-01

    Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (Plaser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of osteocalcin. Thus, laser irradiation could be considered a way to improve socket healing in conditions at risk for MRONJ development.

  9. Coupling of Carbon Dioxide with Epoxides Catalyzed by Amino Acid Hydrochloride Salts

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Using amino acid hydrochloride salt as a catalyst, the coupling reaction of CO2 with epoxides could proceed smoothly to give cyclic carbonates in very good yields and high selectivity. The reaction conditions such as the pressure of carbon dioxide, reaction temperature, time and catalyst loading were carefully investigated.

  10. Esterification of pseudoephedrine hydrochloride by citric acid in a solid dose pharmaceutical preparation.

    Science.gov (United States)

    Goel, Alok; Zhao, Zhicheng; Sørensen, Dan; Zhou, Jay; Zhang, Fa

    2016-09-10

    Esterification of pseudoephedrine hydrochloride (PSE) by citric acid was observed in a solid dose pharmaceutical preparation at room temperature and accelerated stability condition (40°C/75% relative humidity). The esterification of PSE with citric acid was confirmed by a solid-state binary reaction in the presence of minor level of water at elevated temperature to generate three isomeric esters. The structures of the pseudoephedrine citric acid esters were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Occurrence of esterification in solid state, instead of amidation which is generally more favorable than esterification, is likely due to remaining HCl salt form of solid pseudoephedrine hydrochloride to protect its amino group from amidation with citric acid. In contrast, the esterification was not observed from solution reaction between PSE and citric acid.

  11. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT).

    Science.gov (United States)

    Black, Dennis M; Reid, Ian R; Boonen, Steven; Bucci-Rechtweg, Christina; Cauley, Jane A; Cosman, Felicia; Cummings, Steven R; Hue, Trisha F; Lippuner, Kurt; Lakatos, Peter; Leung, Ping Chung; Man, Zulema; Martinez, Ruvie Lou Maria; Tan, Monique; Ruzycky, Mary Ellen; Su, Guoqin; Eastell, Richard

    2012-02-01

    Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy

  12. Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study.

    Directory of Open Access Journals (Sweden)

    Yoshie Hasegawa

    Full Text Available Zoledronic acid (ZOL is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT.Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95 or the CTZ group (n = 93 from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2, followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8% was doubled to CT group (7.7%, respectively (one-sided chi-square test, p = 0.068, though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071, and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112. Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and

  13. Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study).

    Science.gov (United States)

    Hasegawa, Yoshie; Tanino, Hirokazu; Horiguchi, Jun; Miura, Daishu; Ishikawa, Takashi; Hayashi, Mitsuhiro; Takao, Shintaro; Kim, Seung Jin; Yamagami, Kazuhiko; Miyashita, Masaru; Konishi, Muneharu; Shigeoka, Yasushi; Suzuki, Masato; Taguchi, Tetsuya; Kubota, Tomoyuki; Akazawa, Kouhei; Kohno, Norio

    2015-01-01

    Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT). Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2), followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug. This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and

  14. The curative effect of zoledronic acid and pamidronic acid on treating ostealgia in malignant tumor with bone metastases and its side effects on serum calcium and phosphorus*%双膦酸盐对骨转移癌骨痛治疗及血清钙磷影响

    Institute of Scientific and Technical Information of China (English)

    Yuedi Dai; Meixing Wang; Li Tao; Anqi Li; Haixia Wu; Mi Xiao

    2011-01-01

    Objective: Bisphosphonates were widely used with the rate of malignant tumor with bone metastases increasing rapidly. The aim of this study was to evaluate zoledronic acid and pamidronic acid on treating ostealgia of malignant tumor with bone metastases and serum calcium, phosphorus and alkaline phosphorus movement. Methods: One Hundred cancer patients with bone metastases were diagnosed according to pathological and imaging methods. After zoledronic acid or pamidronic acid intravenous infusion one and two months, ostealgia degree, serum calcium, serum phosphorus and alkaline phosphorus were observed before bisphosphonates treatment, one and two months after treatment, respectively. Results:Ostealgia degree did not change significantly after diphosphonates treatment from one to two months (P > 0.05). The linear correlation between serum calcium and serum phosphorus on bone metastases cancer patients before therapy was dismissed after bisphosphonates treatment one month and did not recover in two months. The incidence of hypo-calcium after diphosphonate treatment one month (54%) and two months (56%) were significantly increased than that before treatment (36%) (x2 = 6.55, P = 0.011; x2 = 8.05, P = 0.005). Serum calcium and serum phosphorus were both decreased after treatment one month (t = 4.39, P = 0.000; t = 2.50, P = 0.014) and two months (t = 4.32, P = 0.000; t = 2.49, P = 0.010). There had no difference between zoledronic acid and pamidronic acid on treating of ostealgia and serum calcium and phosphorus changing.Conclusion: Zoledronic acid and pamidronic acid can relief ostealgia of cancer patients with bone metastases and induce hypo-calcium, break the linear relationship between calcium and phosphorus. There have no difference between zoledronic acid and pamidronic acid on treating ostealgia and inducing hypo-calcium and hypo-phosphorus.

  15. Maximizing bone formation in posterior spine fusion using rhBMP-2 and zoledronic acid in wild type and NF1 deficient mice.

    Science.gov (United States)

    Bobyn, Justin; Rasch, Anton; Kathy, Mikulec; Little, David G; Schindeler, Aaron

    2014-08-01

    Spinal pseudarthrosis is a well described complication of spine fusion surgery in NF1 patients. Reduced bone formation and excessive resorption have been described in NF1 and anti-resorptive agents may be advantageous in these individuals. In this study, 16 wild type and 16 Nf1(+/-) mice were subjected to posterolateral fusion using collagen sponges containing 5 µg rhBMP-2 introduced bilaterally. Mice were dosed twice weekly with 0.02 mg/kg zoledronic acid (ZA) or sterile saline. The fusion mass was assessed for bone volume (BV) and bone mineral density (BMD) by microCT. Co-treatment using rhBMP-2 and ZA produced a significant increase (p Nf1(+/-) mice (+174%). Co-treatment also produced a significantly higher total BMD of the fusion mass compared to rhBMP-2 alone in both groups (p Nf1(+/-) deficient mice still generated less bone than wild type controls. TRAP staining on histological sections indicated an increased osteoclast surface/bone surface (Oc.S/BS) in Nf1(+/-) mice relative to wild type mice, and this was reduced with ZA treatment.

  16. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2014-07-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  17. Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

    Science.gov (United States)

    Martin, C K; Dirksen, W P; Carlton, M M; Lanigan, L G; Pillai, S P; Werbeck, J L; Simmons, J K; Hildreth, B E; London, C A; Toribio, R E; Rosol, T J

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

  18. 唑来膦酸注射液治疗老年骨质疏松症患者的药物经济学分析%Pharmacoeconomic Analysis of Zoledronic Acid Injection Treatment in Elderly Patients with Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    范洪春

    2015-01-01

    目的 探讨鲑鱼降钙素鼻喷剂与唑来膦酸注射液治疗老年骨质疏松症患者的成本-效果药物经济学.方法 选取2013年6月至2014年8月200例老年骨质疏松症患者,将患者分为试验组(100例)和对照组(100例),分别应用唑来膦酸注射液、鲑鱼降钙素鼻喷剂治疗,比较其疗效,并进行成本-效果分析.结果 试验组患者治疗总有效率、成本-效果比优于对照组,差异均有统计学意义(均P<0.05).结论 唑来膦酸注射液治疗老年骨质疏松症疗效佳,成本-效果优.%Objective To explore the effect of Calcitonin Salmon calcitonin nasal spray and actual Zoledronic Acid Injection treatment in elderly patients with osteoporosis,and pharmacoeconomic analysis.Methods From 2013 June to 2014 August 200 cases of elderly patients with osteoporosis,the patients were divided into test group and control group of 100 cases and 100 cases,respectively,the application of Zoledronic Acid Injection,Salmon Calcitonin Nasal Spray treatment,compared the efficacy and cost-effectiveness analysis.Results Results in the test group,the total efficiency of treatment cost is better than the control group,the difference was statisticaly significant(P<0.05). Conclusion Zoledronic Acid Injection treatment of senile osteoporosis effect of good,cost-effective advantages.

  19. Clinical safety observation of zoledronic acid treatment for senile primary osteoporosis%唑来膦酸治疗老年原发性骨质疏松症的临床安全性观察

    Institute of Scientific and Technical Information of China (English)

    郝杰; 胡侦明; 张晓军; 江维; 沈皆亮

    2013-01-01

    目的 探讨临床应用唑来膦酸静脉滴注治疗老年原发性骨质疏松症的安全性和依从性.方法 观察首次静脉滴注唑来膦酸治疗50例原发性骨质疏松症患者的一般情况和副反应,询问患者是否愿意接受第二次治疗.结果 所有患者在滴注过程中均无严重不良反应发生,但24%患者在输注后3d内出现了急性一过性不良反应,包括发热、关节痛、肌痛、流感样症状、头痛等,绝大多数患者同意继续使用.结论 唑来膦酸治疗原发性骨质疏松症安全性较高,依从性好,是一种较理想的治疗新选择,其疗效有待于长期随访.%Objective To investigate the safety and compliance of zoledronic acid, which was clinically used through intravenous injection, for the treatment of senile primary osteoporosis. Methods A total of 50 patients with primary osteoporosis who were treated with zoledronic acid intravenously for the first-time were enrolled. General condition and adverse reaction of all the patients were observed. Their willing about whether to receive the 2nd treatment or not was inquired. Results None of 50 patients had severe adverse reaction during the process of intravenous injection. Whereas 24% patients had acute and temporary adverse reaction, including fever, joint pain, myosalgia, influenza-like symptom, and headache in the first 3 days after intravenously injection. Most patients agreed to use zoledronic acid for the treatment continually. Conclusion The safety of zoledronic acid for the treatment of primary osteoporosis is high, and the compliance is good. The treatment is a new ideal choice, but the clinical effect needs long-term follow-up.

  20. Enhanced anti-tumor effect of zoledronic acid combined with temozolomide against human malignant glioma cell expressing O6-methylguanine DNA methyltransferase.

    Directory of Open Access Journals (Sweden)

    Junya Fukai

    Full Text Available Temozolomide (TMZ, a DNA methylating agent, is widely used in the adjuvant treatment of malignant gliomas. O6-methylguanine-DNA methyltranferase (MGMT, a DNA repair enzyme, is frequently discussed as the main factor that limits the efficacy of TMZ. Zoledronic acid (ZOL, which is clinically applied to treat cancer-induced bone diseases, appears to possess direct anti-tumor activity through apoptosis induction by inhibiting mevalonate pathway and prenylation of intracellular small G proteins. In this study, we evaluated whether ZOL can be effectively used as an adjuvant to TMZ in human malignant glioma cells that express MGMT. Malignant glioma cell lines, in which the expression of MGMT was detected, did not exhibit growth inhibition by TMZ even at a longer exposure. However, combination experiment of TMZ plus ZOL revealed that a supra-additive effect resulted in a significant decrease in cell growth. In combined TMZ/ZOL treatment, an increased apoptotic rate was apparent and significant activation of caspase-3 and cleavage of poly-(ADP-ribose polymerase were observed compared with each single drug exposure. There were decreased amounts of Ras-GTP, MAPK and Akt phosphorylation and MGMT expression in the ZOL-treated cells. Subcutanous xenograft models showed significant decrease of tumor growth with combined TMZ/ZOL treatment. These results suggest that ZOL efficaciously inhibits activity of Ras in malignant glioma cells and potentiates TMZ-mediated cytotoxicity, inducing growth inhibition and apoptosis of malignant glioma cells that express MGMT and resistant to TMZ. Based on this work, combination of TMZ with ZOL might be a potential therapy in malignant gliomas that receive less therapeutic effects of TMZ due to cell resistance.

  1. Gamma-delta T lymphocytes and 25-hydroxy vitamin D levels as key factors in autoimmunity and inflammation: the case of zoledronic acid-induced acute phase reaction.

    Science.gov (United States)

    De Santis, M; Cavaciocchi, F; Ceribelli, A; Crotti, C; Generali, E; Fabbriciani, G; Selmi, C; Massarotti, M

    2015-04-01

    Zoledronic acid (ZA) infusion for osteoporosis is frequently associated with the onset of an acute phase reaction (APR) secondary to the activation of γδ T cell receptor (TCR) lymphocytes (γδ T cells) and to low vitamin D levels, similar to what is observed in chronic inflammation and autoimmunity. In this study we investigated whether the phenotype of γδ T cells is associated with APR and 25-OH vitamin D (25-OHvD) levels. For flow-cytometry analysis, peripheral blood samples were obtained from 52 osteoporotic women prior to 5 mg ZA intravenous infusion and from nine women (five with APR) one week later. Twenty-six/52 (50%) patients reported APR and APR+ cases had a higher percentage of central memory Th1-like γδ T cells. One week after ZA infusion, APR was associated with a decreased percentage of central memory Th1-like γδ T cells, an increase in the percentage and activation of effector memory Th1-like γδ T cells, and an increase in Th17-like γδ T cells. Lower 25-OHvD levels were significantly associated with APR, but no correlation was found between 25-OHvD level and γδ T cell percentage or subsets. In conclusion, patients experiencing APR related to ZA infusion have lower 25-OHvD levels and we suggest that the higher percentage of central memory Th1-like γδ T cells and the expansion of effector memory Th1-like and Th17-like γδ T cells are associated with the occurrence of APR.

  2. Comparison of neurotropic effects of L-glutamic acid and its new derivative β-phenylglutamic acid hydrochloride (RGPU-135, glutarone).

    Science.gov (United States)

    Tyurenkov, I N; Bagmetova, V V; Chernysheva, Yu V; Merkushenkova, O V

    2014-04-01

    In contrast to L-glutamic acid (200 mg/kg), β-phenylglutamic acid hydrochloride (26 mg/kg) produces no anticonvulsant effects during generalized convulsions induced by "maximum electric shock". However, β-phenylglutamic acid hydrochloride was more potent than L-glutamic acid in increasing survival rate, promoting recovery of spontaneous motor activity, and maintainance locomotor and exploratory activity in the open field test and cognitive functions in conditioned passive avoidance test, i.e. exhibited neuroprotective activity. This substance did not change the threshold of pain induced by electric stimulation of paws (up to vocalization) and thermal tail stimulation (tail-flick), whereas L-glutamic acid decreased this parameter. β-Phenylglutamic acid suppressed aggression in the test for provoked unmotivated aggression, while L-glutamic acid enhanced it. Due to these neurotropic effects, β-phenylglutamic acid hydrochloride can be used as the basis for the development of drugs with antidepressant, anxiolytic, and neuroprotective actions.

  3. Hydroxylamine hydrochloride-acetic acid-soluble and -insoluble fractions of pelagic sediment: Readsorption revisited

    Science.gov (United States)

    Piper, D.Z.; Wandless, G.A.

    1992-01-01

    The extraction of the rare earth elements (REE) from deep-ocean pelagic sediment, using hydroxylamine hydrochloride-acetic acid, leads to the separation of approximately 70% of the bulk REE content into the soluble fraction and 30% into the insoluble fraction. The REE pattern of the soluble fraction, i.e., the content of REE normalized to average shale on an element-by-element basis and plotted against atomic number, resembles the pattern for seawater, whereas the pattern, as well as the absolute concentrations, in the insoluble fraction resembles the North American shale composite. These results preclude significant readsorption of the REE by the insoluble phases during the leaching procedure.

  4. 唑来膦酸治疗女性绝经后骨质疏松所致急性发热临床分析%Analysis of acute fever reaction in postmenopausal women with zoledronic acid treatment for osteoporosis

    Institute of Scientific and Technical Information of China (English)

    杨毅; 刘丽梅; 李蓬秋; 鲜杨; 张学军; 包明晶; 张磊; 杨艳; 朱显军; 曹旭

    2013-01-01

    Objective To analyze the incidence of acute fever reaction after the treatment of intravenous zoledronic acid in postmenopausal women with osteoporosis, and to identify the related factors. Methods Clinical data of 63 postmenopausal women with osteoporosis, who were treated with intravenous infusion of 5mg zoledronic acid from June 2010 to April 2012, were analyzed retrospectively. The incidence of acute fever reaction in these patients was observed. All the patients were divided into fever group and non-fever group according to whether having fever symptoms or not. The age, severity of osteoporosis before zoledronic acid treatment, variations of parathyroid hormone and serum calcium, and the use of anti-osteoporosis drugs before the treatment were compared between the 2 groups. Results Twenty-one patients had acute fever reaction ( 33.3% ). Among these 21 patients, 71% patients ( 15/21 ) had fever on the day of zoledronic acid treatment, and the other patients had fever on the first day after the treatment. The fever lasted for 1 day in 66. 7% of the patients ( 14/21 ), and for 2 days in 5 patients. The average temperature was 38. 8 ±0.5 C. The patients with fever had higher parathyroid hormone level before treatment than those without fever ( P <0.05 ). Serum calcium and bone mineral density showed no significant difference between the 2 groups. Conclusion Acute fever reaction is not rare in postmenopausal patients receiving intravenous zoledronic acid for the treatment of osteoporosis, but it is transient. Parathyroid hormone level before the treatment is associated with the fever.%目的 分析静脉用唑来膦酸治疗女性绝经后骨质疏松患者引起的急性发热反应及其相关因素.方法 回顾性分析我科2010年6月至2012年4月使用静脉用唑来膦酸5mg治疗的绝经后骨质疏松患者共63人.观察急性期发热出现比例.按是否出现发热症状分为发热组与无发热组.比较两组患者年龄、静脉用唑来膦

  5. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    Science.gov (United States)

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  6. Spectrophotometric determination of procaine hydrochloride in pharmaceutical products using 1,2-naphthoquinone-4-sulfonic acid as the chromogenic reagent

    Science.gov (United States)

    Xu, Li Xiao; Shen, Yun Xiu; Wang, Huai You; Jiang, Ji Gang; Xiao, Yan

    2003-11-01

    Spectrophotometric determination of procaine hydrochloride is described. The procaine hydrochloride reacts with 1,2-naphthoquinone-4-sulfonic acid in pH 3.60 buffer solution to form a salmon pink compound, and its maximum absorption wavelength is at 484 nm, ɛ 484=5.22×10 3.The absorbance for procaine hydrochloride from 0.30 to 100 μg ml -1 obeys Beer's law. The linear regression equation of the calibration graph is C=19.23A-0.03, with a linear regression correlative coefficient is 0.9996, the detection limit is 0.28 μg ml -1; recovery is from 98.0 to 105.2%. Effects of pH, surfactant, organic solvent, foreign ions, and standing time on the determination of procaine hydrochloride have been examined. This method is rapid and simple, and can be used for the determination of procaine hydrochloride in injection solution of procaine hydrochloride. The results obtained by this method agreed with those by the official method (dead-stop titration).

  7. Research Progress on Antitumor Effects of Zoledronic Acid%唑来膦酸抗肿瘤作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘俊彦

    2012-01-01

    唑来膦酸作为第三代双膦酸盐药物已广泛用于恶性实体瘤骨转移相关事件的防治.进一步研究发现,唑来膦酸可通过抑制甲羟戊酸途径中焦磷酸合酶的活性,使异戊烯焦磷酸大量蓄积,同时异戊烯焦磷酸与细胞内一磷酸腺苷结合形成三磷酸腺苷分解类似物蓄积于细胞中,从而改变细胞周期蛋白和凋亡蛋白水平,抑制肿瘤细胞生长并促进其凋亡,具有一定的直接和/或间接抗肿瘤作用.有关肺癌、乳腺癌、前列腺癌及肝癌等前期临床试验提示唑来膦酸与细胞毒药物、内分泌药物及靶向药物联合具有一定程度的协同抗肿瘤作用,并且在抗肿瘤药物之后序贯应用效果更好.一些相关的临床试验正在进行中.%Zoledronic acid (ZOL), a third-generation bisphosphonate, has been widely used for the treatment of skeletal-related events in malignant solid tumors. Previous studies have demonstrated that ZOL can induce direct and indirect antitumor activities through py-rophosphate synthase inhibition, which blocks the mevalonate pathway and causes isopentenyl pyrophosphate ( IPP ) accumulation. IPP becomes conjugated to AMP to form a novel ATP analog. The amount of IPP and ATP analog is correlated with cyclin and apoptotic protein levels, which are associated with cell line growth and apoptosis. Preclinical studies on lung cancer, breast cancer, prostate cancer, liver cancer, and so on, confirmed a synergistic effect between ZOL and cytotoxic, endocrine, and targeted drugs. The observed improvement in antitumor effects by using combination therapy with ZOL is currently being verified through additional clinical trials.

  8. Oxidation of Tetracaine Hydrochloride by Chloramine-B in Acid Medium: Kinetic Modeling

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    Jayachamarajapura Pranesh Shubha

    2014-01-01

    Full Text Available Tetracaine hydrochloride (TCH is one of the potent local anaesthetics. A kinetic study of oxidation of tetracaine hydrochloride by sodium N-chlorobenzenesulfonamide (chloramine-B or CAB has been carried in HClO4 medium at 303 K. The rate shows first-order dependence on [CAB]o, shows fractional–order dependence on [substrate]o, and is self-governing on acid concentration. Decrease of dielectric constant of the medium, by adding methanol, increased the rate. Variation of ionic strength and addition of benzenesulfonamide or NaCl have no significant effect on the rate. The reaction was studied at different temperatures and the activation parameters have been evaluated. The stoichiometry of the reaction was found to be 1 : 5 and the oxidation products were identified by spectral analysis. The conjugate free acid C6H5SO2NHCl of CAB is postulated as the reactive oxidizing species. The observed results have been explained by plausible mechanism and the related rate law has been deduced.

  9. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic Acid in combined dosage forms.

    Science.gov (United States)

    Pathak, A; Rajput, S J

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  10. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic acid in combined dosage forms

    Directory of Open Access Journals (Sweden)

    Pathak A

    2008-01-01

    Full Text Available Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot′s method were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 µg/ml, 1-40 µg/ml and 1-30 µg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  11. Ivabradine Hydrochloride (S-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation

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    Veronika Sládková

    2017-01-01

    Full Text Available The pharmaceutical salt ivabradine hydrochloride is indicated for the symptomatic treatment of chronic stable angina pectoris and chronic heart failure. It exhibits extensive polymorphism and co-crystallization, which could be a way to provide an alternative solid form. We conducted a co-crystal screen, from which two hits were identified: with (S-mandelic and (R-mandelic acid. Both structures were determined from single-crystal X-ray diffraction data as co-crystals. The co-crystals were further characterized by common solid-state techniques, such as X-ray powder diffraction (XRPD, differential scanning calorimetry (DSC, solid-state NMR, IR and Raman spectroscopy, and dynamic vapor sorption (DVS. The co-crystal with (S-mandelic acid was selected for further development; its physical and chemical stability was compared with two different polymorphs of the hydrochloride salt. The co-crystal exhibited a similar stability with the polymorph used in the original drug product and was, therefore, selected for formulation into the drug product. During the pre-formulation experiments, the in situ formation of the co-crystal was achieved during the wet granulation process. The following formulation experiments showed no influence of in situ prepared co-crystal on the overall stability of the bulk, when compared with pre-prepared co-crystal formulation.

  12. Synthesis, crystal structure and antitumor effect of a novel copper(II) complex bearing zoledronic acid derivative.

    Science.gov (United States)

    Qiu, Ling; Lv, Gaochao; Guo, Liubin; Chen, Liping; Luo, Shineng; Zou, Meifen; Lin, Jianguo

    2015-01-07

    A great majority of Cu(II) complexes currently studied in the anticancer research field exert their antiproliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu3(ZL)2(H2O)6]·6H2O}n (1) (ZL = 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)2]·3H2O (2) (IPrDP = 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid). Due to the insolubility of polymer 1 in common solvents, only the biological activities of complex 2 were investigated. The antitumor activity of complex 2 was evaluated against a panel of human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. Complex 2 exhibited comparable cytotoxic effect to cisplatin (CDDP) against the human colon carcinoma cells HCT116, and superior selectivity for inhibiting human hepatocarcinoma cells rather than normal liver cells. The cell cycle distribution analysis indicates that complex 2 inhibits human carcinoma cells by inducing the cell cycle arrest at the G2/M phase, showing a similar mechanism of action to that of CDDP. The binding interaction of complex 2 with calf thymus DNA (CT-DNA) has been explored by UV-vis absorption and circular dichroism (CD), demonstrating complex 2 has a moderate binding affinity for DNA through intercalation.

  13. One case of influenza-like adverse reaction induced by zoledronic acid injection%唑来膦酸注射液致流感样不良反应1例

    Institute of Scientific and Technical Information of China (English)

    李铮

    2011-01-01

    1 例老年女性患者应用唑来膦酸注射液治疗骨质疏松症,出现了恶心、呕吐、心悸等流感样症状及白细胞的异常升高,未见其他感染,4 d 后体温逐步恢复正常水平.%An old female patient experienced an abnormal increase in WBC and influenza-like symptoms,including nausea, vomiting and cardiopalmus, after administration of zoledronic acid injection for osteoporosis treatment. No infections were found, and the body temperature gradually recovered to normal level 4 days later.

  14. Effect of zoledronic acid on bone mass in osteoporotic patients%唑来膦酸对骨质疏松骨含量的影响

    Institute of Scientific and Technical Information of China (English)

    高雷; 任艳; 高华增

    2015-01-01

    Objective To explore the influence of bisphosphonates in bone mass in osteoporosis. Methods Fifty⁃nine patients with postmenopausal osteoporosis were selected and were randomly divided into treatment group ( n=30 ) and control group ( n=29). In treatment group, patients received intravenous 5mg zoledronic acid (Aclasta) injection once, and continued with 0�9%normal saline 100ml and calcium gluconate 10 ml (1g) once a day for 3-5 days. They also took calcium carbonate 600mg/d and active vitamin D3 400 iu/d. In control group, patients were given oral calcium 600 mg/d and active vitamin D3 400 iu/d. The efficacy was evaluated after 6 months. Results After the treatment, BMD of patients increased in varying degree. Bone mineral content was elevated significantly. The pain decreased significantly. The difference was statistically significant ( P < 0�05 ) compared with that before treatment. No osteoporotic fractures occurred during the follow⁃up. Conclusion Bisphosphonates combining with calcium can significantly relieve the pain symptom, improve and maintain the BMD level, increase bone mass and reduce the incidence of osteoporotic fractures in the treatment of postmenopausal osteoporosis. It is a safe and effective method for treatment of postmenopausal osteoporosis.%目的:探讨双膦酸盐对骨质疏松骨量的影响。方法选绝经后骨质疏松症患者59例,随机分为治疗组和对照组,其中治疗组(30例),一次性静脉滴注唑来膦酸注射液5 mg,后次日始日一次静点0�9%生理盐水100 ml+葡萄糖酸钙10 ml(1g)3~5天,同时碳酸钙600 mg/d,活性维生素D3400IU/d口服;对照组(29例),给予同剂量的碳酸钙及活性维生素D3口服,6个月后复查评价疗效。结果患者临床疗效比较,治疗后患者BMD值有不同程度增高,其中骨含量一项升高明显,疼痛感明显下降,与治疗前比较,差异有统计学意义(P<0�05),随访期间

  15. Revisión de las implicaciones clínicas del ácido zoledrónico en el tratamiento del dolor Clinical implications of zoledronic acid for the treatment of pain

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    M. A. Vidal

    2006-11-01

    tiempo de perfusión, aumentando al aumentar la velocidad de perfusión. Estudios in vitro e in vivo han demostrado que la tolerabilidad renal del ácido zoledrónico es mayor que la del pamidronato. En los ensayos clínicos en pacientes con metástasis óseas e hipercalcemia de origen tumoral, el ácido zoledrónico presentó un perfil de seguridad aceptable. Los acontecimientos adversos comunicados con más frecuencia fueron: síndrome seudogripal, reacciones gastrointestinales, anemia, debilidad, tos, disnea y edema. Coste efectividad: El costo económico de las complicaciones esqueléticas relacionadas con la neoplasia es muy elevado, contribuyendo al incremento del coste la radioterapia ósea y el ingreso hospitalario. No obstante existe una gran variabilidad de los costos en pacientes con cáncer en estadio avanzado, lo que dificulta la obtención de resultados. Discusión: Teniendo en cuenta la evidencia existente de la actividad antitumoral que posee el ácido zoledrónico, debemos centrarnos en el conocimiento de los mecanismos implicados y poder determinar la dosis más efectiva para poder maximizar este potencial efecto antitumoral. Los objetivos que debemos plantearnos ahora ante un paciente diagnosticado de metástasis ósea, se basan en establecer el momento adecuado de inicio de tratamiento con ácido zoledrónico así como la duración del mismo en función de la respuesta terapéutica.Introduction: Bone approximately represents 40% of cancer recurrences , with a higher incidence in patients with múltiple myeloma, breast, lung and prostate cancer. Bone pain is the most frequent and considerably affects patients´ life quality. Although resolution is not possible, symptom control is. Biphosphonates are powerful inhibitors of normal and pathological bone resorption and have an important effect on bone metastasis. Zoledronic acid is the most frequently used biphosphonate for this purpose. It has been approved for the prevention of complications related to

  16. ABSORPTION RATIO METHOD FOR ESTIMATION OF DROTAVERINE HYDROCHLORIDE AND MEFENAMIC ACID IN THEIR COMBINED TABLET DOSAGE FORM

    OpenAIRE

    Sakhare Ram Suresh; Jamkhande Prasad Govindrao

    2012-01-01

    A new, simple, accurate and sensitive UV-spectrophotometric absorption Ratio method has been developed for simultaneous determination of Drotaverine Hydrochloride and Mefenamic Acid in their combined Tablet dosage form. The method is based upon determination of Drotaverine HCl and Mefenamic Acid at 239 nm, and 280nm in Methanol. Drotaverine HCl and Mefenamic Acid at isoabsorptive λmax 239 nm and at 280 nm λmax Mefenamic acid shows linearity in the concentration range of 3-30 μg/ml and 3 -30...

  17. ABSORPTION RATIO METHOD FOR ESTIMATION OF DROTAVERINE HYDROCHLORIDE AND MEFENAMIC ACID IN THEIR COMBINED TABLET DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Sakhare Ram Suresh

    2012-10-01

    Full Text Available A new, simple, accurate and sensitive UV-spectrophotometric absorption Ratio method has been developed for simultaneous determination of Drotaverine Hydrochloride and Mefenamic Acid in their combined Tablet dosage form. The method is based upon determination of Drotaverine HCl and Mefenamic Acid at 239 nm, and 280nm in Methanol. Drotaverine HCl and Mefenamic Acid at isoabsorptive λmax 239 nm and at 280 nm λmax Mefenamic acid shows linearity in the concentration range of 3-30 μg/ml and 3 -30 μg/ml respectively. The method was validated statistically.

  18. Development and validation of a liquid chromatographic method for estimation of dicyclomine hydrochloride, mefenamic Acid and paracetamol in tablets.

    Science.gov (United States)

    Shah, D A; Rana, Jainika P; Chhalotiya, Usmangani K; Baldania, S L; Bhatt, K K

    2014-01-01

    Liquid chromatographic method was developed for simultaneous quantitative determination of dicyclomine hydrochloride, mefenamic acid and paracetamol in their combined dosage form. The separation was achieved using a C18 column (250×4.6 mm id, 5 μm) using acetonitrile:20 mM potassium dihydrogen phosphate 70:30 (v/v) adjusted to pH 4 using orthophosphoric acid as mobile phase at a flow rate of 1 ml/min and detection at 220 nm. Separation was completed within 12 min. The retention times of dicyclomine hydrochloride, mefenamic acid and paracetamol were 3.8, 9.3 and 2.5 minutes respectively. The proposed method was found to have linearity in concentration range of 10-100 μg/ml for dicyclomine hydrochloride, 0.05-10 μg/ml for mefenamic acid and 0.1-20 μg/ml for paracetamol. The developed method has been statistically validated and was found to be simple, precise, reproducible and accurate. The developed and validated method was successfully used for the quantitative analysis of commercially available dosage form.

  19. Spectrophotometric Determination of Gemifloxacin Mesylate, Moxifloxacin Hydrochloride, and Enrofloxacin in Pharmaceutical Formulations Using Acid Dyes

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    Ayman A. Gouda

    2014-01-01

    Full Text Available Simple, rapid, and extractive spectrophotometric methods were developed for the determination of some fluoroquinolones antibiotics: gemifloxacin mesylate (GMF, moxifloxacin hydrochloride (MXF, and enrofloxacin (ENF in pure forms and pharmaceutical formulations. These methods are based on the formation of ion-pair complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG, bromocresol purple (BCP, bromophenol blue (BPB, bromothymol blue (BTB, and methyl orange (MO in acidic buffer solutions. The formed complexes were extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG, BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and BTB, respectively, in case of ENF. The analytical parameters and their effects are investigated. Beer’s law was obeyed in the ranges 1.0–30, 1.0–20, and 2.0–24 μg mL−1 for GMF, MXF, and ENF, respectively. The proposed methods have been applied successfully for the analysis of the studied drugs in pure forms and pharmaceutical formulations. Statistical comparison of the results with the reference methods showed excellent agreement and indicated no significant difference in accuracy and precision.

  20. Effect of Zoledronic Acid on the Healing of Distal Radial Fracture%唑来膦酸对老年桡骨远端骨折术后疗效观察

    Institute of Scientific and Technical Information of China (English)

    尹自龙; 石磊; 王林; 刘驰; 郑念野; 纪泉; 张华俦; 良元; 薛庆云

    2014-01-01

    目的:观察唑来膦酸对老年桡骨远端骨折的术后疗效。方法分析自2012年1月1日至2012年12月31日行桡骨远端骨折手术患者136例接受手术治疗并纳入研究,118例获得随访(87%),分成唑来膦酸组(A 组,59例)和对照组(B 组,59例)。唑来膦酸组平均年龄(73.09±5.04)岁,男12例,女47例,术后2~7 d 使用唑来膦酸抗骨质疏松治疗,并常规补充钙剂和骨化三醇;对照组平均年龄(73.25±6.96)岁,男14例,女45例,术后2~7 d 使用针剂密盖息抗骨质疏松治疗,出院后继续使用密盖息鼻喷剂至术后3个月,常规补充钙剂和骨化三醇,术后4周、3个月随访骨折愈合的情况及术后1年复查骨密度的情况。结果老年桡骨远端骨折患者使用唑来膦酸抗骨质疏松药物后骨折愈合无明显影响且腕关节功能改善,术后1年骨密度较前增加。结论发生桡骨远端骨折的老年骨质疏松患者使用唑来膦酸药物后骨质疏松治疗效果好,同时对骨质疏松性桡骨远端愈合无明显不利影响。%Objective To observe the effect of zoledronic acid on distal radius fractures in elderly patients after operation. Methods Analysis of 136 cases of distal radius fractures underwent operation in our hospital from January 1,2012 to Decem-ber 31,2012,118 patients were followed up(87% ),Patients were divided into zoledronic acid group(group A,59 patients) and control group(group B,59 patients),group A with an average age of 73. 09 ± 5. 04,12 male patients,47 female patients, postoperative second to seventh day with anti osteoporosis treatment of zoledronic acid,and a conventional calcium and calcitri-ol supplement,B group with an average age of 73. 25 ± 6. 96,male 14 patients,female patient 45,postoperative second to sev-enth day with anti osteoporosis treatment of Injection of Miacalcic,continue using of Miacalcic nasal spray from discharge to postoperative 3 months

  1. 唑来膦酸在骨质疏松患者中的应用及疗效%Efficacy and application of zoledronic acid in the treatment of osteoporosis

    Institute of Scientific and Technical Information of China (English)

    段鹏; 涂萍; 吴和平; 丁浔; 肖魏华; 邓波

    2014-01-01

    Objective To observe the safety and efficacy of intravenous infusion of zoledronic acid ( 5 mg/100 ml ) in the treatment of primary osteoporosis and type 2 diabetes combined with osteoporosis.Methods Forty-six patients with osteoporosis, who were treated in our hospital, were selected.Among all the patients, 25 patients were divided into primary osteoporosis group, and 21 patients were divided into type 2 diabetes combined with osteoporosis group.Physical examination was performed, and the body mass index ( BMI ) was calculated.Serum glucose was detected using glucose oxidase method.The bone mineral density ( BMD) of the lumbar vertebrae ( L2-L4 ) and the left femoral neck was detected using dual energy X-ray absorptiometry ( DXA) . All the patients were treated with intravenous infusion of zoledronic acid.The adverse effect was monitored.One year later, BMD was re-detected, and the change of BMD after the treatment was also observed.Results No significant difference of age, BMI, and BMD of the lumbar vertebrae and the left femoral neck between the two groups was observed (P>0.05).After the intravenous infusion of zoledronic acid, the adverse effect including fever, acratia, headache, arthralgia, and nausea was observed in both groups.Seven patients in type 2 diabetes combined with osteoporosis group showed a transient increase of blood glucose, but all the symptoms disappeared and blood glucose returned to normal in 3 days.After 1-year treatment with zoledronic acid, BMD of the lumbar vertebrae and the left femoral neck in primary osteoporosis group increased by 4.27% and 4.11%, respectively, which increased by 3.42% and 3.26% in type 2 diabetes combined with osteoporosis group, respectively.BMD in both groups was significant higher than that before the treatment (P0.05).Conclusion Zoledronic acid can increase BMD in patients with osteoporosis.And it has a good efficacy for the patients with primary osteoporosis or type 2 diabetes combined with osteoporosis.%

  2. Efeito do ácido zoledrônico em tíbias de ratas ooforectomizadas: estudo prospectivo e randomizado Effects of zoledronic acid on ooforectomized rats' tibiae: a prospective and randomized study

    Directory of Open Access Journals (Sweden)

    Fernando Roberto Alves Pereira

    2009-02-01

    Full Text Available OBJETIVO: Investigar as repercussões clínicas, biomecânicas e histomorfométricas do ácido zoledrônico em tíbias de ratas osteoporóticas, após ooforectomia bilateral. MÉTODOS: Foram estudadas, prospectivamente, 40 ratas da linhagem Wistar (Rattus novergicus albinus. Com 60 dias de vida, os animais foram aleatorizados em dois grupos de acordo com o procedimento cirúrgico: ooforectomia bilateral (O (n=20 e pseudo-cirurgia ("sham" (P (n=20. Após 30 dias, os animais foram divididos em quatro subgrupos, de acordo com a administração de 0,1mg/kg de ácido zoledrônico (AZ ou água destilada (AD: OAZ (n=10, OAD (n=10, PAZ (n=10 e PAD (n=10. Após 12 meses, os animais foram eutanasiados e suas tíbias analisadas. No estudo clínico foi considerado o peso dos animais; no estudo biomecânico foram realizados ensaios compressivos e na análise histomorfométrica foi determinada a área trabecular óssea. RESULTADOS: Os grupos "O" tiveram aumento de peso significativamente maior que os grupos "P" (p=0,005. Os grupos OAZ e PAZ tiveram aumento, não significativo, de peso quando comparados aos grupos OAD (p=0,47 e PAD (p=0,68. Os grupos com ácido zoledrônico e com água destilada suportaram carga máxima, semelhante (p=0,2, no momento em que ocorreu fratura. Nos grupos com ácido zoledrônico verificou-se o aumento não significante da área trabecular óssea quando comparados aos grupos com água destilada (p=0,21. Houve correlação positiva entre a área trabecular e a carga máxima (p=0,04; r=0,95. CONCLUSÃO: O ácido zoledrônico não influiu significativamente no peso dos animais. Os resultados mostraram aumento, não significante, tanto da resistência óssea diafisária tibial, como da área trabecular óssea.OBJECTIVE: To investigate clinical, biomechanic and histomorphometric effects of zoledronic acid on osteoporotic rats'tibiae after bilateral ooforectomy. METHODS: 40 female Wistar (Rattus novergicus albinus rats were prospectively

  3. Observation of the Effect for Elderly Women's Osteoporosis Using Zoledronic Acid Combination%唑来膦酸联合用药治疗老年女性骨质疏松患者的疗效观察

    Institute of Scientific and Technical Information of China (English)

    郑彬彬; 叶曼; 李晓静

    2013-01-01

    OBJECTIVE To investigate the effect of zoledronic acid combinated salmon calcitonin see calcimar,Caltrate D,alfacalcidol and bone-peptide injection cure old osteoporosis.METHODS Forty cases of thoracolumbar pain of osteoporosis patients were randomly divided into two groups:The control group received salmon calcitonin see calcimar,Caltrate D,alfacalcidol,the therapeutic group received zoledronic acid and bone-peptide injection besides salmon calcitonin see calcimar,Caltrate D,calcitonin.The two groups received six months therapia.Observe the BMD and pain before and after the therapy.RESULTS The BMD of two groups both rised(P<0.05).The BMD of therapeutic group is higher than the control (P<0.05).The VAS score of two groups both descend(P<0.05).The VAS score of therapeutic group is lower than the control (P<0.05).CONCLUSION Zoledronic acid combinated salmon calcitonin see calcimar,Caltrate D,alfacalcidol and bone-peptide injection is a safe curation for old osteoporosis,and more effective than the curation used salmon calcitonin see calcimar,Caltrate D and alfacalcidol together.%目的 探讨唑来膦酸及鲑鱼降钙素联合钙尔奇D、阿法骨化醇、复方骨肽注射液治疗老年女性骨质疏松症的疗效.方法 选取40例老年女性骨质疏松性胸腰椎疼痛患者随机分为两组,对照组服用钙尔奇D片(钙尔奇D600)、阿法骨化醇,鲑鱼降钙素注射液、治疗组在对照组的基础上加用唑来磷酸注射液和复方骨肽注射液,两组均连续治疗半年,观察治疗前后的骨密度和疼痛变化.结果 两组治疗后骨密度均明显上升.与治疗前比较差异有统计学意义(P<0.05).治疗后治疗组骨密度明显高于对照组,差异有统计学意义(P<0.05).治疗后两组VAS评分均明显下降,与治疗前比较差异有统计学意义(P<0.05),治疗后治疗组VAS评分下降程度高于对照组,差异有统计学意义(P<0.05).结论 唑来膦酸及鲑鱼降钙素注射液联合

  4. Growth and properties of semi-organic nonlinear optical crystal: L-Glutamic acid hydrochloride

    Directory of Open Access Journals (Sweden)

    J. Uma

    2016-02-01

    Full Text Available Semiorganic nonlinear optical crystal of L-Glutamic acid hydrochloride (LGHC was grown from aqueous solution by slow evaporation technique. Single crystal X-ray Diffraction analysis confirms that LGHC crystallizes in orthorhombic system with noncentrosymmetric space group P212121. The powder X-ray diffraction study confirms the crystallinity of the grown crystal. The fundamental functional groups of the grown crystals were analyzed by Fourier Transform Infrared spectroscopic analysis in the range of 450–4000 cm−1. The range of optical transmission was ascertained using UV–vis–NIR studies. The Refractive Index of the LGHC crystal was found to be 1.4. The second harmonic generation efficiency of the LGHC was determined using Kurtz and Perry powder technique and it was 0.5 times greater than that of the KDP crystal. Thermo Gravimetric Analysis (TGA and Differential Thermal Analysis (DTA were used to study thermal behavior of the sample. The dielectric behavior and ac conductivity of the sample were studied as a function of frequency for different temperatures. The mechanical strength of the crystal was determined by Vicker׳s Hardness test. The elastic stiffness constant and yield strength of the sample was calculated.

  5. Growth and properties of semi-organic nonlinear optical crystal:L-Glutamic acid hydrochloride

    Institute of Scientific and Technical Information of China (English)

    J.Uma; V.Rajendran

    2016-01-01

    Semiorganic nonlinear optical crystal of L-Glutamic acid hydrochloride (LGHC) was grown from aqueous solution by slow evaporation technique. Single crystal X-ray Diffraction analysis confirms that LGHC crystallizes in orthorhombic system with noncentrosymmetric space group P212121. The powder X-ray diffraction study confirms the crystallinity of the grown crystal. The fundamental functional groups of the grown crystals were analyzed by Fourier Transform Infrared spectroscopic analysis in the range of 450–4000 cm¯1. The range of optical transmission was ascertained using UV–vis–NIR studies. The Refractive Index of the LGHC crystal was found to be 1.4. The second harmonic generation efficiency of the LGHC was determined using Kurtz and Perry powder technique and it was 0.5 times greater than that of the KDP crystal. Thermo Gravimetric Analysis (TGA) and Differential Thermal Analysis (DTA) were used to study thermal behavior of the sample. The dielectric behavior and ac conductivity of the sample were studied as a function of frequency for different temperatures. The mechanical strength of the crystal was determined by Vicker's Hardness test. The elastic stiffness constant and yield strength of the sample was calculated.

  6. New copper(II) complexes with dopamine hydrochloride and vanillymandelic acid: Spectroscopic and thermal characterization

    Science.gov (United States)

    Mohamed, Gehad G.; Nour El-Dien, F. A.; El-Nahas, R. G.

    2011-10-01

    The dopamine derivatives participate in the regulation of wide variety of physiological functions in the human body and in medication life. Increase and/or decrease in the concentration of dopamine in human body reflect an indication for diseases such as Schizophrenia and/or Parkinson diseases. The Cu(II) chelates with coupled products of dopamine hydrochloride (DO.HCl) and vanillymandelic acid (VMA) with 4-aminoantipyrine (4-AAP) are prepared and characterized. Different physico-chemical techniques namely IR, magnetic and UV-vis spectra are used to investigate the structure of these chelates. Cu(II) forms 1:1 (Cu:DO) and 1:2 (Cu:VMA) chelates. DO behave as a uninegative tridentate ligand in binding to the Cu(II) ion while VMA behaves as a uninegative bidentate ligand. IR spectra show that the DO is coordinated to the Cu(II) ion in a tridentate manner with ONO donor sites of the phenolic- OH, -NH and carbonyl- O, while VMA is coordinated with OO donor sites of the phenolic- OH and -NH. Magnetic moment measurements reveal the presence of Cu(II) chelates in octahedral and square planar geometries with DO and VMA, respectively. The thermal decomposition of Cu(II) complexes is studied using thermogravimetric (TG) and differential thermal analysis (DTA) techniques. The activation thermodynamic parameters, such as, energy of activation, enthalpy, entropy and free energy change of the complexes are evaluated and the relative thermal stability of the complexes are discussed.

  7. Efecto de una sola dosis de ácido zoledrónico en un caso de enfermedad de Paget ósea Effect of a single dose of zoledronic acid in a case of Paget bone disease

    Directory of Open Access Journals (Sweden)

    Melina Sabán

    2010-10-01

    . We administered intravenous zoledronic acid (4 mg in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget´s disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.

  8. Glucosamine hydrochloride

    Science.gov (United States)

    ... combination of glucosamine hydrochloride, chondroitin sulfate, and manganese ascorbate. Some evidence suggests that this combination can improve ... combination of glucosamine hydrochloride, chondroitin sulfate, and calcium ascorbate twice daily reduces joint swelling and pain, as ...

  9. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Science.gov (United States)

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  10. 唑来膦酸盐治疗重度绝经后骨质疏松及腰背痛的临床观察%Clinical Efficacy of Zoledronic Acid on Osteoporosis and Back Pain of Postmenopausal Women

    Institute of Scientific and Technical Information of China (English)

    于斌; 夏英鹏; 杜文军; 李辉南; 高军伟

    2015-01-01

    Objective To evaluate the clinical efficacy of 5mg of zoledronic acid in the treatment of osteoporosis and back pain of postmenopausal women.Methods Randomized comparative study was taken.From April 2012 to April 2013, a total of 84 patients with osteoporosis and back pain were randomly divided into experimental group and control group, with 42 cases in each group.All the patients were continually treated with 600mg of calcium, Vitamin D 124 IU/d and calcitriol 0.25 μg/d for one year.Patients of ex-perimental group received 5mg zoledronic acid once.The lumbar spine (LS) and total hip (TP) bone mineral density (BMD), blood calcium, X-ray examination of thoracolumbar spine, VAS pain sore and ODI were carried out before treatment and after treatment for 12 months.Results 39 patients in experimental group and 40 patients in control group were followed up for more than 12 months.In experimental group, BMD of LS increased by 5.8%, TP by 3.5%, with significant difference.In control group, BMD of LS and TP increased by 2.0% and 1.4% with significant difference.The increases of MBD (both LS and TP) of experimental group were greater than those in control group, and the difference was statistically significant.After 12 months, VAS scores, ODI scores, the increase of VAS and ODI in experimental group were greater than those in control group, and the difference was statistically significant.There were no new clinical vertebral fractures in both groups and no serious adverse reactions in experimental group.Conclusion A once-yearly use of zoledronic acid (5 mg) can significantly increase the BMD of lumbar spine and hip, and released back pain prominently. With the good compliance and tolerance of patients, zoledronic acid (5 mg) is an important means of treating osteoporosis.%目的:分析应用唑来膦酸盐5 mg 治疗重度绝经后骨质疏松及腰背痛的临床疗效。方法采用随机对照研究,选取2012年4月至2013年4月以腰背痛就诊的

  11. Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

    Science.gov (United States)

    Charehbili, A; van de Ven, S; Smit, V T H B M; Meershoek-Klein Kranenbarg, E; Hamdy, N A T; Putter, H; Heijns, J B; van Warmerdam, L J C; Kessels, L; Dercksen, M; Pepels, M J; Maartense, E; van Laarhoven, H W M; Vriens, B; Wasser, M N; van Leeuwen-Stok, A E; Liefers, G J; van de Velde, C J H; Nortier, J W R; Kroep, J R

    2014-05-01

    The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

  12. Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

    Science.gov (United States)

    Zysk, Aneta; DeNichilo, Mark O; Panagopoulos, Vasilios; Zinonos, Irene; Liapis, Vasilios; Hay, Shelley; Ingman, Wendy; Ponomarev, Vladimir; Atkins, Gerald; Findlay, David; Zannettino, Andrew; Evdokiou, Andreas

    2017-02-01

    Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases. Copyright © 2016. Published by Elsevier Ireland Ltd.

  13. 唑来膦酸联合化疗治疗恶性肿瘤骨转移32例临床分析%Clinical efficacy of zoledronic acid combined with chemotherapy in the treatment of malignant tumor with bone metastases

    Institute of Scientific and Technical Information of China (English)

    李学超

    2014-01-01

    目的:观察唑来膦酸联合化疗对恶性肿瘤骨转移的临床疗效及不良反应。方法:将64例恶性肿瘤骨转移患者随机分为2组,其中对照组32例单用化疗;治疗组32例接受唑来膦酸联合化疗,2组化疗方案相同。结果:治疗组疼痛总有效率81.3%,对照组为46.9%。治疗组骨病灶控制总有效率62.5%,对照组为28.1%;治疗组均优于对照组(P<0.01)。2组无严重不良反应发生。结论:唑来膦酸联合化疗治疗恶性肿瘤骨转移疗效确切,优于单用化疗,且不良反应少,患者依从性好。%Objective:To investigate the effects and adverse reactions of zoledronic acid combined with chemotherapy in the treatment of malignant tumor with bone metastases. Methods:Sixty-four malignant tumor patients with bone metastases were randomly divided into the control group and trial group(32 cases each group). The control group and trial group were treated with single chemotherapy and zoledronic acid combined with chemotherapy,respectively. The chemotherapy regimens of two groups were the same. Results:The totally effective rates of curing pain in trial group and control group were 81. 3% and 46. 9%, respectively. The totally effective rates of controlling bone metastases in trial group and control group were 62. 5% and 28. 1%,respectively. The treatment effect in trial group was better than that in control group(P<0. 01),no serious adverse reaction in two groups was found. Conclusions:The therapeutic effect of zoledronic acid combined with chemotherapy is better than that of single chemotherapy. The adverse reaction of zoledronic acid combined with chemotherapy is slight,and the patient is well-tolerated.

  14. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    Science.gov (United States)

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  15. Clinical study on zoledronic acid combined with calcium carbonate D3 in treatment of osteoporosis%唑来膦酸联合碳酸钙D3治疗骨质疏松症的临床研究

    Institute of Scientific and Technical Information of China (English)

    郭丙杰; 张东洋; 李少华

    2015-01-01

    Objective To evaluate the clinical efficacy of zoledronic acid combined with calcium carbonate D3 in treatment of osteoporosis. Methods The patients with osteoporosis (120 cases) of Ninth People’s Hospital of Zhengzhou City from January 2010 to September 2013 were randomly divided into control and treatment groups, and each group had 60 cases. The patients in the control group were po administered with Calcium Carbonate D3 Tablets, 1 tablet/time, twice daily. The patients in the control group were iv administered with Zoledronic Acid Injection (5 mg diluted with 100 mL physiological saline) more than 15 min, 1 time/year. The patients in two groups were treated for one year. After the treatment, the efficacy was evaluated, and the changes of BMD, VAS score, blood calcium, phosphorus and AKP were compared in two groups. Results The efficacies in the control and treatment groups were 65.0% and 96.7%, respectively, and there were differences between two groups (P< 0.05). After treatment, BMD of L1 - 4 and blood calcium in treatment group were significantly elevated, while the AKP and VAS score was significantly reduced, and the differences were statistically significant in the same group (P < 0.05, 0.01). Degree of the improvement in the treatment group was better than that in the control group, with significant difference between two groups (P<0.05). Conclusion Zoledronic acid combined with calcium carbonate D3 has the good clinical effect in treatment of osteoporosis, and can relieve patients’ pain, while can improve and maintain the BMD level with high safety, which is worth clinical promotion.%目的:探讨唑来膦酸联合碳酸钙D3治疗骨质疏松症的临床疗效。方法2010年1月-2013年9月郑州市第九人民医院收治的骨质疏松症患者120例,随机分为对照组和治疗组,每组60例。对照组口服碳酸钙D3片,1片/次,2次/d。治疗组在对照组基础上静脉滴注唑来膦酸注射液(5 mg以100 mL生理盐水

  16. 唑来膦酸联合钙尔奇D治疗原发性骨质疏松症的研究%Clinical study of Zoledronic acid injection combined with Caltrate D on treatment for primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    刘国强; 姜世平; 徐谦

    2012-01-01

    目的 探讨唑来膦酸联合钙尔奇D治疗原发性骨质疏松症患者的临床疗效.方法 选择2010年10月-2011年12月收治的原发性骨质疏松症患者31例,分为研究组16例,年龄(67±4.8)岁,对照组15例,年龄(66.4±4.3)岁.所有患者均初次诊断为骨质疏松症,且未进行系统抗骨质疏松症治疗,排除患有骨代谢性疾病或服用影响骨代谢药物情况.两组患者均给予钙尔奇D片口服,600 mg 1次/d;研究组患者则于治疗初期滴注唑来膦酸注射液5mg1次/d.比较两组患者治疗后药物不良反应、随访6个月后骨密度(BMD)改善程度、疼痛缓解程度、有否合并骨折等情况.结果 研究组患者BMD平均增长率为10.67%,且较对照组增长明显,疼痛及活动改善优良率为75%,无骨坏死、新发骨折.用药后不良反应:恶心54%、低热38%、全身骨关节疼痛加重23%、无症状低钙血症16%,且上述症状均于药物输注3d后明显缓解,随访未见反复;对照组患者BMD平均增长率为2.48%,疼痛及活动改善优良率为26.7%,新发骨折2例,未见药物不良反应,两组比较,研究组优于对照组,差异有统计学意义(P<0.05).结论 唑来膦酸注射液联合钙尔奇D口服是治疗原发性骨质疏松症患者安全有效的方法.%Objective To observe the clinical effect of Zoledronic acid injection combined with Caltrate D on treatment for primary osteoporosis. Methods Choose 31 cases of primary osteoporosis patients since October 2010 to December 2011, who were diagnosed for the first time without any systemic treatment. 31 patients were divided into two groups, there were 16 cases in the research group, aged (67 ?.8) years and 15 cases in the control group, aged (66.4 ?.3) years. Two groups were equally given Caltrate 600mg once a day, while the research group received the treatment of the Zoledronic acid injection 5mg early. After that, we compared the different situations such as adverse drug

  17. A contribution to the determination of aflatoxin B1, quinine hydrochloride and L(+)-ascorbic acid in foodstuffs by quantitative in situ thin-layer chromatographic analysis

    NARCIS (Netherlands)

    Beljaars, P.R.

    1974-01-01

    The application of quantitative thin-layer chromatography (TLC) involving in situ spectrodensitometric measurements with a flying-spot densitometer is described in this study for the analysis of aflatoxin B 1 , quinine hydrochloride and L(+)-ascorbic acid (vitamin C

  18. Infrared and Raman spectroscopy and DFT calculations of DL amino acids: Valine and lysine hydrochloride

    Science.gov (United States)

    Paiva, F. M.; Batista, J. C.; Rêgo, F. S. C.; Lima, J. A.; Freire, P. T. C.; Melo, F. E. A.; Mendes Filho, J.; de Menezes, A. S.; Nogueira, C. E. S.

    2017-01-01

    Single crystals of DL-valine and DL-lysine hydrochloride were grown by slow evaporation method and the crystallographic structure were confirmed by X-ray diffraction experiment and Rietveld method. These two crystals have been studied by Raman spectroscopy in the 25-3600 cm-1 spectral range and by infrared spectroscopy through the interval 375-4000 cm-1 at room temperature. Experimental and theoretical vibrational spectra were compared and a complete analysis of the modes was done in terms of the Potential Energy Distribution (PED).

  19. Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid.

    Science.gov (United States)

    Kohinata, Takeru; Fujii, Mitsuo; Nakamura, Souichiro; Hamada, Noritaka; Yonemochi, Etsuo; Terada, Katsuhide

    2004-12-01

    We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.

  20. 唑来膦酸、降钙素对骨生化标志物BAP、N-MID、β-CTX的影响%Effect of zoledronic acid and calcitonin on bone metabolic biochemical markers, BAP, N-MID, and β-CTX

    Institute of Scientific and Technical Information of China (English)

    孔西建; 吴丹; 叶进; 廉杰

    2013-01-01

    目的 通过监测绝经后骨质疏松症患者使用唑来膦酸、降钙素治疗前后骨代谢生化标志物的变化来分析二者对骨代谢的影响.方法 回顾性分析绝经后骨质疏松症病例115例,55例使用唑来膦酸(5mg静滴一次),60例使用鲑鱼降钙素(50IU隔日一次肌注,治疗90日),检测每个病例治疗前和开始治疗后4周、8周、12周的BAP、N-MID、β-CTX,并进行统计学分析.结果 降钙素组治疗4周后BAP、β-CTX与治疗前相比降低(P<0.05),骨转换率降低;治疗8周、12周后β-CTX仍明显降低(P<0.05),但BAP与治疗前相比变化无统计学意义;唑来膦酸组治疗4周、8周后BAP、N-MID、β-CTX与治疗前相比均明显降低(P<0.05),骨转换率明显降低;治疗后12周后BAP、β-CTX仍明显降低(P<0.05);与降钙素组相比,唑来膦酸组治疗后4周、8周BAP、N-MID、β-CTX降低更明显(P<0.05),骨转换率降低更明显;治疗后12周BAP、β-CTX仍明显降低(P<0.05).两种药物均具有较好的安全性.结论 降钙素组、唑来膦酸组均可有效抑制骨吸收,降低骨转换率;与降钙素相比,唑来膦酸抑制骨吸收的作用更迅速、更稳定,病人低骨转换持续时间更久.%Objective To analyze the effect of zoledronic acid or calcitonin on bone metabolism by monitoring the changes of bone metabolic markers before and after the treatment of zoledronic acid or calcitonin in patients with postmenopausal osteoporosis. Methods The data of 115 patients with postmenopausal osteoporosis was analyzed retrospectively. Fifty-five patients were treated with zoledronic acid ( 5mg intravenous drip once ). Sixty patients were treated with salmon calcitonin ( 50U intramuscular injection every other day, lasting for 90 days ). BAP, N-MID , and β-CTX was tested before and 4-, 8-, and 12-week after the treatment. All the results were analyzed statistically. Result BAP and β-CTX in patients in calcitonin treatment group after 4-week treatment were

  1. Comparison of hot hydroxylamine hydrochloride and oxalic acid leaching of stream sediment and coated rock samples as anomaly enhancement techniques

    Science.gov (United States)

    Filipek, L.H.; Chao, T.T.; Theobald, P.K.

    1982-01-01

    A hot hydroxylamine hydrochloride (H-Hxl) extraction in 25% acetic acid is compared with the commonly used oxalic acid extraction as a method of anomaly enhancement for Cu and Zn in samples from two very different metal deposits and climatic environments. Results obtained on minus-80-mesh stream sediments from an area near the Magruder massive sulfide deposit in Lincoln County, Georgia, where the climate is humid subtropical, indicate that H-Hxl enhances the anomaly for Cu by a factor of 2 and for Zn by a factor of 1.5, compared to the oxalic method. Analyses of Fe oxide-coated rock samples from outcrops overlying the North Silver Bell porphyry copper deposit near Tucson, Arizona, where the climate is semi-arid to arid, indicate that both techniques effectively outline the zones of hydrothermal alteration. The H-Hxl extraction can also perform well in high-carbonate or high-clay environments, where other workers have suggested that oxalic acid is not very effective. Therefore, the H-Hxl method is recommended for general exploration use. ?? 1982.

  2. Analysis on the curative effect of combination therapy with zoledronic acid and 89SrCL2 on bone tumor with breast cancer metastasis%89SrCL2与唑来膦酸联合治疗乳腺癌转移性骨肿瘤的疗效分析

    Institute of Scientific and Technical Information of China (English)

    刘超; 邓智勇; 刘鹏杰; 贾莉

    2014-01-01

    Objective To discuss the clinical effects of radionuclide 89SrCl2 combined zoledronic acid treatment for hormone dependent breast neoplasm metastatic osteoma. Methods Clinical data of 64 patients with hormone dependent breast neoplasm metastatic osteoma were analyzed retrospectively. All of these patients were divided into 3 groups:one group of 22 cases treated with 89SrCl2(89SrCl2 group);another group of 21 cases treated with zoledronic acid(zoledronic acid group);and the last group of 21 cases treat-ed with 89SrCl2 and zoledronic acid(combination group). Then patients′metastatic lesion curative effects, the condition of bone pain remission, quality of life and bone marrow inhibitory reaction after treatment were observed. Results The effective rate, visual analogue scale decline rate, whole body KPS score in-crease rate and bone marrow inhibitory reaction rate of the 89SrCl2 group were 36.4%(8/22), 77.3%(17/22), 63.6%(14/22), 27.2%(6/22), and which were 33.3%(7/21), 71.4%(15/21), 52.4%(11/21), 19.0%(4/21) and 42.9%(9/21), 90.5%(19/21), 90.5%(19/21), 33.3%(7/21) in zoledronic acid group and combination group respectively. Conclusion 89SrCl2 combined with zoledronic acid on treating hormone dependent breast neoplasm metastatic osteoma has significant curative effect, and can relieve pain with less adverse reactions, and the combined treatment effects are better than that of 89SrCl2 or zoledronic acid alone.%目的:探讨放射性核素二氯化锶(89SrCl2)联合唑来膦酸治疗激素依赖型乳腺癌转移性骨肿瘤的临床疗效。方法回顾性分析64例激素依赖型乳腺癌转移性骨肿瘤患者的临床资料,将所有患者分为3组:89SrCl2治疗组22例;唑来膦酸治疗组21例;89SrCl2联合唑来膦酸治疗组21例;观察治疗后转移病灶疗效、骨痛缓解情况、生活质量状况、骨髓抑制反应情况。结果89SrCl2治疗骨转移病灶有效率为36.4%(8/22),视觉模拟评分下降率为77.3%(17

  3. Selective and Efficient Oxidation of Aldehydes to Their Corresponding Carboxylic Acids Using H2O2/HC1 in the Presence of Hydroxylamine Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    BAHRAMI,Kiumars; KHODAEI,Mohammad Mehdi; KAMALI,Shahab

    2008-01-01

    A wide variety of aldehydes were efficiently converted to their corresponding carboxylic acids in high yields using H2O2/HC1 in the presence of hydroxylamine hydrochloride.In addition,selective oxidation of aldehydes in the presence of other functional groups such as hydroxyl group,carbon-carbon double bond and other heteroatoms can be considered a noteworthy advantage of this method.

  4. Observation and nursing of the transient adverse effect of zoledronic acid in the treatment of postmenopausal osteoporosis%唑来膦酸治疗绝经后骨质疏松症的一过性反应的观察与护理

    Institute of Scientific and Technical Information of China (English)

    庞雪; 刘英; 曹积弘; 王莉; 郭岩; 王立恒

    2013-01-01

    目的:观察唑来膦酸治疗绝经后骨质疏松症的一过性药物反应并探讨护理措施。方法22例患者均为绝经后骨质疏松症患者。均给予唑来膦酸5 mg/100 ml静脉滴注15 min以上输完。给药结束后记录治疗效果及不良反应。所有患者给予心理护理,用药护理及治疗后不良反应的处理。结果唑来膦酸静脉滴注后主要的一过性不良反应为发热(>37.5℃),本科用药患者均出现发热(22例),其次症状为肌痛16例,流感样症状15例,关节痛10例,头痛5例。以上症状均为一过性,不超过48小时,并且给予非甾体类抗炎镇痛类药物后症状可缓解。2例第二次用药患者均未出现任何不良反应。血细胞分析及肝肾功检查均未出现异常。结论唑来膦酸给药后会出现发热、肌痛等反应,但均为一过性,通过采用积极的用药后护理措施可以提高用药的安全性避免药物反应带来的不良影响。%Objective To observe the transient drug reaction of zoledronic acid in the treatment of postmenopausal osteoporosis , and to explore the nursing intervention method .Methods In this study, 22 patients were diagnosed with postmenopausal osteoporosis .All the patients were treated with an intravenous drip of 5mg/100ml zoledronic acid for more than 15 minutes.Therapeutic effect and adverse reaction were recorded after the administration .All patients received psychological care , medication care , and treatment of adverse reaction after the administration .Results The main adverse reaction was fever ( >37.5℃) after the intravenous drip of zoledronic acid .All the 22 patients in our department had fever .The other symptoms were myalgia ( 16 cases ) , influenza-like symptoms (15 cases), joint pain (10 cases), and headache (5 cases).All these symptoms were transient, lasting less than 48 hours, and relieved after treated with non-steroidal anti-inflammatory drugs.Two patients had no

  5. Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer hydrochloride in hemodialysis patients

    National Research Council Canada - National Science Library

    Ahmadi, Farrokhlagha; Shamekhi, Fatemeh; Lessan-Pezeshki, Mahbob; Khatami, Mohammad Reza

    2012-01-01

    ...), and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available...

  6. pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

  7. Zoledronate and Ion-releasing Resins Impair Dentin Collagen Degradation

    Science.gov (United States)

    Tezvergil-Mutluay, A.; Seseogullari-Dirihan, R.; Feitosa, V.P.; Tay, F.R.; Watson, T.F.; Pashley, D.H.; Sauro, S.

    2014-01-01

    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers. PMID:25074494

  8. Determination of ranitidine hydrochloride in pharmaceutical preparations by titrimetry and visible spectrophotometry using bromate and acid dyes.

    Science.gov (United States)

    Basavaiah, K; Nagegowda, P

    2004-02-01

    Four new methods using titrimetry and spectrophotometry are described for the determination of ranitidine hydrochloride (RNH) with potassium bromate as the oxidimetric reagent and acid dyes, methyl orange, indigo carmine and metanil yellow. In direct titrimetry (method A), the drug is titrated directly with bromate in acid medium and in the presence of excess of bromide using methyl orange indicator. In back titrimetry (method B), the drug is treated with a measured excess of bromate in the presence of bromide and acid, and the unreacted bromine is determined iodometrically. Both spectrophotometric methods are based on the oxidation of RNH by a known excess of bromate in acid medium and in the presence of excess of bromide followed by estimation of surplus oxidant by reacting with either indigo carmine (method C) or metanil yellow (method D), and measuring the absorbance at 610 or 530 nm. In methods B, C and D, reacted oxidant corresponds to the drug content. The experimental conditions are optimized. Titrimetric procedures are applicable over the ranges 1-10 mg (A) and 1-17 mg (B), and the reaction stoichiometry is found to be 1:1 (BrO(-)(3): RNH). In spectrophotometric methods, the absorbance is found to increase linearly with increasing concentration of RNH, which is corroborated by the calculated correlation coefficient (r) of 0.9984 (C) and 0.9976 (D). The systems obey Beer's law for 2-12 and 1-7 microg ml(-1), for methods C and D, respectively. Method D with a molar absorptivity of 9.82 x 10(4) l mol(-l) cm(-1) is found to be more sensitive than method C ( epsilon = 2.06 x l0(4) l mol(-1) cm(-1)). The limits of detection and quantification are reported for both the spectrophotometric methods. The proposed methods were applied successfully to the determination of RNH in tablets and injections. The reliability of the assay was established by parallel determination by the official method and by recovery studies.

  9. Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer hydrochloride in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Farrokhlagha Ahmadi

    2012-01-01

    Full Text Available Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis (HD, and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available. In this study, 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two week washout period without phosphate binders, the patients were randomly divided into two equal groups (n = 20 and were started on nicotinic acid or sevelamer for a period of four weeks. The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of the total calcium (Ca, phosphorus (P, alkaline phosphatase (ALP, triglyceride (TG, total cholesterol (Chol, high-density lipoprotein (HDL, low-density lipoprotein (LDL, uric acid and parathyroid hormone (PTH. Patients receiving sevelamer showed a significant reduction in serum P level (2.2 ± 0.69 mg/dL; P <0.0001 in comparison with the nicotinic acid group (1.7 ± 1.06 mg/dL; P = 0.004. Reduction in the Ca-P product was significantly different in the two groups; in the sevelamer group, it was 21 ± 7; (P <0.0001 while in the nicotinic acid group, it was 16 ± 11 (P = 0.007. Also, patients on sevelamer showed greater reduction in the mean TG level (38.9 ± 92 mg/dL; P = 0.005. No significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP and iPTH levels in the two study groups. Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product.

  10. β-氨基酸乙酯盐酸盐的合成与表征%Synthesis and Characterization of β-Amino Acid Ethyl Ester Hydrochlorides

    Institute of Scientific and Technical Information of China (English)

    韩秋敏; 李登超

    2011-01-01

    β-Phenylalanine ethyl ester hydrochloride,2-F-β-phenylalanine ethyl ester hydrochloride and 3-F-β-phenylalanine ethyl ester hydrochloride were synthesized by reacting amino acids with ethanol in the presence of thionyl chloride,respectively.The structures of these compounds were characterized by melting point,1H-NMR,13C-NMR and mass spectrometry.This synthetic method was simple,with mild reaction conditions and the yields above 85%.%以三种β-苯丙氨酸、二氯亚砜、乙醇为原料分别合成了β-苯丙氨酸乙酯盐酸盐、2F-β-苯丙氨酸乙酯盐酸盐和3F-β-苯丙氨酸乙酯盐酸盐三种稳定的β-氨基酸乙酯盐酸盐,并通过熔点、核磁和质谱对化合物的结构进行了表征。该合成方法操作简单、反应条件温和,收率均在85%以上。

  11. Erlotinib hydrochloride.

    Science.gov (United States)

    Minna, John D; Dowell, Jonathan

    2005-05-01

    Erlotinib hydrochloride (Tarceva; OSI Pharmaceuticals/Genentech/Roche), a member of a class of targeted anticancer drugs that inhibit the activity of the epidermal growth factor receptor, was approved by the US FDA in November 2004 for the treatment of advanced non-small-cell lung cancer after failure of at least one prior chemotherapy regimen. It is the first such drug to demonstrate an increase in survival in Phase III trials in patients with advanced non-small-cell lung cancer.

  12. Comparison of the efficacy of ethylenediaminetetraacetic acid and tetracycline hydrochloride as root conditioning agents: An in vitro study

    Directory of Open Access Journals (Sweden)

    Tarun Nanda

    2012-01-01

    Full Text Available Objective: Root surfaces of periodontitis-affected teeth are hypermineralized and contaminated with cytotoxic and other biologically active substances. Various root conditioning agents have been recommended as an adjunct to mechanical root surface debridement to expose dentin collagen and cementum bound proteins. The aim of the present in vitro study was to compare the efficacy of ethylenediaminetetraacetic acid (EDTA and tetracycline hydrochloride (HCl as root conditioning agents on planed root surfaces. Materials and Methods: A total of 20 human maxillary anterior teeth indicated for extraction due to chronic periodontitis were collected and root planed. The teeth were sectioned and specimens were divided into two groups - Group I and II. Group I dentin specimens were treated with EDTA and Group II specimens were treated with tetracycline HCl solution at a concentration of 10% by active burnishing technique for 3 min. The root surface samples were then examined by scanning electron microscope. Results: The results of this study showed that EDTA and tetracycline HCl were equally effective in removing the smear layer. It was observed that the total and patent dentinal tubules were more in number in teeth treated with tetracycline when compared to EDTA group. However, EDTA was found to be much more effective as root conditioning agent because it enlarged the diameter of dentinal tubules more than that of tetracycline HCl. Conclusion: The results of in vitro study showed that both the agents are good root conditioning agents if applied in addition to periodontal therapy. However, further studies are required to establish the in vivo importance of EDTA and tetracycline HCL as root conditioners.

  13. Removal of Chloroform from Hydrochloride Acid Solution Using Fine Powder of Polymer as Adsorbent

    Institute of Scientific and Technical Information of China (English)

    LU,Yingzhou; QUE,Yong; LI,Chunxi; MENG,Hong; WANG,Zihao

    2009-01-01

    In order to choose a suitable adsorbent for the removal of chloroform from its hydrochloric acid solution,the adsorptive ability of some polymer adsorbents was investigated in terms of their adsorption curves in water and 20% hydrochloric acid solutions at 298.15 K,and compared with that of active carbon (AC) and solid paraffin (SP).The adsorbents studied include the fine powders of chlorinated rubber (CR),polypropylene (PP),chlorinated polypropylene (CPP) and polyvinylchloride (PVC).The results showed that the adsorption behavior followed the Langmuir equation and the adsorption ability of these adsorbents followed the order AC > PVC > CR > PP > CPP> SP.This order is basically in line with the decrease of chloro-content of the adsorbents from PVC to SP.The adsorptivity of PVC and CR was nearly equivalent to that of AC with their saturated adsorption being about 1.4 g-CHCl3 (g-absorbent) -1.For all adsorbents studied,the adsorption capacity always decreases with the increase of hydrochloric acid concentration.It is showed that the commercial polymer powder of PVC or CR can be used as an efficient absorbent for the removal of chloroform from its aqueous solution for its low cost,good adsorption ability and ease of thermal desorption for recycling.

  14. Effects of Zoledronate on Mortality and Morbidity after Surgical Treatment of Hip Fractures

    Science.gov (United States)

    Cengiz, Ömer; Polat, Gökhan; Karademir, Gökhan; Tunç, Oytun Derya; Erdil, Mehmet; Tuncay, İbrahim; Şen, Cengiz

    2016-01-01

    We aimed to evaluate the effects of intertrochanteric femoral fractures on mortality, morbidity, and cost of zoledronate treatment in elderly patients treated by osteosynthesis. Based on Evans classification, 114 patients with unstable intertrochanteric femoral fractures were treated with osteosynthesis. After the surgical treatment of intertrochanteric fractures, the treatment group (M/F, 24/32; mean age, 76.7 ± SD years) received zoledronate infusion, and the control group (M/F, 20/38; mean age, 80.2 ± SD years) received placebo. Postoperative control visits were performed at 6-week, 3-month, 6-month, and 12-month time points. Functional level of patients was evaluated by the modified Harris hip score and Merle d'Aubigné hip score. By 12 months, the mean HHS in treatment and control groups was 81.93 and 72.9, respectively. For time of death of the patients, mortality was found to be 57.1% (16/28) on the first 3 months and 92.9% (26/28) on the first six months. The mortality rate in the treatment and control groups was 14.3% (8/56) and 34.5% (20/58), respectively. The use of zoledronic acid after surgical treatment of intertrochanteric femoral fractures in osteoporotic elderly patients is a safe treatment modality which helps to reduce mortality, improves functional outcomes, and has less side effects with single dose use per year. PMID:27092280

  15. 1型糖尿病模型大鼠股骨骨代谢紊乱及唑来膦酸的影响%Effects of zoledronic acid on bone metabolism disturbance in the femur of type 1 diabetic rat models

    Institute of Scientific and Technical Information of China (English)

    曹鲁宁; 崔敏; 于灵芝; 张娜; 赵旭

    2015-01-01

    BACKGROUND:Osteoporosis caused by diabetes melitus as common secondary osteoporosis has been paid more and more attention recently. Zoledronic acid serves as a novel drug for osteoporosis, and its effect on osteoblasts in vivo remains unclear. OBJECTIVE:To investigate the changes of the expression of bone morphogenetic protein 2 andNoggin in the femur of type 1 diabetes melitus rats and the effect of zoledronic acid on them. METHODS:Models of type 1 diabetes melitus were established by intraperitoneal injection of streptozotocin in 130 Wistar rats. 3 days later, rats with blood sugar > 16.7 mmol/L for three consecutive times were considered as successful models, 120 in total. These models were randomly divided into model, prevention and treatment groups. Rats in the prevention and treatment groups were intravenously administered zoledronic acid (0.1 mg/kg) on the day of modeling and 2 weeks after model establishment. An additional 40 rats were injected with citrate buffer solution as control group. RESULTS AND CONCLUSION: Compared with the control group, femur bone mineral density, serum alkaline phosphatase levels, and femur bone morphogenetic protein 2 mRNA expression levels were significantly lower in the model group (P 16.7 mmol/L鼠为造模成功鼠,共120只,随机等分为模型组、预防组和治疗组。后2组大鼠分别在造模后当天和2周后一次性静脉给予唑来膦酸(0.1 mg/kg)。另取40只大鼠注射柠檬酸缓冲液作为对照组。结果与结论:与对照组相比,模型组大鼠股骨骨密度、血清碱性磷酸酶水平、股骨骨形态发生蛋白2 mRNA表达水平明显降低(P <0.05),Noggin mRNA表达水平显著升高(P <0.05)。与模型组相比,预防组和治疗组大鼠骨密度和骨形态发生蛋白2 mRNA表达水平显著升高(P <0.05),Noggin mRNA表达水平显著降低(P <0.05),血清骨碱性磷酸酶水平也逐渐恢复。提示1型糖尿病大鼠骨代谢紊乱在病程早期即出现,

  16. 唑来膦酸局部治疗对骨质疏松时自体髂骨移植内种植体骨结合的影响%Effect of Local Treatment with Zoledronate Acid on Osseointegration of Dental Implants in Autologous lllac Graft in Os teoporotic Rabbits.

    Institute of Scientific and Technical Information of China (English)

    李剑平; 戚孟春; 石燕萍; 于静; 胡静

    2011-01-01

    Objective: To investigate the effect of local treatment with zoledronate acid on osseointegration of dental implants in autologous lilac graft in osteoporotic rabbits. Methods: Thirty female rabbits were randomly divided into three groups: A, B and C. Animals in group B and C received bilatreal ovariectomy and group A underwent sham operation. 12 weeks after surgery, femoral bones of rabbits were examined for bone mineral density to verify osteoporosis status. Then bone defects were made at the proximal metaphyses of tibiae and autologous iliac bone graft with simultaneous placement of HA coated titanium implants (group A and B) or zoledronate acid immobilized HA -implants (group C) were performed. Animals were killed at 2 and 12 weeks after bone graft surgery and undecalcified sections were prepared and examined histologically and histomorphometrically. Results: Osteoporotic status was verified in ovariectomized rabbits by significantly decreased BMD when compared to sham-operated animals.At 2 weeks after implantation surgery, thickness of cortical bone, bone volume in cancellous area and implant-bone contact rate in group B and C were similar, but all were significantly lower than those in group A. At 12weeks,TCB, IBCR and BVC were highest in group A, followed by group C, and lowest in group B. Compared with 2 weeks, no significant changes for TCB were found at 12 weeks both in group A and in group C, while TCB in group B was slightly decreased. IBCR and BVC at 12 weeks were significantly increased in all groups when compared with those at 2 weeks, except BVC in group B, which was significantly decreased. Conclusion: Experimental osteoporosis can accelerate resorption of bone grafts and decrease cancellous bone volume and implant-bone contact rate, while local treatment with zoledronate acid may resist the negative influence of osteoporosis and increase osseointagration of dental implants.%目的:研究唑来膦酸局部治疗对骨质疏松时自体髂骨移植

  17. The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus Efeito do ácido zoledrônico nas múltiplas fraturas vertebrais induzidas por glicocorticóide no lúpus eritematoso juvenil

    Directory of Open Access Journals (Sweden)

    Sonia Cristina de Magalhães Souza

    2004-01-01

    Full Text Available Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.Glicocorticóides são fármacos comumente usados no tratamento de pacientes lúpicos, porém apresentam efeitos adversos importantes, principalmente a osteoporose e fraturas. O tratamento da osteoporose em pacientes jovens deve ser eficaz e não prejudicial ao crescimento e remodelamento ósseo. Os bisfosfonatos são drogas que reduzem a incidência de fraturas, mas seu uso em crianças e adolescentes ainda é controverso, devido a seus possíveis efeitos adversos no esqueleto em crescimento. Estudos recentemente publicados demonstraram que o crescimento linear se manteve normal com o uso de bisfosfonatos, não havendo supressão excessiva do remodelamento ósseo ou defeitos de mineralização. O ácido zoledrônico é um novo bisfosfonato endovenoso aprovado pelo FDA para o uso na hipercalcemia das neoplasias e parece ser um tratamento eficaz para a osteoporose p

  18. Acute delirium in an elderly woman following zoledronate administration

    Directory of Open Access Journals (Sweden)

    Mohammad Nasiruddin

    2014-01-01

    Full Text Available Zoledronate is a third-generation bisphosphonate having distinctive profile of high potency as well as prolonged duration of action. Intravenous zoledronate is the recently approved bisphosphonate for the treatment of osteoporosis and has an attractive once-yearly regimen for the treatment of osteoporosis. Here we report, for the first time, a case of acute delirium following zoledronate administration for osteoporosis. An 86-year-old female patient presented to orthopedics out-patient department (OPD with complaints of pain and unable to bear weight on left thigh with history of fall from bed 2 months back. She was diagnosed as fracture neck of femur with severe osteoporosis and treated conservatively. She was given zoledronate IV 5 mg infusion over 30 min. After 10-12 h of zoledronate infusion, patient became confused, disorientated, and agitated. A septic work-up was negative. Electrolyte disturbances were excluded with normal sodium, potassium, calcium, and magnesium levels. Computed tomography of the brain was unremarkable. A metabolic cause could not be found for the change in her mental state. Patient was referred to medicine department where she was diagnosed as drug-induced acute delirium probably due to zoledronate. Patient was advised injections haloperidol and torsemide. In the following 48 h, her confusion got cleared and mental status was improved. According to the Naranjo′s scale, the effect of zoledronate in our patient was scored 6 indicating a probable likelihood of causing delirium. It was a probable cause of acute delirium according to World Health Organization (WHO causality scale.

  19. Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.

    Science.gov (United States)

    Vidal-Gutiérrez, X; Gómez-Clavel, J-F; Gaitán-Cepeda, L-A

    2017-03-01

    Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson's trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models.

  20. pH-sensing properties of cascaded long- and short-period fiber grating with poly acrylic acid/poly allylamine hydrochloride thin-film overlays

    Science.gov (United States)

    Yang, Ying

    2014-11-01

    Based on coupled-mode theory and transfer matrix method, the mode coupling mechanism and the reflection spectral properties of coated cascaded long- and short-period gratings (CLBG) are discussed. The effects of the thin-film parameters (film refractive index and film thickness) on the reflection spectra of the coated CLBG are simulated. By using electrostatic self-assembly method, poly acrylic acid (PAA) and poly allylamine hydrochloride (PAH) multilayer molecular pH-sensitive thin-films are assembled on the surface of the partial corroded CLBG. When the CLBG coated with PAA/PAH films are used to sense pH values, the resonant wavelengths of the CLBG have almost no shift, whereas the resonance peak reflectivities change with pH values. In addition, the sensitivities of the resonance peak reflectivities responding to pH values are improved by an order of magnitude.

  1. Cartap Hydrochloride Poisoning.

    Science.gov (United States)

    Kalyaniwala, Kimmin; Abhilash, Kpp; Victor, Peter John

    2016-08-01

    Cartap hydrochloride is a moderately hazardous nereistoxin insecticide that is increasingly used for deliberate self-harm in India. It can cause neuromuscular weakness resulting in respiratory failure. We report a patient with 4% Cartap hydrochloride poisoning who required mechanical ventilation for 36-hours. He recovered without any neurological deficits. We also review literature on Cartap hydrochloride poisoning.

  2. Dynamic Changes of Ephedrine Hydrochloride, Pseudoephedrine Hydrochloride, Amygdalin and Glycyrrhizic Acid in Different Compatibility of San-Ao Decoction%三拗汤不同配伍煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸动态规律变化

    Institute of Scientific and Technical Information of China (English)

    张金花; 刘陶世; 程建明; 陈冬冬; 钱海峰

    2015-01-01

    目的:研究三拗汤在不同配伍煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸的动态规律变化.方法:采用高效液相色谱法(HPLC)同时测定三拗汤煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸的转移率,选用Kromasil C18(4.6 mm×250 mm,5μm)色谱柱,以流动相甲醇-0.1%磷酸进行梯度洗脱,流速为1 mL·min-1,柱温30℃,进样量10μL.其中盐酸麻黄碱、盐酸伪麻黄碱和苦杏仁苷在208 nm波长下检测,甘草酸铵在250 nm波长下检测.结果:麻黄碱转移率在合煎液中大于分煎液,伪麻黄碱转移率在麻黄与苦杏仁配伍中最高,苦杏仁苷转移率在麻黄与苦杏仁配伍中最高,甘草酸转移率在合煎液中大于分煎液.结论:中药复方在煎煮过程中存在动态规律变化,应根据其变化有针对性提高药物的有效性和稳定性.%This paper was aimed to study the dynamic changes of San-Ao(SA) decoction in different compatibility of ephedrine hydrochloride,pseudoephedrine hydrochloride,amygdalin and glycyrrhizic acid.HPLC was used to simultaneously determinate the transfer rate of SA decoction of ephedrine hydrochloride,pseudoephedrine hydrochloride,amygdalin and glycyrrhizic acid.Kromasil C18 (4.6 mm×250 mm,5μm) column was selected with methanol and 0.1% phosphoric acid as a mobile phase to gradient.The flow rate was 1 mL·min-1.The column temperature was 30℃.The injection volume was 10μL.Ephedrine hydrochloride,pseudoephedrine hydrochloride and amygdalin were detected at the wavelength of 208 nm.The glycyrrhizic acid was detected at the wavelength of 250 nm.The results showed that the transfer rate of ephedrine hydrochloride in decoction was more than that of the single preparation.The transfer rate of pseudoephedrine hydrochloride was the highest in the combination of ephedra and bitter almond.The transfer rate of amygdalin was the highest in the combination of ephedra and bitter almond.The transfer rate of

  3. 补肾健骨胶囊联合唑来膦酸注射液和碳酸钙 D3治疗老年骨质疏松症的临床研究%Clinical study of Bushen Jiangu Capsules combined with Zoledronic Acid Injection and calcium carbonate D3 in treatment of aged osteoporosis

    Institute of Scientific and Technical Information of China (English)

    都海; 肖波; 易泽洪; 杨国齐; 刘光勇; 马俊; 刘建伟; 康兵文; 赵明; 彭德全

    2016-01-01

    目的:探讨补肾健骨胶囊联合唑来膦酸注射液和碳酸钙 D3片治疗老年骨质疏松症的临床疗效。方法选择2012年5月—2015年1月在郫县人民医院骨科接受医治的114例骨质疏松症患者为研究对象,所有患者按照治疗方法的不同分为对照组和治疗组,每组各57例。所有患者均口服碳酸钙 D3片,1片/次,1次/d。在此基础上对照组静脉滴注唑来膦酸注射液,5 mg 加入生理盐水250 mL 中,1次/月,每次滴注不少于15 min。治疗组在对照组基础上口服补肾健骨胶囊,4粒/次,3次/d。两组患者均连续治疗12个月。观察两组患者的临床疗效,比较骨代谢指标以及骨密度(BMD)、骨钙素(BGP)、骨形态发生蛋白(BMP-2)及视觉模拟(VAS)评分。结果治疗后,对照组和治疗组总有效率分别为82.46%、94.74%,两组总有效率比较差异有统计学意义(P<0.05)。治疗后,两组血钙(S-Ca)、血磷(S-P)明显增高,碱性磷酸酶(ALP)显著降低,同组治疗前后差异具有统计学意义(P<0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P<0.05)。治疗后,两组患者 L2-L4 BMD、股骨颈 BMD、BGP、BMP-2均明显增加,VAS 评分明显降低,同组治疗前后差异具有统计学意义(P<0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P<0.05)。对照组、治疗组的不良反应发生率分别为7.02%、8.77%,两组不良反应发生率比较差异无统计学意义。结论补肾健骨胶囊联合唑来膦酸注射液和碳酸钙 D3片治疗老年骨质疏松症具有较好的临床效果,可有效增加患者 BMD,明显改善骨代谢,减少骨量流失,值得临床推广应用。%Objective To investigate the clinical effect of Bushen Jiangu Capsules combined with Zoledronic Acid Injection

  4. A volumetric and viscometric study of 4-aminobutyric acid in aqueous solutions of metformin hydrochloride at 308.15, 313.15 and 318.15 K

    Directory of Open Access Journals (Sweden)

    KRISHA RAJAGOPAL

    2011-01-01

    Full Text Available Density (r and viscosity (h measurements were performed for4-aminobutyric acid in 0.05, 0.10 and 0.15 M aqueous metformin hydrochloride at 308.15, 313.15 and 318.15 K. The measured values of density and viscosity were used to estimate some important parameters, such as the partial molal volume, Vf, the standard partial molal volume, Vf, the standard partial molal volume of transfer, DVf, the hydration number, nH, the second derivative of the infinite dilution of the standard partial molal volume with temperature ¶2Vf/¶T2, the viscosity B-coefficients, variation of B with temperature, dB/dT, the free energy of activation per mole of solvent Dm1* and solute Dm2* of the amino acid in a ternary system. These parameters were interpreted in terms of solute–solute and solute–solvent interactions and structure making/breaking ability of solutes in the given solution.

  5. 鲑鱼降钙素联合唑来膦酸注射液治疗老年原发性骨质疏松症的疗效观察%Efficacy of salmon calcitonin combined with zoledronic acid in treatment of senile primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    沈小明; 黄成龙; 陈刚; 龚遂良

    2016-01-01

    One hundred and twenty patients with senile primary osteoporosis were enrolled in the study from January 2012 to April 2013,including 41 males and 79 females.Patients were randomly assigned to two groups:60 patients in study group were treated with salmon calcitonin combined with zoledronic acid (salmon calcitonin 50 IU i.m,q.d for 7 d,then 100 IU q.i.d for 7 d,followed by zoledronic acid 5 mg i.v gtt/y);60 cases in control group were treated with alendronate (70 mg p.o/wk).Both groups received the same doses of calcium.Visual analogue scale (VAS) scores were assessed before,and 1,6 and 12 months after treatment,12-Item Short-Form Health Survey (SF-12) and bone mineral density (BMD) were assessed before and 12 months after treatment.There were no significant differences in all baseline parameters between two groups (P > 0.05).After 1 month of treatment,the VAS scores of study group was lower than that of the control group (2.1 ± 3.0 vs.4.2 ± 3.1,P < 0.05),however,both groups had similar improvements in VAS scores in 6 and 12 months after the treatment (P >0.05).Compared to those before treatment,physical component summary and mental component summary of SF-12 scores after 1 year of treatment were improved significantly in both groups (P < 0.05).Also,BMD was significantly improved after 1 year of treatment in both groups (P < 0.05).The incidence of side effect in study group was lower than that in control group (16% vs.20%,P <0.05).The results indicate that salmon calcitonin combined with zoledronic acid is an effective,safe,reliable and well tolerated therapy for senile primary osteoporosis.The long-term outcomes remain to be determined.%对2012年1月至2013年4月在我院接受诊治的120例老年原发性骨质疏松症患者(男41例,女性79例),除常规补充钙剂外,60例采用鲑鱼降钙素联合唑来膦酸注射液治疗(观察组),60例采用阿仑膦酸钠治疗(对照组).药物剂量为肌肉注射鲑鱼降钙素50 U/次、1

  6. Synthesis, growth, morphology of the semiorganic nonlinear optical crystal L-glutamic acid hydrochloride and its structural, thermal and SHG characterizations

    Energy Technology Data Exchange (ETDEWEB)

    Dhanasekaran, P.; Srinivasan, K. [Crystal Growth Laboratory, Department of Physics, School of Physical Sciences, Bharathiar University, Coimbatore-641 046, Tamil Nadu (India)

    2012-12-15

    One of the halide derivatives of L-glutamic acid which was identified as a semiorganic nonlinear optical material, L-glutamic acid hydrochloride [HOOC(CH{sub 2}){sub 2}CH(NH{sub 2})COOH.HCl], was grown as bulk single crystal and its significant properties were characterized. The stoichiometric title compound was synthesized and the solubility of its recrystallized form in DD water was determined in the temperature range 30-80 C by gravimetric method. Structural confirmation was carried out by powder X-ray diffraction study through lattice parameter verification. Optical quality smaller dimension single crystals were grown from aqueous solution by self nucleation through slow evaporation of solvent method and a large dimension single crystal was grown by slow cooling method with reversible seed rotation technique. Morphological importances of different growth facets of the as grown crystals were studied through optical goniometry. Unit cell structure of the grown crystal was refined by single crystal X-ray diffraction analysis, functional groups present in the crystal responsible for various modes of vibrations were confirmed by FTIR spectroscopy analysis, thermal stability of the grown crystal was analysed by TG/DTA and DSC and second harmonic generation (SHG) of a fundamental Nd:YAG laser beam by Kurtz technique. Results indicate that the grown crystal is in stoichiometric composition and has significant improvement in its thermal and SHG properties when compared to pure L-glutamic acid polymorphs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Differences Between the Concentrations in Rabbit Body Fluid of Berberine Hydrochloride,Chlorogenic Acid,Baicalin,and Their Minimal Inhibitory Concentrations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tao; HUANG Hui-ling; ZHANG Shuang; LU Ping; HU Ge; SUO Zhan-wei; JIANG Dai-xun; MU Xiang

    2009-01-01

    To explore the relationship between the heat-clearing and detoxicating functions and the bacteriostatic actions of berberine hydrochloride (Ber.H),chlorogenic acid (Chlo.A),and baicalin (Bai),their concentrations in rabbit body fluid were compared with their minimal inhibitory concentrations (MICs).Their concentrations in rabbit blood and tissue fluid were determined by reversed-phase high performance liquid chromatography,and their MICs to Escherichia coli were determined by tube dilution method.The results showed that the peak concentrations of Ber.H,Chlo.A,and Bai in rabbit blood were 3.2,5.03,and 7.63 μg mL-1,and in rabbit tissue fluid were 0.12,0.11,and 0.12 μg mL-1,respectively.Their MICs to E.coli were,respectively,1.0×103,3.75×103,and 6.75×103 μg mL-1,which were far higher than the concentrations in rabbit body fluids.This study indicates that Ber.H,Chlo.A,and Bai have weak bacteriostatic actions and do not reach their effective inhibitory concentrations in rabbit body fluids,and their heat-clearing and detoxicating functions are independent on the bacteriostatic actions.

  8. Cell adhesion properties of patterned poly(acrylic acid)/poly(allylamine hydrochloride) multilayer films created by room-temperature imprinting technique.

    Science.gov (United States)

    Lu, Yingxi; Sun, Junqi; Shen, Jiacong

    2008-08-05

    Patterned poly(acrylic acid) (PAA)/poly(allylamine hydrochloride) (PAH) multilayer films with line structures of different lateral size and vertical height were fabricated by a room-temperature imprinting technique, and their cell adhesion properties were investigated. The nonimprinted PAA/PAH multilayer films are cytophilic toward NIH/3T3 fibroblasts and HeLa cells whether PAA or PAH is the outer most layer. In contrast, the PAA/PAH multilayer films with a 6.5-microm-line/3.5-microm-space pattern structure are cytophobic toward NIH/3T3 fibroblasts and HeLa cells when the height of the lines is 1.29 microm. By either increasing the lateral size of the patters to 69-microm-line/43-mum-space or decreasing the height of the imprinted lines to approximately 107 nm, imprinted PAA/PAH multilayer films become cytophilic. This kind of transition of cell adhesion behavior derives from the change of the physical pattern size of the PAA/PAH multilayer films and is independent of the chemical composition of the films. The easy patterning of layer-by-layer assembled polymeric multilayer films with the room-temperature imprinting technique provides a facile way to tailor the cellular behavior of the layered polymeric films by simply changing the pattern dimensions.

  9. 尿N-乙酰-β-D氨基葡萄糖酶、丙氨酸氨肽酶和α1-微球蛋白检测在唑来膦酸致肾损伤早期诊断作用%Effects of detecting of N-acety-beta-D-glucosaminidase,Alanine aminopeptidase andα1-microglobulin in urine on early diag-nosis of kidney injury induced by zoledronic acid

    Institute of Scientific and Technical Information of China (English)

    刘星; 刘大为; 谢晓冬; 郭占文; 郑振东; 张丽辉; 张娇蕊; 刘永叶

    2016-01-01

    目的 探讨尿N-乙酰-β-D氨基葡萄糖酶(NAG)、丙氨酸氨肽酶(AAP)和α1-微球蛋白(α1-MG)检测在唑来膦酸致肾损伤早期诊断中的作用.方法 选取2012年2月至2014年7月沈阳军区总医院收治的100例应用唑来膦酸治疗的恶性肿瘤骨转移患者为研究对象.其中,男性48例,女性52例,年龄25~82岁,平均(60±11)岁.患者接受唑来膦酸注射液4 mg静脉滴注,1次/25~35 d,30 min滴完,连续应用3次.每次用药前和用药次日,留取患者清晨尿液及静脉血,检测并比较尿NAG、AAP、α1-MG和血肌酐(Scr)、尿素氮(BUN)水平.结果 每次用药前、后比较尿NAG水平,差异均有统计学意义(P0.05);而第2次和第3次用药前后,尿α1-MG水平比较,差异有统计学意义(P0.05).每次用药前后,Scr、BUN水平比较,差异均无统计学意义(P>0.05).3次用药后,尿NAG、α1-MG水平组间比较,差异均有统计学意义(P0.05).结论 唑来膦酸致肾损伤患者尿NAG、AAP和α1-MG水平变化早于血肌酐.尿NAG、AAP和α1-MG联合检测可作为肾损伤的早期诊断指标.%Objective To explore the effects of detecting of N-acety-beta-D-glucosaminidase( NAG) ,Alanine aminopeptidase( AAP) andα1-microglobulin(α1-MG) in urine on early diagnosis of kidney injury induced by zoledronic acid. Methods A total of 100 pa-tients comprised 48 males and 52 females with a mean age of (60 ± 11)years were enrolled into the study. The patients with malignant tumor bone metastasis and received zoledronic acid from February 2012 to July 2014 in the General Hospital of Shenyang Military Command. They received IV infusion of zoledronic acid 4 mg,once for 25 to 35 days,finished within 30 minutes. The therapy was ap-plied 3 times continuously. The patients′urine and venous blood samples were taken before and after each medication′s morning. The level of NAG,AAP and α1-MG in urine and serum creatinine,blood urea nitrogen were detected and compared. Results The differ

  10. 唑来膦酸注射液+钙制剂+ VD 对骨质疏松患者症状缓解情况的对照研究%A case - control study of Zoledronic acid injection + calcium preparations + VD in symptoms miti-gation patients with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    亢鸿儒

    2016-01-01

    目的:探讨骨质疏松患者采用唑来膦酸注射液+钙制剂+维生素 D(VD)对症状缓解的效果。方法选取灵宝市第一人民医院2013年2月至2015年2月收治的骨质疏松患者60例,随机分为钙制剂+ VD 治疗组(对照组)与联用唑来膦酸注射治疗组(观察组),每组30例。比较两组患者的临床效果。结果两组患者治疗前左股骨大粗隆骨密度、第1~4腰椎骨密度、降钙素、甲状旁腺激素、骨钙素、肌酐、血清磷、血清钙差异未见统计学意义(P >0.05),治疗后观察组左股骨大粗隆骨密度、腰椎 L1-4骨密度明显升高、甲状旁腺激素有所降低,与治疗前及对照组比较差异有统计学意义(P 0. 05). After treatment in the observation group,left femoral trochanter BMD L1 - 4 lumbar spine BMD increased sig-nificantly,parathyroid hormone decreased,there were significant differences compared with before treat-ment and control group(P < 0. 05). There were no significant changes in other indicators. There were no serious adverse reactions. Conclusions Osteoporosis,calcium and vitamin D preparations conventional therapy,taking zoledronic acid plus can significantly improve patients’body and prevent adverse events. This path has important meaning in the protection of the quality of life.

  11. 鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症的成本-效果分析%Cost-effectiveness Analysis of Salmon Calcitonin and Zoledronic Acid in Treating Postmenopausal Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    白瑶; 周学琴; 刘玉琴

    2015-01-01

    Objective To study the cost-effectiveness of calcitonin salmon and zoledronic acid in treating postmenopausal osteoporo-sis.Methods 126casesofpostmenopausalosteoporosiswerecollectedandrandomlydividedintotwogroups:groupAandgroupB.Data was evaluated using the cost-effectiveness analysis of pharmacoeconomics.Results The costs of group A and group B were 2 279.42 and 3 316.79 yuan respectively.The total effective rates of group A and group B were 57.14%and 79.37%respectively.Group B was higher than those in group A,and the difference was statistically significant in two groups (P<0.05).The cost-effectiveness ratios (C/E) of group A and group B were 39.89 and 41.78 respectively.Conclusion Group B has better compliance and is more reasonable as compared with group A.%目的:比较鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症( PMOP)的成本与效果。方法将126例PMOP患者分为A组和B组,运用药物经济学原理进行成本-效果分析。结果 A组和B组的治疗成本分别为2279.43元和3316.79元;总有效率分别为57.14%和79.37%,B组明显高于A组,有统计学差异( P<0.05);经济学方面A组和B组的成本-效果比分别是39.89和41.79。结论应用唑来膦酸治疗绝经后骨质疏松症比鲑鱼降钙素更为合理。

  12. Trifluridine and Tipiracil Hydrochloride

    Science.gov (United States)

    This page contains brief information about trifluridine and tipiracil hydrochloride and a collection of links to more information about the use of this combination drug, research results, and ongoing clinical trials.

  13. Stereospecific ligands and their complexes. VI. The crystal structure of (S,S-ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S-H2eddp•HCl

    Directory of Open Access Journals (Sweden)

    VERICA V. GLODJOVIĆ

    2011-07-01

    Full Text Available (S,S-Ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S-H2eddp·HCl, was prepared and its crystal structure determined. The compound was characterized by infrared and 1H- and 13C-NMR spectroscopy. It forms P1 in the space group of a triclinic crystal system with a = 5.3902(2 Å, b = 5.8967(2 Å, c = 10.3319(2 Å, a = 99.625(2°, b = 91.645(2°, g = 109.995(2° and Z = 1.

  14. A contribution to the determination of aflatoxin B1, quinine hydrochloride and L(+)-ascorbic acid in foodstuffs by quantitative in situ thin-layer chromatographic analysis

    NARCIS (Netherlands)

    Beljaars, P.R.

    1974-01-01

    The application of quantitative thin-layer chromatography (TLC) involving in situ spectrodensitometric measurements with a flying-spot densitometer is described in this study for the analysis of aflatoxin B 1 , quinine hydrochloride

  15. Neuroprotective effect of penehyclidine hydrochloride on focal cerebral ischemiareperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Cuicui Yu; Junke Wang

    2013-01-01

    Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochloride in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of Bcl-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.

  16. Efficacy observation and safety analysis of Zoledronic acid on osteoporosis of postoperative gynaecological manligancies%唑来膦酸对妇科恶性肿瘤术后骨质疏松的疗效观察及安全性分析

    Institute of Scientific and Technical Information of China (English)

    张玉会; 李正英

    2016-01-01

    目的:观察唑来膦酸对妇科恶性肿瘤术后骨质疏松患者的疗效并进行不良反应监测与分析。方法选择2010年2月至2014年2月辽河油田总医院与海原县中医医院收治的120例妇科恶性肿瘤术后骨质疏松患者,采用随机双盲对照的研究设计将患者分为观察组与对照组,各60例。观察组予5mg唑来膦酸并服用钙尔奇D片,对照组给予5mg安慰剂并服用钙尔奇D片,比较两组治疗前后视觉模拟评分法( visual analogue scale/score,VAS)评分、腰椎与股骨颈骨密度以及急性期不良反应等情况。结果观察组VAS评分、腰椎与股骨颈骨密度均有显著改善(P<0.05),且效果明显优于对照组(P<0.05);观察组急性期不良反应发生率高达31.79%,但症状较轻且能较快缓解,并无严重不良反应。结论唑来膦酸对妇科恶性肿瘤术后骨质疏松的患者疗效明显,具有一定的安全性。%Objective To observe the curative effect as well as to monitor and analysis adverse reaction of osteoporosis treatment in patients with gynecological malignant tumor. Method 120 cases of patients who had come to the General Hospital of Liaohe Oil Field and Haiyuan County Hospital of Traditional Chinese Medicine from February 2010 to February 2014 were selected. Using randomized, double-blind and placebo-controlled study design, selected 120 cases after of gynecologic malignant tumor operation with osteoporosis. The observation group were given 5 mg of zoledronic acid with Caltrate D, the control group were given 5 mg placebo Caltrate D,Observe the two groups before and after treatment by VAS score, lumbar vertebra ,femoral neck bone mineral density and acute adverse reactions. Results After treatment,VAS score, lumbar spine and femoral neck bone mineral density were significantly improved (P<0. 05)in the observation group and were better than the control group (P<0. 05);acute stage adverse reaction rate in the observation group is as high

  17. Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

    Science.gov (United States)

    2016-11-10

    Ductal Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  18. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  19. Absorption Spectra of the 4f Electron Transitions of the Nd, Ho and and Er Complexes with 1-Cyclopyropyl-6-fluoro-1,4-dihydro-7-(4-ethyl-1-piperazin yl)-4-oxo-3-quinoline Carboxylic Acid Hydrochloride in the Presence of TX-100

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The absorption spectra of the neodymium, holmium and erbium complexes with l-cyclopropyl-6-fluoro-l,4-dihydro-7-(4-ethyl-l-piperazinyl)-4-oxo-3-quinoline carboxylic acid hydrochloride in the presence of TX-100 have been shown. The characteristic absorption bands of the 4f electron transitions of the complexes are enhanced markedly.

  20. Kinetic and analytical study on precipitation reactions with /sup 110/AgNO/sub 3/ of some di(. beta. -chloroethyl)amine derivatives and hydrochlorides with esters of N-(p-aminobenzoyl)-L-aspartic acid as carriers from dimethylformamide - water solution

    Energy Technology Data Exchange (ETDEWEB)

    Cecal, Al.; Sunel, V.; Ghimiciu, L. (Institutul Politehnic, Iasi (Romania))

    1983-01-01

    The kinetics of precipitation reactions with /sup 110/AgNO/sub 3/ of some di(..beta..-chloroethyl) amine derivates and hydrochlorides with esters of N-(p-aminobenzoyl)-L-aspartic acid as carriers in dimethylformamide-water mixture, were studied. The rate constants of these reactions were of the order of 10/sup -4/ lxmol/sup -1/xmin/sup -1/. The concentrations of the corresponding hydrochloride solutions were measured by radiometric titration with /sup 110/AgNO/sub 3/ solution of given concentration.

  1. Effect of matrine hydrochloride on liver injury

    Institute of Scientific and Technical Information of China (English)

    CHEN Li-bo; XU Feng; MA Wen-hui

    2008-01-01

    Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、 immunity liver injury of mice and chronic liver injury of rats. Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride (CCl4), thioacetamide(TAA), D-galactosamine(D-GalN), immunity hepatic injury model of mice induced by BCG and fat polysaccharide (LPS), chronic liver injury model of rats induced by CCI, were introduced in the experiment. The serum ALT and AST were measured in acute hepatic injury experiments. Serum ALT, AST, AKP, ALB, TP, BiL-T, ereatinine, triglyceride, sialie acid, larninin, hyaluronic acid, type Ⅲ proeollagen and type Ⅳ collagen, hepatic hydroxyproline (HyP) of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride. Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4, TAA and D-GaIN. The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment. Compared with the model group, the injection may obviously inhibited serum ALT, AST, TP, AKP, TRI, BiL-T, creatinine, triglyceride, sialic acid, laminin , hyaluronic acid , type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4, elevated ALB、A/G, reduced the liver HyP, decreased the index of the liver and the spleen. The liver visual observation, the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue, restrain the liver cell damage, reduce the pseudolobuli formation. Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and

  2. Simultaneous Estimation of Gemcitabine Hydrochloride and Capecitabine Hydrochloride in Combined Tablet Dosage Form by RP-HPLC Method

    Directory of Open Access Journals (Sweden)

    V. Rajesh

    2011-01-01

    Full Text Available A new reverse phase high performance liquid chromatography (RP-HPLC method has been developed for the simultaneous estimation of gemcitabine hydrochloride and capecitabine hydrochloride in combined tablet dosage form. An inertsil ODS-3 C-18 column having dimensions of 250×4.6 mm and particle size of 5 µm, with mobile phase containing a mixture of acetonitrile : water : triethyelamine in the ratio of (70 : 28 : 2v/v was used. The pH of mobile phase was adjusted to 4.0 with ortho-phosphoric acid. The flow rate was 1 mL/min and the column effluents were monitored at 260 nm. The retention time for gemcitabine hydrochloride and capecitabine hydrochloride was found to be 2.76 and 2.3 min respectively. The proposed method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The method was found to be linear in the range of 10-50 µg/mL and 4-24 µg/mL for gemcitabine hydrochloride and capecitabine hydrochloride, with regression coefficient r = 0.999 and r = 0.999, respectively.

  3. Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation.

    Science.gov (United States)

    Nada, Mohanad H; Wang, Hong; Workalemahu, Grefachew; Tanaka, Yoshimasa; Morita, Craig T

    2017-01-01

    Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture. Zoledronate inhibits farnesyl diphosphate synthase (FDPS) in monocytes causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ2Vδ2 cells. Because zoledronate inhibition of FDPS is also toxic for T cells, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Additionally, IL-15 increases the anti-tumor activity of murine αβ T cells in mice but its effect on the in vivo anti-tumor activity of human Vγ2Vδ2 cells has not been assessed. Human Vγ2Vδ2 T cells were expanded by pulse or continuous zoledronate stimulation with IL-2 or IL-15. Expanded Vγ2Vδ2 cells were tested for their expression of effector molecules and killing of tumor cells as well as their in vivo control of human prostate cancer tumors in immunodeficient NSG mice. Pulse zoledronate stimulation with either IL-2 or IL-15 resulted in more uniform expansion of Vγ2Vδ2 cells with higher purity and cell numbers as compared with continuous exposure. The Vγ2Vδ2 cells had higher levels of CD107a and perforin and increased tumor cytotoxicity. Adoptive immunotherapy with Vγ2Vδ2 cells derived by pulse stimulation controlled human PC-3 prostate cancer tumors in NSG mice significantly better than those derived by continuous stimulation, halting tumor growth. Although pulse zoledronate stimulation with IL-15 preserved early memory subsets, adoptive immunotherapy with IL-15-derived Vγ2Vδ2 cells equally inhibited PC-3 tumor growth as those

  4. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Arun MZ

    2016-04-01

    Full Text Available Mehmet Zuhuri Arun,1 Buket Reel,1 Graciela B Sala-Newby,2 Mark Bond,2 Aikaterini Tsaousi,2 Perry Maskell,2 Andrew C Newby21Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression.Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL plus TNF-α (10 ng/mL or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 µM or with apocynin (20 nM for 2 hours, then zoledronate (100 µM was added into 2% fetal calf serum containing medium for 24 hours.Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 µM increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by

  5. Determination of berberine hydrochloride and gallic acid in Suxiao Zhixie capsules by HPLC%HPLC-PDA法测定速效止泻胶囊中盐酸小檗碱的含量

    Institute of Scientific and Technical Information of China (English)

    何琳; 孙银华

    2011-01-01

    Aim To establish a method for the determination of berberine hydrochloride and gallic acid in Suxiao Zhixie capsules.Methods The separation was performed on SunfireTM C18column(5 μm,4. 6 mm × 150 mm) . The column temperature was 35 ℃ . The mobile phase was methonal-acetonitrile-0. 1%phasphoric acid( 3∶ 2 ∶ 95 ) and eluted with a gradient. The flow rate was 1. 0 ml · min -1·The injection volume was 20 μl, The detection wavelength was at 270 nm. Results The linear of berberine hydrochloride was in the range of 20. 931 - 209. 31 mg · L -1 ( r = 1. 000 0) . The average recovery was 100. 02% and RSD was 1. 5% ( n = 6) . The linear of gallic acid was in the range of 13. 075 - 130. 754μg · L-1 ( r = 1. 000 0). Conclusions The method is convenient , rapid, economical and accurate. It can be used for quality control of Suxiao Zhixie capsules.%目的 建立以高效液相色谱法测定速效止泻胶囊中盐酸小檗碱和没食子酸含量的方法.方法 采用SunfireTM C18(5 μm,4.6 mm×150 mm)色谱柱,柱温:35℃.流动相为甲醇-乙腈-0.1%磷酸(3:2:95),采用梯度洗脱程序,流速1.0 ml·min-1,进样量为20 μl,检测波长:270 nm.结果 盐酸小檗碱在20.931~209.31 mg·L-1范围内呈良好的线性关系,r=1.0000,平均回收率为100.02%,RSD=1.5%(n=6).没食子酸在13.075~130.754 mg·L-1范围内呈良好的线性关系,r=1.0000.结论 该方法简单、快速、准确、重现性好,能够较好地控制该产品的质量.

  6. Interaction between lidocaine hydrochloride (with and without adrenaline) and various irrigants: A nuclear magnetic resonance analysis

    Science.gov (United States)

    Vidhya, Nirmal; Karthikeyan, Balasubramanian Saravana; Velmurugan, Natanasabapathy; Abarajithan, Mohan; Nithyanandan, Sivasankaran

    2014-01-01

    Background: Interaction between local anesthetic solution, lidocaine hydrochloride (with and without adrenaline), and root canal irrigants such as sodium hypochlorite (NaOCl), ethylene diamine tetra-acetic acid (EDTA), and chlorhexidine (CHX) has not been studied earlier. Hence, the purpose of this in vitro study was to evaluate the chemical interaction between 2% lidocaine hydrochloride (with and without adrenaline) and commonly used root canal irrigants, NaOCl, EDTA, and CHX. Materials and Methods: Samples were divided into eight experimental groups: Group I-Lidocaine hydrochloride (with adrenaline)/3% NaOCl, Group II-Lidocaine hydrochloride (with adrenaline)/17% EDTA, Group III- Lidocaine hydrochloride (with adrenaline)/2% CHX, Group IV-Lidocaine hydrochloride (without adrenaline)/3% NaOCl, Group V-Lidocaine hydrochloride (without adrenaline)/17% EDTA, Group VI-Lidocaine hydrochloride (without adrenaline)/2% CHX, and two control groups: Group VII-Lidocaine hydrochloride (with adrenaline)/deionized water and Group VIII-Lidocaine hydrochloride (without adrenaline)/deionized water. The respective solutions of various groups were mixed in equal proportions (1 ml each) and observed for precipitate formation. Chemical composition of the formed precipitate was then analysed by nuclear magnetic resonance spectroscopy (NMR) and confirmed with diazotation test. Results: In groups I and IV, a white precipitate was observed in all the samples on mixing the respective solutions, which showed a color change to reddish brown after 15 minutes. This precipitate was then analysed by NMR spectroscopy and was observed to be 2,6-xylidine, a reported toxic compound. The experimental groups II, III, V, and VI and control groups VII and VIII showed no precipitate formation in any of the respective samples, until 2 hours. Conclusion: Interaction between lidocaine hydrochloride (with and without adrenaline) and NaOCl showed precipitate formation containing 2,6-xylidine, a toxic compound

  7. Interaction of articaine hydrochloride with prokaryotic membrane lipids.

    Science.gov (United States)

    Lygre, Henning; Moe, Grete; Nerdal, Willy; Holmsen, Holm

    2009-01-01

    Local anesthetics are the most commonly used drugs in dentistry, with a wide range of effects, including antimicrobial activity. High antimicrobial effects have recently been reported on oral microbes from articaine hydrochloride, revealed by the minimum inhibitory concentration and minimal bactericidal concentration. Additionally, articaine has recently been used as an alkaline component in endodontic materials with a proposed antibacterial activity. However, the detailed mechanisms of action have not been discussed. We determined the Langmuir surface pressure/molecular area isotherms of prokaryotic lipid monolayers, as well as the phospholipid phase transitions, by employing differential scanning calorimetry on unilamellar prokaryotic liposomes (bilayers). Articaine hydrochloride was found to interact with the prokaryotic membrane lipids in both monolayers and bilayers. An increase of the phospholipid molecular area of acidic glycerophospholipids as well as a decrease in phase transition temperature and enthalpy were found with increasing articaine hydrochloride concentration. The thermodynamic changes by adding articaine hydrochloride to prokaryotic membrane lipids are potentially related to the effects observed from antimicrobial peptides resulting from membrane insertion, aggregate composition, pore formation, and lysis. Interaction of articaine hydrochloride with prokaryotic membrane lipids is indicated. Hence, further research is necessary to gain insight into where these compounds exert their effects at the molecular level.

  8. Spectrophotometric estimation of pioglitazone hydrochloride in tablet dosage form

    Directory of Open Access Journals (Sweden)

    Basniwal Pawan

    2008-01-01

    Full Text Available Two simple, rapid, and precise methods - linear regression equation (LRE and standard absorptivity - were developed and validated for the estimation of pioglitazone hydrochloride in tablet dosage form. The maximum absorbance (lmax of pioglitazone hydrochloride was found to be 269.8 nm in methanol:water:hydrochloric acid (250:250:1. Beer-Lambert law was obeyed in the concentration range of 10-50 µg/ml, and the standard absorptivity was found to be 253.97 dl/g/cm. Both the methods were validated for linearity, accuracy, precision (days, analysts, and instrument variation, and robustness (solvent composition. The numerical values for all parameters lie within the acceptable limits. Pioglitazone hydrochloride was estimated in the range of 99.58-99.97% by LRE method and 100.25-100.75% by standard absorptivity method. At 99% confidence limit, the F-test value for the methods was found to be 1.8767.

  9. Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

    Science.gov (United States)

    Gómez-Clavel, José-Francisco; Gaitán-Cepeda, Luis-Alberto

    2017-01-01

    Background Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Material and Methods Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson’s trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. Results At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. Conclusions The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models. Key words:Bisphosphonates, osteonecrosis, dental extractions, animal model, BRONJ. PMID:28160593

  10. 三氯异氰尿酸与盐酸环丙沙星对蛋白核小球藻的毒性效应%Toxic effects of trichloroisocyanuric acid and ciprofloxacin hydrochloride on a freshwater alga, chlorella pyrenoidosa

    Institute of Scientific and Technical Information of China (English)

    聂湘平; 王翔; 陈菊芳; 鹿金雁; 李潇; 杨永涛

    2007-01-01

    测试了典型渔药三氯异氰尿酸(Trichloroisocyanuric acid,TCCA)、盐酸环丙沙星(Ciprofloxacin hydrochloride,CPFX)对蛋白核小球藻(Chlorella pyrenoidosa)的急性毒性及其Ⅰ相、Ⅱ相代谢酶活性的影响.结果表明,TCCA和CPFX作用小球藻96h后EC50分别为0.31 mg·L-1和20.61mg·L-1.TCCA在低浓度下对小球藻Ⅰ、Ⅱ相代谢酶GSH、GST、CAT和EROD都存在诱导作用,当TCCA浓度大于0.13 mg·L-1时,对GSH、GST和EROD的诱导减弱.GSH、GST、EROD三种酶对CPFX作用的响应较弱,当CPFX大于70.20mg·L-1时,GST受到显著抑制,而EROD则明显升高,与对照组差异显著,GSH没有明显变化.CAT对CPFX作用的响应较敏感,表现为典型适应性诱导现象"钟形曲线",适合作为CPFX暴露的生物标记物.

  11. pH- and sugar-sensitive multilayer films composed of phenylboronic acid (PBA)-modified poly(allylamine hydrochloride) (PBA-PAH) and poly(vinyl alcohol) (PVA): A significant effect of PBA content on the film stability.

    Science.gov (United States)

    Seno, Masaru; Yoshida, Kentaro; Sato, Katsuhiko; Anzai, Jun-ichi

    2016-05-01

    Multilayer thin films composed of phenylboronic acid (PBA)-modified poly(allylamine hydrochloride) (PAH), PBA-PAH, with different PBA contents were prepared to study the effect of PBA content on the stability of the films. An alternate deposition of PBA-PAH and poly(vinyl alcohol) (PVA) on the surface of a quartz slide afforded multilayer films through forming boronate ester bonds between PBA-PAH and PVA. The 10-layered (PBA-PAH/PVA)10 films constructed using PBA-PAHs containing 16% and 26% PBA residues were stable in aqueous solutions over the range of pH 4.0-10.0, whereas the multilayer films composed of PBA-PAHs with 5.9% and 8.3% PBA decomposed at pH 8.0 or lower. The pH-sensitive decomposition of the films was rationalized based on the destabilization of the boronate ester bonds in neutral and acidic solutions. In addition, the (PBA-PAH/PVA)10 films decomposed in glucose and fructose solutions as a result of competitive binding of sugars to PBA-PAH in the films. The sugar response of the films depended on the PBA content in PBA-PAH. The (PBA-PAH/PVA)10 films consisting of 16% and 26% PBA-substituted PBA-PAHs are sensitive to physiological relevant level of glucose at pH7.4 while stable in glucose-free solution, suggesting a potential use of the films in constructing glucose-induced delivery systems.

  12. Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH-sensitive acrylic acid-polyvinyl alcohol hydrogel

    National Research Council Canada - National Science Library

    Akhtar, Muhammad Faheem; Ranjha, Nazar Muhammad; Hanif, Muhammad

    2015-01-01

    The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid-polyvinyl alcohol hydrogel...

  13. 21 CFR 582.5676 - Pyridoxine hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5676 Pyridoxine hydrochloride. (a) Product. Pyridoxine hydrochloride....

  14. Simultaneous determination of a ternary mixture of doxylamine succinate, pyridoxine hydrochloride, and folic acid by the ratio spectra-zero-crossing, double divisor-ratio spectra derivative, and column high-performance liquid chromatographic methods.

    Science.gov (United States)

    Pathak, Ashutosh; Rajput, Sadhana J

    2008-01-01

    Three simple, rapid, and accurate methods, i.e., the derivative ratio spectra-zero-crossing method (method I), double divisor-ratio spectra derivative method (method II), and column reversed-phase high-performance liquid chromatographic (RP-HPLC) method (method III) were developed for the simultaneous determination of doxylamine succinate (DOX), pyridoxine hydrochloride (PYR), and folic acid (FA) in their ternary mixtures and in tablets. In methods I and II, the calibration graphs were linear in the range of 2.5-80, 1.0-40, and 1.0-30 microg/mL for DOX, PYR, and FA, respectively. In the HPLC method, the separation of these compounds was performed using mobile phase consisting of 0.05 M phosphate buffer (pH 6.3)-methanol-acetonitrile (50 + 20 + 30, v/v/v), and UV detection was performed at 263 nm. Linearity was observed between the concentrations of the analytes and peak areas [correlation coefficient (r) > or =0.9998] in the concentration range of 1.0-200, 4.0-600, and 4.0-600 microg/mL for DOX, PYR, and FA, respectively. The standard deviation of retention time in method III was 0.011, 0.015, and 0.016 for DOX, PYR, and FA, respectively. The precision studies for all of the methods gave relative standard deviation values of <2%. The results obtained from the methods were statistically compared by means of Student's t-test and the variance ratio F-test. It was concluded that all of the developed methods were equally accurate, sensitive, and precise. These methods could be applied to determine DOX, PYR, and FA in their combined dosage forms.

  15. Study on the syhthesis process of tetracaine hydrochloride

    Science.gov (United States)

    Li, Wenli; Zhao, Jie; Cui, Yujie

    2017-05-01

    Tetrachloride hydrochloride is a local anesthetic with long-acting ester, and it is usually present in the form of a hydrochloride salt. Firsleb first synthesized the tetracaine by experiment in 1928, which is one of the recognized clinical potent anesthetics. This medicine has the advantages of stable physical and chemical properties, the rapid role and long maintenance. Tetracaine is also used for ophthalmic surface anesthesia as one of the main local anesthetic just like conduction block anesthesia, mucosal surface anesthesia and epidural anesthesia. So far, the research mainly engaged in its clinical application research, and the research strength is relatively small in the field of synthetic technology. The general cost of the existing production process is high, and the yield is low. In addition, the reaction time is long and the reaction conditions are harsh. In this paper, a new synthetic method was proposed for the synthesis of tetracaine hydrochloride. The reaction route has the advantages of few steps, high yield, short reaction time and mild reaction conditions. The cheap p-nitrobenzoic acid was selected as raw material. By esterification with ethanol and reaction with n-butyraldehyde (the reaction process includes nitro reduction, aldol condensation and hydrogenation reduction), the intermediate was transesterified with dimethylaminoethanol under basic conditions. Finally, the PH value was adjusted in the ethanol solvent. After experiencing 4 steps reaction, the crude tetracaine hydrochloride was obtained.

  16. Effects of pantothenic acid on growth performance and carcass characteristics of growing-finishing pigs fed diets with or without ractopamine hydrochloride.

    Science.gov (United States)

    Groesbeck, C N; Goodband, R D; Tokach, M D; Dritz, S S; Nelssen, J L; DeRouchey, J M

    2007-10-01

    Two experiments evaluated effects of added pantothenic acid on performance of growing-finishing pigs. In Exp. 1, 156 pigs (PIC, initial BW = 25.7 kg) were used in a 3 x 2 x 2 factorial to evaluate the effects of added pantothenic acid (PA; 0, 22.5, or 45 ppm), ractopamine.HCl (RAC; 0 or 10 mg/kg), and sex on growth performance and carcass traits. Pigs were fed increasing PA from 25.7 to 123.6 kg (d 0 to 98) and RAC for the last 28 d before slaughter. Increasing the amount of added PA had no effect (P > 0.40) on ADG, ADFI, or G:F from d 0 to 70. A PA x sex interaction (P 0.38) on carcass traits. Added RAC increased (P PIC, initial BW = 40.4 kg, final BW = 123.6 kg) were used to determine the effects of increasing PA on growth performance and carcass characteristics of growing-finishing pigs reared in a commercial finishing facility. Pigs were fed 0, 22.5, 45.0, or 90 mg/kg of added PA. Increasing the amount of added PA had no effect (P > 0.45) on ADG, ADFI, or G:F, and no differences were observed (P > 0.07) for carcass traits. In summary, adding dietary PA to diets during the growing-finishing phase did not provide any advantages in growth performance or carcass composition of growing-finishing pigs. Furthermore, it appears that the pantothenic acid in corn and soybean meal may be sufficient to meet the requirements of 25- to 120-kg pigs.

  17. Stability of cefozopran hydrochloride in aqueous solutions.

    Science.gov (United States)

    Zalewski, Przemysław; Skibiński, Robert; Paczkowska, Magdalena; Garbacki, Piotr; Talaczyńska, Alicja; Cielecka-Piontek, Judyta; Jelińska, Anna

    2016-01-01

    The influence of pH on the stability of cefozopran hydrochloride (CZH) was investigated in the pH range of 0.44-13.00. Six degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The degradation of CZH as a result of hydrolysis was a pseudo-first-order reaction. As general acid-base hydrolysis of CZH was not occurred in the solutions of hydrochloric acid, sodium hydroxide, acetate, borate and phosphate buffers, kobs = kpH because specific acid-base catalysis was observed. Specific acid-base catalysis of CZH consisted of the following reactions: hydrolysis of CZH catalyzed by hydrogen ions (kH+), hydrolysis of dications (k1H2O), monocations (k2H2O) and zwitter ions (k3H2O) and hydrolysis of zwitter ions (k1OH-) and monoanions (k2OH-) of CZH catalyzed by hydroxide ions. The total rate of the reaction was equal to the sum of partial reactions: [Formula: see text]. CZH similarly like other fourth generation cephalosporin was most stable at slightly acidic and neutral pH and less stable in alkaline pH. The cleavage of the β-lactam ring resulting from a nucleophilic attack on the carbonyl carbon in the β-lactam moiety is the preferred degradation pathway of β-lactam antibiotics in aqueous solutions.

  18. "Sustained release formulation of Metoclopramide Hydrochloride "

    Directory of Open Access Journals (Sweden)

    Dabbagh MA

    2000-08-01

    Full Text Available In this research, several formulations containing, an anti emetic agent (Metoclopramide hydrochloride, a hydrophilic polymer (hydroxypropylmethylcellulose and a hydrophobic polymer (ethylcellulose 10 cP were prepared by direct compression. Different factors such as: the effect of different ratios of the polymers, particle size, pressure force and differences of release in acidic and distilled water as media were investigated. After developing the ideal formulation, the effect of changing the ratio of drug in core: coating on the formulation was investigated. Coating of tablets with ethylcellulose, changed the release mechanism of drug and shifted it to near zero order release. The results showed that except when matrices were coated with ethylcellulose, drug release was proportioned to the square root of time, which might be due to the change of release pattern from matrix to reservoir system.

  19. Synthesis of /sup 14/C-Bucromarone succinate and hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Nicolas, C.; Verny, M.; Maurizis, J.-C.; Payard, M.; Faurie, M.

    1986-08-01

    /sup 14/C-Bucromarone, 2-(4-(3-N,N dibutylamino propoxy) 3,5-dimethyl benzoyl) chromone, was synthesized from (U-/sup 14/C) oxalic acid. The labelling takes place at the first step of the synthesis, giving /sup 14/C-Bucromarone succinate (specific activity 7.45 mCi/mmol) and /sup 14/C-Bucromarone hydrochloride (specific activity 7.5 mCi/mmol).

  20. Enantiospecific synthesis of (1- sup 3 H)-(+)-pseudoephedrine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Hill, J.A.; Scharver, J.D. (Burroughs Wellcome Co., Research Triangle Park, North Carolina (USA). Chemical Development Labs.)

    1990-06-01

    The naturally occurring dextrorotary enantiomer (+)-pseudoephedrine was synthesized in the ({sup 3}H)-labelled form with specific activity 17.5 Ci/mmol suitable for development of a radioimmunoassay procedure. The chirally specific route from L-alanine to (1-{sup 3}H)-d-pseudoephedrine hydrochloride was based on the use of {alpha}-amino acids as chiral educts for asymmetric products. (author).

  1. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    Directory of Open Access Journals (Sweden)

    Pallavi Yerramsetty

    2012-03-01

    Full Text Available Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by using different enteric polymers. Protection of drug from acidic environment is done by coating the drug with enteric polymers by using suspension layering technique in Fluidized bed processor (FBP with different enteric polymers like HPMCAS (Hydroxy Propyl Methyl Cellulose Acetate Succinate, Acryl EZE and HPMCP (Hydroxy propyl methyl cellulose phthalate.The formulation (E12 of delayed release capsules of Duloxetine Hydrochloride containing HPMCP (HP-55: HP- 50 as enteric polymer can be taken as optimized

  2. Stability-indicating HPLC method for simultaneous determination of montelukast and fexofenadine hydrochloride

    Directory of Open Access Journals (Sweden)

    Mona Pankhaniya

    2013-01-01

    Full Text Available A simple, specific, accurate, and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of montelukast and fexofenadine hydrochloride, using a Lichrospher ® 100, RP-18e column and a mobile phase composed of methanol:0.1% o-phosphoric acid (90:10 v/v, pH 6.8. The retention times of montelukast and fexofenadine hydrochloride were found to be 10.16 and 12.03 min, respectively. Linearity was established for montelukast and fexofenadine hydrochloride in the range of 2-10 μg/ml and 24-120 μg/ml, respectively. The percentage recoveries of montelukast and fexofenadine hydrochloride were found to be in the range of 99.09 and 99.81%, respectively. Both the drugs were subjected to acid and base hydrolysis, oxidation, photolytic, and thermal degradation conditions. The degradation products of montelukast and fexofenadine hydrochloride were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of montelukast and fexofenadine hydrochloride in bulk drugs and formulations.

  3. Cartap hydrochloride poisoning: A clinical experience

    OpenAIRE

    Hari K Boorugu; Anugrah Chrispal

    2012-01-01

    Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular to...

  4. 21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride with promazine... RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222b Ketamine.... Ketamine hydrochloride, (±),-2-(o-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride, with promazine...

  5. Thermoanalytical Investigation of Terazosin Hydrochloride

    OpenAIRE

    Mona Mohamed Abdel-Moety; Ali Kamal Attia

    2013-01-01

    Purpose: Thermal analysis (TGA, DTG and DTA) and differential scanning calorimetry (DSC) have been used to study the thermal behavior of terazosin hydrochloride (TER). Methods: Thermogravimetric analysis (TGA/DTG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) were used to determine the thermal behavior and purity of the used drug. Thermodynamic parameters such as activation energy (E*), enthalpy (∆H*), entropy (∆S*) and Gibbs free energy change of the decomp...

  6. Electrochemical Behavior and Determination of Pyridoxine Hydrochloride at the Poly Nicotinic Acid Modified Electrode%盐酸吡哆辛在聚烟酸修饰电极上的电化学行为及测定

    Institute of Scientific and Technical Information of China (English)

    顾小燕; 唐鹏鹏; 李宁波; 刘欢; 俞静; 何凤云

    2014-01-01

    采用电聚合方法制备了聚烟酸修饰玻碳电极(PNA/GCE),并利用循环伏安法(CV)和差分脉冲伏安法(DPV)考察了盐酸吡哆辛(VB6)在该修饰电极上的电化学行为。结果表明,VB6在 PNA/GCE 上的氧化峰电流显著提高,电极反应为扩散控制的一电子两质子反应。利用差分脉冲伏安法对 VB6进行测定,线性范围为0.08~400μmol/L,VB6的检出限为0.02μmol/L,测定结果的相对标准偏差为3.1%(n=8),加标回收率为95.8%~103.7%。该方法可用于 VB6片中 VB6含量的测定。%Poly(nicotinic acid) modified electrode (PNA/GCE) was prepared and the electrochemical behavior of pyridoxine hydrochloride(VB6) was investigated at the modified electrode by cyclic voltammetry(CV) and differential pulse voltammetry(DPV). Results showed that the oxidation current of VB6 at the PNA/GCE was obviously larger than that at GCE. The oxidation process of VB6 was an irreversible diffusion–controlled process involving one electron and two protons. The liner range between the peak current of DPV and the concentration of VB6 was 0.08–400 μmol/L, and the detection limit was 0.02 μmol/L. The modified electrode showed a good reproducibility with a relative standard deviation of 3.1%(n=8). The recoveries were between 95.8% and 103.7%. The method can be applied to the analysis of vitamin B6 content in vitamin B6 tablets.

  7. [Clinical evaluation of roxatidine acetate hydrochloride injection as preanesthetic medication].

    Science.gov (United States)

    Kawanishi, M; Enomoto, A; Shimada, Y; Kurokawa, Y

    1991-09-01

    The effects of single intravenous administration of roxatidine acetate hydrochloride 75 mg on the volume and pH of gastric juice were investigated in 43 patients undergoing elective surgery under general anesthesia. The drug was given 1 hour before anesthesia. The percentages of patients with gastric pH above 2.5 and gastric juice volume under 25 ml were 95.3% and 97.7% at the time of induction of anesthesia and at the time of extubation, respectively. As for overall assessment on gastric secretion, 93.0% was judged as very effective. In 2 cases, pricking sensations were observed at the time of injection, but these symptoms disappeared without any treatment within a few minutes. No other adverse reactions nor abnormal laboratory test findings were observed. In conclusion, roxatidine acetate hydrochloride administered intravenously 1 hour prior to anesthesia is thought to be useful to prevent acid aspiration pneumonitis.

  8. Thermal Analysis Applied to Verapamil Hydrochloride Characterization in Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    Maria Irene Yoshida

    2010-04-01

    Full Text Available Thermogravimetry (TG and differential scanning calorimetry (DSC are useful techniques that have been successfully applied in the pharmaceutical industry to reveal important information regarding the physicochemical properties of drug and excipient molecules such as polymorphism, stability, purity, formulation compatibility among others. Verapamil hydrochloride shows thermal stability up to 180 °C and melts at 146 °C, followed by total degradation. The drug is compatible with all the excipients evaluated. The drug showed degradation when subjected to oxidizing conditions, suggesting that the degradation product is 3,4-dimethoxybenzoic acid derived from alkyl side chain oxidation. Verapamil hydrochloride does not present the phenomenon of polymorphism under the conditions evaluated. Assessing the drug degradation kinetics, the drug had a shelf life (t90 of 56.7 years and a pharmaceutical formulation showed t90 of 6.8 years showing their high stability.

  9. SYNTHESIS OF 2, 6-DIAMINO-3-PHENYLAZOPYRIDINE-1-OXIDE AND ITS HYDRO-CHLORIDE

    Directory of Open Access Journals (Sweden)

    Ganesh Babu Talagadadeevi, Ramakrishna Muvva, Bangar Reddy Vancha and Madhusudana Rao Jampani*

    2013-11-01

    Full Text Available The compound 2, 6-diamino-3-phenylazopyridine hydrochloride salt is a genito-urinary antiseptic drug under the trade name Pyridinium. This study is directed towards the occurrence of an oxidation reaction to convert the tertiary amine present in 2, 6-diamino-3-phenylazopyridine hydrochloride to form an N-oxide derivative as an impurity in the process for its preparation. This was done by the independent synthesis of 2, 6-diamino-3-phenylazopyridine-1-oxide hydrochloride salt by two independent routes. The presence of three amine functions in the molecule required first to protect the primary amine groups by derivatisation so that oxidation occurs exclusively at the tertiary amino group of the pyridine ring. 2, 6-diamino-3-phenylazopyridine was acetylated to get 2, 6-diacetamido-3-phenylazopyridine whose structure was confirmed from 1H NMR and mass spectral data. The oxidation of diacetyl derivative with peracetic acid resulted not only in the N-oxide formation but also in the cleavage of one of the acetamido group to give 2(6-acetamido-6(2amino-3-phenylazopyridine-1-oxide. The alkaline hydrolysis of the N-oxide form gave 2, 6-diamino-3-phenylazopyridine-1-oxide which on treatment with hydrochloric acid gave 2, 6-diamino-3-phenylazopyridine-1-oxide hydrochloride. In yet another route the N-oxide was prepared by the coupling reaction between benzene diazonium chloride and 2, 6-diaminopyridine-1-oxide in aqueous hydrochloric acid medium. This reaction resulted in the formation of 2, 6-diamino-3- phenylazopyridine-1-oxide hydrochloride as an insoluble salt. The structure of the N-oxide was confirmed from 1H NMR and mass spectral data. A co-injection HPLC analysis showed the complete absence of 2, 6-diamino-3-phenylazopyridine-1-oxide hydrochloride in 2, 6-diamino-3-phenylazopyridine hydrochloride in its manufacturing process.

  10. Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

    Science.gov (United States)

    Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel

    2014-11-01

    This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.

  11. The Regulation of Matrix Metalloproteinase Expression and the Role of Discoidin Domain Receptor 1/2 Signalling in Zoledronate-treated PC3 Cells.

    Science.gov (United States)

    Reel, Buket; Korkmaz, Ceren Gonen; Arun, Mehmet Zuhuri; Yildirim, Gokce; Ogut, Deniz; Kaymak, Aysegul; Micili, Serap Cilaker; Ergur, Bekir Ugur

    2015-01-01

    Discoidin Domain Receptors (DDR1/DDR2) are tyrosine kinase receptors which are activated by collagen. DDR signalling regulates cell migration, proliferation, apoptosis and matrix metalloproteinase (MMP) production. MMPs degrade extracellular matrix (ECM) and play essential role in tumor growth, invasion and metastasis. Nitrogen-containing bisphosphonates (N-BPs) which strongly inhibit osteoclastic activity are commonly used for osteoporosis treatment. They also have MMP inhibitory effect. In this study, we aimed to investigate the effects of zoledronate in PC3 cells and the possible role of DDR signalling and downstream pathways in these inhibitory effects. We studied messenger RNA (mRNA) and protein expressions of MMP-2,-9,-8, DDR1/DDR2 type I procollagen (TIP) and mRNA levels of PCA-1, MMP-13 and DDR-initiated signalling pathway players including K-Ras oncogene, ERK1, JNK1, p38, AKT-1 and BCLX in PC3 cells in the presence or absence of zoledronate (10-100 μM) for 2-3 days. Zoledronate (100 μM) down-regulated DDR1/ DDR2, TIP mRNAs but did not change MMP-13 (collagenase-3) mRNA. However, zoledronate up-regulated MMP-8 (collagenase-2) mRNA. Zoledronate also inhibited mRNA expressions of K-Ras, ERK1, AKT-1, BCLX and PCA-1; but did not change JNK1, p38 mRNA levels. Zoledronate (100 μM) supressed DDR1/DDR2, TIP expressions; and gelatinase (MMP-2/MMP-9) expressions/activities. Conversely, zoledronate up-regulated MMP-8 expression in PC3 cells. Zoledronate down-regulates MMP-2/-9 expressions in PC3 prostate cancer cells. DDR1/DDR2 signalling and DDR-initiated downstream Ras/Raf/ERK and PI3K/AKT pathways may at least partially responsible for MMP inhibitory effect of zoledronate.

  12. HPLC Simultaneous Determination of Glucosamine Hydrochloride and Glucosaminic Acid in Catalytic Reaction Solution%高效液相色谱法同时测定催化反应液中氨基葡萄糖盐酸盐和氨基葡萄糖酸

    Institute of Scientific and Technical Information of China (English)

    肖静静; 吴婷婷; 顾文秀; 杨盼; 李炜

    2013-01-01

    向制备氨基葡萄糖酸的催化反应液中加入亚硝酸盐试剂,在25℃下衍生反应5 min,所得含有氨基葡萄糖盐酸盐和氨基葡萄糖酸衍生物的溶液用作高效液相色谱分析.选用AminexHPX-87H离子排斥色谱柱为固定相,以5 mmol·L1硫酸溶液为流动相进行淋洗,用示差折光检测器进行检测,提出了同时测定氨基葡萄糖盐酸盐和氨基葡萄糖酸的高效液相色谱法.2种化合物的色谱峰面积与其浓度均在50 mmol·L-1以内呈线性关系,检出限(3S/N)依次为0.014,0.034 mmol·L-1.方法用于5批催化反应液中氨基葡萄糖盐酸盐和氨基葡萄糖酸的测定,加标回收率依次在99.3%~100%,99.2%~102%之间;测定值的相对标准偏差均小于2.5%.%The catalytic reaction solution used for preparation of glucosaminic acid was mixed with NaNCi as derivatizing reagent, and derivatized for 5 min at 25 ℃ The solution containing derivatives of glucosamine hydrochloride and glucosaminic acid was used for HPLC analysis, using Aminex HPX-87H ion replusive column as stationary phase and 5 mmol · L-1 H2SO4 solution as mobile phase in isocratic elution. Differential refractive index detector was adopted in the determination. Linear relationships between values of peak area and concentration of the 2 compounds were obtained in the same range within 50 mmol · L-1 , with detection limits (3S/N) 0. 014 mmol · L-1(for glucosamine hydrochloride) and 0. 034 mmol· L-1 (for glucosaminic acid). The proposed method was applied to the determination of glucosamine hydrochloride and glucosaminic acid in catalytic reaction solution, giving values of recovery in the ranges of 99. 3% —100% and 99. 2% —102% with RSD's less than 2. 5%.

  13. Thermoanalytical Investigation of Terazosin Hydrochloride

    Directory of Open Access Journals (Sweden)

    Mona Mohamed Abdel-Moety

    2013-02-01

    Full Text Available Purpose: Thermal analysis (TGA, DTG and DTA and differential scanning calorimetry (DSC have been used to study the thermal behavior of terazosin hydrochloride (TER. Methods: Thermogravimetric analysis (TGA/DTG, differential thermal analysis (DTA and differential scanning calorimetry (DSC were used to determine the thermal behavior and purity of the used drug. Thermodynamic parameters such as activation energy (E*, enthalpy (H*, entropy (S* and Gibbs free energy change of the decomposition (G* were calculated using different kinetic models. Results: The purity of the used drug was determined by differential scanning calorimetry (99.97% and specialized official method (99.85% indicating to satisfactory values of the degree of purity. Thermal analysis technique gave satisfactory results to obtain quality control parameters such as melting point (273 ºC, water content (7.49% and ash content (zero in comparison to what were obtained using official method: (272 ºC, (8.0% and (0.02% for melting point, water content and ash content, respectively. Conclusion: Thermal analysis justifies its application in quality control of pharmaceutical compounds due to its simplicity, sensitivity and low operational costs. DSC data indicated that the degree of purity of terazosin hydrochloride is similar to that found by official method.

  14. Efficacy of vinorelbine and zoledronate combination therapy against postoperative recurrence of lung cancer.

    Science.gov (United States)

    Ishida, Junzo; Furukawa, Kinya; Hosaka, Makoto; Saito, Makoto; Matsushima, Yasushi

    2012-04-01

    We report a case of a response to long-term treatment with vinorelbine and zoledronate in a patient with lymph node and multiple bone metastases after lung cancer surgery. The patient was a 70-year-old male initially examined by a local physician for an abnormal shadow that had been detected on a chest X-ray during a screening examination. CT revealed a mass shadow measuring 28 mm in diameter in the left S10, and because lung cancer was suspected, the patient was admitted to our hospital for the first time and examined. Lung cancer was diagnosed intraoperatively, and left lower lobectomy was performed. The pathological stage was III a, and postoperative adjuvant chemotherapy was performed, but recurrences in the form of lymph node and multiple bone metastases were detected. After diagnosis of the recurrence, the patient was treated with long-term vinorelbine (VNR)biweekly and zoledronate (ZOL) monthly, and a response was obtained. A patient with postoperative recurrence of lung cancer associated with multiple bone metastases responded to combination chemotherapy with VNR and ZOL. VNR was effective against postoperative recurrence in an elderly lung cancer patient with complications, and could be administered safely long-term. ZOL also had a favorable protective effect against skeletal-related events (SREs) in lung cancer, and the results suggested that it also had an antitumor effect in this patient.

  15. Intra-tumor delivery of zoledronate mitigates metastasis-induced osteolysis superior to systemic administration

    Directory of Open Access Journals (Sweden)

    Anas Nooh

    2017-03-01

    Full Text Available Bisphosphonates (BPs have recently been shown to have direct anti-tumor properties. Systemic treatment with BPs can have multiple adverse effects such as osteonecrosis of the jaw and BP induced bone fracturing and spine instability. While benefits of systemic BP treatments may outweigh risks, local treatment with BPs has been explored as an alternate strategy to reduce unwarranted risk. In the present study, we examined whether local delivery of BPs inhibits tumor-induced osteolysis and tumor growth more effectively than systemic treatment in an animal model of tumor-induced bone disease. Following establishment of an intra-tibial model of bone metastases in athymic mice, the experimental group was treated by local administration of zoledronate into the tibial lesion. A comparison of the effect of local versus systemic delivery of zoledronate on the formation of tumor-induced osteolysis was also carried out. A significant increase in mean bone volume/tissue volume % (BV/TV of the locally treated group (12.30±2.80% compared to the control group (7.13±1.22% (P<0.001. Additionally, there was a significant increase in the BV/TV (10.90±1.25% in the locally treated group compared to the systemically treated group (7.53±0.75% (P=0.005. These preliminary results suggest that local delivery of BPs outperforms both systemic and control treatments to inhibit tumor-induced osteolysis.

  16. Acute Psychotic Symptoms due to Benzydamine Hydrochloride Abuse with Alcohol

    Directory of Open Access Journals (Sweden)

    Yahya Ayhan Acar

    2014-01-01

    Full Text Available Benzydamine hydrochloride is a locally acting nonsteroidal anti-inflammatory drug. Benzydamine hydrochloride overdose can cause stimulation of central nervous system, hallucinations, and psychosis. We presented a young man with psychotic symptoms due to benzydamine hydrochloride abuse. He received a total dose of 1000 mg benzydamine hydrochloride with alcohol for its hallucinative effects. Misuse of benzydamine hydrochloride must be considered in differential diagnosis of first-episode psychosis and physicians should consider possibility of abuse in prescribing.

  17. Spectrophotometric simultaneous estimation of ranitidine hydrochloride and ondansetron hydrochloride from tablet formulation

    Directory of Open Access Journals (Sweden)

    Pillai S

    2007-01-01

    Full Text Available Three simple, accurate, economical and reproducible UV spectrophotometric methods for simultaneous estimation of two component drug mixture of ranitidine hydrochloride and ondansetron hydrochloride from combined tablet dosage form have been developed. First developed method involves formation and solving of simultaneous equations at 267.2 nm and 314.4 nm. Second method was developed making use of first order derivative spectroscopy using 340.8 nm and 276.0 nm as zero crossing points for estimation of ranitidine hydrochloride and ondansetron hydrochloride respectively. Third method is based on two wavelength calculation, wavelengths selected for estimation of ranitidine hydrochloride were 266.1 nm and 301.8 nm and for ondansetron hydrochloride 305.7 nm and 319.2 nm. The results of analysis have been validated statistically and by recovery studies.

  18. Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine.

    Science.gov (United States)

    Shamsa, F A; Maghssoudi, R H

    1976-05-01

    A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference.

  19. 口服盐酸氨基葡萄糖和注射透明质酸钠以及两者联合治疗膝关节骨性关节炎的临床研究%A Randomized Controlled Clinical Trial of Glucosamine Hydrochloride, Hyaluronic Acid and Combined Use in the Treatment of Knee Osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    姜丹生

    2012-01-01

    目的 评价口服盐酸氨基葡萄糖和注射透明质酸钠以及两者联合治疗膝关节骨性关节炎的疗效.方法 采用随机对照临床研究方法,将162例诊断为膝骨性关节炎的患者随机分为3组,口服组、注射组、联合用药组各54例,分别给予口服盐酸氨基葡萄糖480毫克/次,每天口服3次,关节内注射2毫升/次,每周1次.共治疗5周.停药后观察2周.收集3组患者治疗期间Lequesne指数评分和VAS评分,来评估治疗前后膝关节症状变化程度.结果 治疗5周后,口服组、注射组、联合用药组Lequesne总指数比治疗前均有明显下降,分别为3.3±1.6、3.1±1.3、2.8±1.3.联合用药组和其他两组差异具有统计学意义(P<0.05).VAS评分治疗5周后口服组、注射组、联合用药组分别下降为1.77±0.91、1.66±1.21、1.53±1.13.与治疗前相比均具有统计学差异(P<0.05).结论 口服盐酸氨基葡萄糖和关节内注射透明质酸钠均对膝骨性关节炎具有良好的疗效,两者联合治疗方式效果优于单独用药治疗方式.%Objective To evaluate the efficacy of glucosamine hydrochloride,hyaluronic acid and combined use of the two drugs in the treatment of patients with knee osteoarthritis. Methods Totally 162 patients suffering from knee osteoarthritis were random divided into 3 groups, and were treated with glucosamine hydrochloride, hyaluronic acid and combined of above two therapies. Patients reveived medicine 3 times daily with total 480mg/d for glucosamine hydrochloride group, intra - articular injection of hyaluronic acid one time a week with 2ml per time and two treatments combined for combined group. Lequesne index and VAS score were recorded at 1,2,3,4,5 weeks during therapy and 1,2 weeks after therapy. Results Lequesne index were obviously decreased at 5 weeks for 3 groups. It was 3.3 ±1.6、3.1 ±1.3、2.8 ±1.3 , respectively. VAS scores were 1.77 ±0.91、1.66 ±1.21、1. 53 ± 1.13 at 5 weeks for 3 groups

  20. Stability Indicating HPLC Method for Simultaneous Quantification of Trihexyphenidyl Hydrochloride, Trifluoperazine Hydrochloride and Chlorpromazine Hydrochloride from Tablet Formulation

    Directory of Open Access Journals (Sweden)

    P. Shetti

    2010-01-01

    Full Text Available A new, simple, precise, rapid, selective and stability indicating reversed-phase high performance liquid chromatographic (HPLC method has been developed and validated for simultaneous quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and chlorpromazine hydrochloride from combined tablet formulation. The method is based on reverse-phase using C-18 (250×4.6 mm, 5 μm particle size column. The separation is achieved using isocratic elution by methanol and ammonium acetate buffer (1% w/v, pH 6.5 in the ratio of 85:15 v/v, pumped at flow rate 1.0 mL/min and UV detection at 215 nm. The column is maintained at 30 °C through out the analysis. This method gives baseline resolution. The total run time is 15 min. Stability indicating capability is established buy forced degradation experiment. The method is validated for specificity, accuracy, precision and linearity as per International conference of harmonisation (ICH. The method is accurate and linear for quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and Chlorpromazine hydrochloride between 5 - 15 μg/mL, 12.5- 37.5 μg/mL and 62.5 - 187.5 μg/mL respectively.

  1. High performance thin layer chromatographic method for simultaneous estimation of ibuprofen and pseudoephedrine hydrochloride

    Directory of Open Access Journals (Sweden)

    Chitlange S

    2008-01-01

    Full Text Available High performance thin layer chromatographic method is developed for simultaneous estimation of ibuprofen and pseudoephedrine hydrochloride in tablets. Silica gel 60F 254 plates were used as stationary phase and t.butanol: ethyl acetate: glacial acetic acid: water (7:4:2:2 v/v as mobile phase. Wavelength selected for analysis was 254 nm. Percent estimation of ibuprofen and pseudoephedrine hydrochloride was found to be 99.56% and 98.77%, respectively. Percent recovery for both the drugs was found in the range of 98.27% to 100.91%, respectively.

  2. A Novel Synthesis of Difloxacin Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Difloxacin hydrochloride, one of aryl-fluoro quinolone antibiotic, has been synthesized in seven steps from 2, 4-dichloro-5-fluoroacetophenone via oxalylation, ethoxymethylenation,amination, cyclization, hydrolysis, decarbonylation and N-methylpiperazination. Additional four new intermediates are produced.

  3. A novel asymmetric synthesis of cinacalcet hydrochloride

    OpenAIRE

    Arava, Veera R; Laxminarasimhulu Gorentla; Pramod K. Dubey

    2012-01-01

    A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described.

  4. A novel asymmetric synthesis of cinacalcet hydrochloride

    Directory of Open Access Journals (Sweden)

    Veera R. Arava

    2012-08-01

    Full Text Available A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described.

  5. A novel asymmetric synthesis of cinacalcet hydrochloride

    Science.gov (United States)

    Gorentla, Laxminarasimhulu; Dubey, Pramod K

    2012-01-01

    Summary A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. PMID:23019473

  6. Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in the China

    Science.gov (United States)

    Zhang, Jian Xin; Zhang, Da Ming; Han, Xu Guang

    2008-01-01

    A total of 48 methamphetamine hydrochloride samples from eight seizures were analyzed using gas chromatography–mass spectrometry (GC–MS) and a flame ionization detector (GC–FID). Major impurities detected include 1,2-dimethyl-3-phenylaziridine, Ephedrine/pseudoephedrine, 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene. These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the methamphetamine hydrochloride samples seized during 2006–2007. Additionally the presence of 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene is indicative that six seizures were synthesized via the more specific ephedrine/hydriodic acid/red phosphorus method. In addition, five impurities were found for the first time in methamphetamine hydrochloride samples. Seventeen impurity peaks were selected from the GC–FID chromatograms. The peak areas of the selected peaks were then grouped for cluster analysis. PMID:19008060

  7. Multi-walled carbon nanotubes based catalyst plasmon resonance light scattering analysis of tetracycline hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    It was found that multi-walled carbon nanotubes (MWNTs) could catalyze the redox reaction between chlorauric acid (HAuCl4) and reductive drugs such as tetracycline hydrochloride (TC), producing gold nanoparticles (Au NPs). By measuring the plasmon resonance light scattering (PRLS) signals of the resulting Au NPs, tetracycline hydrochloride can be detected simply and rapidly with a linear range of 4―26 μmol/L, a correlated coefficient (r ) of 0.9955, and a limit of detection (3σ) of 6.0 nmol/L. This method has been successfully applied to the detection of tetracycline hydrochloride tablets in clinic with the recovery of 101.9% and that of fresh urine samples with the recovery of 98.3%―102.0%.

  8. HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

    Institute of Scientific and Technical Information of China (English)

    齐美玲; 王鹏; 耿颖姝; 顾峻岭

    2003-01-01

    The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0.5% phosphoric acid solution (20∶30∶50,V/V/V) at a flow rate of 1.0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0.81-8.10 μg/mL. The mean recovery was 99.8% (SR=0.7%, n=9), and the precision was found to be 0.45% (n=9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

  9. Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.

    Science.gov (United States)

    Ranpise, Nisharani S; Korabu, Swati S; Ghodake, Vinod N

    2014-04-01

    Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 ± 1.5 mV. More than 70% lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... HUMAN SERVICES Food and Drug Administration Determination That SUBOXONE (Buprenorphine Hydrochloride and... (buprenorphine hydrochloride (HCl) and naloxone HCl) sublingual tablets, 2 milligrams (mg)/0.5 mg and 8 mg/2 mg... to approve abbreviated new drug applications (ANDAs) for buprenorphine HCl and naloxone...

  11. 盐酸表柔比星-聚乳酸-羟基乙酸共聚物纳米粒的制备%Study on Preparation of Epirubicin Hydrochloride Loaded Poly (L-Lactic-co-Glycolic Acid) Nanoparticles and the Effects in Vitro

    Institute of Scientific and Technical Information of China (English)

    宋晶晶; 李慧; 傅红兴; 纪建松

    2012-01-01

    目的 制备盐酸表柔比星-聚乳酸-羟基乙酸(PLGA)共聚物纳米粒,对其进行质量评价.方法 采用乳化-溶剂挥发法制备盐酸表柔比星纳米粒;对主要处方因素如PLGA用量、外水相中聚山梨酯-80用量、泊洛沙姆188和聚山梨酯-80比例进行正交设计,以药物的包封率、载药量和药物利用率等为考察指标.结果 采用优化后处方制得的纳米粒药物包封率为(32.6±1.2)%,载药量为(7.2±0.5)%,药物利用率为(51.6±3.4)%,纳米粒平均粒径166.6nm,药物可持续160h释放.结论 该方法制备盐酸表柔比星纳米粒工艺简单,无需使用聚乙烯醇,药物释放缓慢.%Objective To prepare epirubicin hydrochloride-loaded poly L-lactic-eo-glycolic acid (PLGA) nanoparticles and investigate the characteristics. Methods The epirubicin hydrochloride-loaded PLGA nanoparticles were prepared by double emulsion-solvent evaporation method. The main effective factors such as the amount of PLGA, Tween-80 in external water phase, and Ine ratio of poloxamer 188 to Tween-80 were orthogonally designed. Drag entrapment efficiency, drug loading rate and drug utilization were determined. Results By using the optimal formulation, the drug encapsulation efficiency of the nanoparticles was (32.6±1.2)% ; the drug loading was (7.2±0.5)% ; the drug utilization was (51.6±3.4)% ; the mean size of the nanoparticles was 166.6 ran; the drug release continued 160 hours. Conclusion Epirubicin hydrochloride-loaded PLGA nanoparticles are prepared successfully and simpiy without use of polyviol and display sustained drug release properties.

  12. [Clinical evaluation of roxatidine acetate hydrochlorides as a preanesthetic medication].

    Science.gov (United States)

    Namba, M; Chihara, E; Ibuki, T; Ashida, H; Fukushima, H; Tanaka, Y

    2001-02-01

    Roxatidine acetate hydrochloride capsule is slowly absorbed from the gastrointestinal tract, and its acid suppressive effect on the stomach is long-lasting compared with other H2-blockers. The reduction of gastric juice in perioperative period is considered advantageous for patients not only because it decreases the risk for aspiration pneumonia but also because it reduces the risk of bronchial spasm induced by gastroesophageal reflux of acidic gastric content. The effects of single oral administration of roxatidine acetate hydrochloride 150 mg at night before the operation on the volume and pH of gastric juice were investigated during anesthesia using two types of anesthetic agents (isoflurane and propofol) in 93 patients of three age groups (group Y: age 20-40, group M: age 41-64, group O: age 65 roxatidine on reduction of gastric juice was found at the time of anesthetic induction and 2 hours after the induction in any age group with either anesthetic agent. The serum concentration of roxatidine at the time of induction was much higher in group O. The value of residual concentration of roxatidine 20 hours after oral intake was estimated from the intraoperative measurements of serum concentration. The results suggest that single administration at night before the operation is sufficient for the oldest group, but an additive dose is recommended for the younger groups.

  13. Octenidine hydrochloride in hydatid disease.

    Science.gov (United States)

    Altindis, Mustafa; Arikan, Yuksel; Cetinkaya, Zafer; Polat, Coskun; Yilmaz, Sezgin; Akbulut, Gökhan; Dilek, Osman Nuri; Gokce, Ozcan

    2004-01-01

    Hydatid disease is still endemic in many devoloping countries and continues to be an important cause of morbidity. The objective of this study was to determine the in vitro scolicidal effects of octenidine hydrochloride in different concentrations using different exposure times. After hydatid cyst liquid was left to precipitate for 1 h to obtain cystic sand, various concentrations of octenidine (undiluted, 1% and 0.1% diluted) were added to concentrated hydatid cyst sediments for 5, 10, 15, 20, 25, 30, 45, and 60 min, and scolicidal effects of octenidine were compared with 20% saline and control group for the same times. It was found that undiluted octenidine had a strong scolicidal effect at 15 min compared to saline at 20%. One percent octenidine had a scolicidal effect at 30 min. However, 0.1% octenidine did not have enough scolicidal effect in 1 h. It was concluded that undiluted and 1% diluted octenidine might be used for scolicidal purpose in the treatment of hydatid disease.

  14. Zoledronate derivatives as potential inhibitors of uridine diphosphate-galactose ceramide galactosyltransferase 8: A combined molecular docking and dynamic study.

    Science.gov (United States)

    Pannuzzo, Giovanna; Graziano, Adriana Carol Eleonora; Pannuzzo, Martina; Masman, Marcelo Fabricio; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease is a neurodegenerative disorder caused by deficiency of galactocerebrosidase activity that affects the myelin sheath of the nervous system, involving dysfunctional metabolism of sphingolipids. It has no cure. Because substrate inhibition therapy has been shown to be effective in some human lysosomal storage diseases, we hypothesize that a substrate inhibition therapeutic approach might be appropriate to allow correction of the imbalance between formation and breakdown of glycosphingolipids and to prevent pathological storage of psychosine. The enzyme responsible for the biosynthesis of galactosylceramide and psychosine is uridine diphosphate-galactose ceramide galactosyltransferase (2-hydroxyacylsphingosine 1-β-galactosyltransferase; UGT8; EC 2.4.1.45), which catalyzes the transferring of galactose from uridine diphosphate-galactose to ceramide or sphingosine, an important step of the biosynthesis of galactosphingolipids. Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. From structural information on UGTs' active site stereochemistry, charge density, and access through the hydrophobic environment, the molecular docking procedure allowed us to identify zoledronate as a potential inhibitor of human ceramide galactosyltransferase. More importantly, zoledronate derivates were designed through computational modeling as putative new inhibitors. Experiments in vivo and in vitro have been planned to verify the possibility of using zoledronate and/or the newly identified inhibitors of UGT8 for a substrate inhibition therapy useful for treatment of Krabbe's disease and/or other lysosomal disorders. © 2016 Wiley Periodicals, Inc.

  15. Compound list: fluoxetine hydrochloride [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available fluoxetine hydrochloride FLX 00158 ftp://ftp.biosciencedbc.jp/archive/open-tggates/...LATEST/Human/in_vitro/fluoxetine_hydrochloride.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/o...pen-tggates/LATEST/Rat/in_vivo/Liver/Single/fluoxetine_hydrochloride.Rat.in_vivo.Liver.Single.zip ftp://ftp....biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/fluoxetine_hydrochloride.Rat.in_vivo.Liver.Repeat.zip ...

  16. Observation of the efficacy and safety of zoledronic and in postmenopausal osteoporosis%唑来膦酸治疗绝经后骨质疏松症的有效性和安全性

    Institute of Scientific and Technical Information of China (English)

    黄淑纾; 王军; 林华

    2016-01-01

    Objective:To investigate whether there is an effective attenuation of osteoporosis treatments on BMD in-crease and whether they are safe with increasing ages and increasing uses of zoledronic acid. To investigate whether there ’s any improvement of health-related quality of life (HRQL) as zoledronic acid improves BMD. Methods: In this self-control, prospective trial, 220 postmenopausal women with osteoporosis (mean age 67 years) received a single infusion of ZOL 5 mg at baseline in the 12th month. BMD and HRQL were measured at baseline, in the 12th and 24th month (before each use of zoledronic acid). The main outcome measures were the changes in lumbar spine and hip BMD and the changes in HRQL by the Short Form-36 questionaire (SF-36). The ANOVA and LSD multiple comparison was used for statistical comparison. Safety evaluation was conducted at the same time. Results: The patients with postmenopausal osteoporosis had significantly higher L1-4 (0.841 ±0.134), total hip (0.730 ±0.096), femoral neck (0.695 ±0.073), Ward’s triangle (0.498 ±0.036) and trochanter (0.559±0.056) BMD (P<0.05) and improved BP, GH and PCS in HRQL (P<0.05) over 2-year treatment of once-yearly ZOL 5mg. No serious adverse events directly related occurred. Conclusions: Zoledronic acid is safe and effective, increases bone mineral density substantially, and increases health-related quality of life, especially in the physical aspects, over 2 years of treatment in women with postmenopausal osteoporosis.%目的:探讨唑来膦酸(ZOL)治疗绝经后骨质疏松症的疗效和安全性。方法:采用自身对比前瞻性研究,220例绝经后骨质疏松症妇女在基线、12个月时接受单次静脉输注ZOL 5mg,在基线、12个月和24个月时使用双能X线(DXA)测定骨密度(BMD)、SF-36问卷表评估健康相关生活质量(HRQL),同时进行安全性观察。结果:经过2年ZOL治疗,患者L1-L4(0.841±0.134)、全髋(0.730±0.096

  17. The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

    Directory of Open Access Journals (Sweden)

    Glatt M.

    2001-01-01

    Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

  18. Zoledronic acid treatment for cancerous bone metastases: a phase IV study in Taiwan

    Directory of Open Access Journals (Sweden)

    Po-Hui Chiang

    2013-01-01

    Full Text Available Aim of study: To investigate the features, adverse effects, bone marker changes in patients with breast cancer, prostate cancer, and multiple myeloma with bone metastases under Zometa® therapy. Materials and Methods: This post-marketing study included 414 Taiwanese patients with bone metastases secondary to breast cancer, prostate cancer, or multiple myeloma who received Zometa® for 48 weeks. The patients′ characteristics, medication and adverse events were recorded, meanwhile changes in four serum bone metabolic markers and pain reduction were assessed every three months for one year. Results: A total of 3,711 doses of Zometa® were infused, accounting for 294.5 patient-years. Adverse events occurred in 9.4% of patients, with bone pain, insomnia, constipation, and pyrexia as the most frequently reported. There was no osteonecrosis of the jaw. The incidence of skeletal-related events decreased significantly from 44.9% to 18.8%. Serum NTx, BAP, and TRACP5b steadily decreased to nadir at six months, but serum OPG was persistently elevated until the end of one year. The average decrease in pain score was 14.1, 14.3, and 16.7 for prostate cancer, breast cancer, and multiple myeloma patients, respectively. Conclusion: Zometa® can be safely administered in Taiwanese patients with bone metastases secondary to breast cancer, prostate cancer, and multiple myeloma. There are concomitant decreases in skeletal-related events and bone pain.

  19. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  20. Atypical Subtrochanteric Femur Fracture in Patient with Metastatic Breast Cancer Treated with Zoledronic Acid

    OpenAIRE

    2012-01-01

    Several case series have suggested an association exists between atypical femoral subtrochanteric fractures and long-term use of bisphosphonates. It is thought that prolonged use of bisphosphonates may lead to adynamic, fragile bone. The radiologic features of atypical fractures include diffuse cortical thickening, transverse fracture, and beaking at the lateral subtrochanteric area. Atypical subtrochanteric femur fractures have been reported after use of alendronate, but there have been rare...

  1. Severe resistant hypocalcemia in multiple myeloma after zoledronic acid administration: a case report

    OpenAIRE

    Noriega Aldave, Adrian P; Jaiswal, Shikha

    2014-01-01

    Introduction Hypercalcemia is one of the most common metabolic abnormalities encountered in any form of malignancy. Hypocalcemia, however, is a rare manifestation, especially in cancers with bone involvement. Here we present a case of hypocalcemia in a patient with multiple myeloma that was refractory to treatment. Case presentation A 73-year-old African American woman recently diagnosed with multiple myeloma, presented with a 2-day history of fever, vomiting and hypocalcemia. Ten days prior ...

  2. FES-Rowing versus Zoledronic Acid to Improve Bone Health in SCI

    Science.gov (United States)

    2015-10-01

    Leslie R. Morse, DO Betty Diamond 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: lmorse4@partners.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION...bone strength of the lower extremity in a dose dependent fashion. Reportable Outcomes Publications Taylor JA, Picard G, Porter A, Morse LR

  3. Synthesis and Molecular Recognition of Novel Cyclic Pseudopeptides Containing L-Glutamic Acid or L-Aspartic Acid Backbones

    Institute of Scientific and Technical Information of China (English)

    WANG Tao王涛; HUANG Xiao-Yi黄小毅; XIA Chuan-Qin夏传琴; YU Xiao-Qi余孝其; XIE Ru-Gang谢如刚

    2004-01-01

    Novel cyclic pseudopeptides containing L-glutamic acid or L-aspartic acid backbone structures were efficiently synthesized and characterized. Their chiral recognition properties for L- and D-amino acid methyl ester hydrochloride were discussed also.

  4. Extractive determination of ephedrine hydrochloride and bromhexine hydrochloride in pure solutions, pharmaceutical dosage form and urine samples.

    Science.gov (United States)

    Abdel-Ghani, N T; Rizk, M S; Mostafa, M

    2013-07-01

    Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL(-1), using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ≥0.995 (n=6) with a relative standard deviation (RSD) ≤1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully.

  5. Extractive determination of ephedrine hydrochloride and bromhexine hydrochloride in pure solutions, pharmaceutical dosage form and urine samples

    Science.gov (United States)

    Abdel-Ghani, N. T.; Rizk, M. S.; Mostafa, M.

    2013-07-01

    Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL-1, using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ⩾0.995 (n = 6) with a relative standard deviation (RSD) ⩽1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully.

  6. [Simultaneous determination of five cold medicine ingredients in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets by pH/organic solvent double-gradient high performance liquid chromatography].

    Science.gov (United States)

    Xuan, Xueyi; Huang, Lina; Pan, Xiaoling; Li, Ning

    2013-02-01

    A pH/organic solvent double-gradient mode in reversed-phase high performance liquid chromatography (HPLC) has been established as a new approach to the simultaneous determination of acetaminophen, caffeine, salicylamide, pseudoephedrine hydrochloride and triprolidine hydrochloride in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets. Through the optimization of the organic solvent gradient mode and pH/organic solvent double-gradient mode, the optimum double-gradient HPLC system of the five cold medicine ingredients has been built. The determination was carried out on a Diamonsiol C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase consisted of methanol, 0.05 mol/L ammonium acetate solution and 0.08 mol/L acetic acid solution. The column temperature was set at 30 degrees C. The flow rate was 1.0 mL/min. The sample was measured at multiple wavelengths: 0-6 min, 280 nm; 6-7 min, 257 nm; 7-14 min, 280 nm; 14 min, 233 nm. The separation of the five cold medicine ingredients in the tablets was achieved in 25.5 min. The linear ranges of acetaminophen, pseudoephedrine hydrochloride, caffeine, salicylamide and triprolidine hydrochloride were 0.055 -0.998 g/L, 0.053-0.946 g/L, 0.007-0.129 g/L, 0.035-0.622 g/L and 0.002-0.039 g/L, respectively, with their correlation coefficients greater than 0.999 0. The detection limits (S/N = 3) were 0.09, 6, 0.02, 0.128 and 0.02 mg/L, respectively. Their mean recoveries were 97.9%-102.8%. The advantage of the method is the simultaneous determination of acidic, neutral and basic compounds. It also can improve the column efficiency of the analyte, compress the half-peak width and reduce the trailing. The optimized and validated method can be used for the simultaneous determination of the five cold medicine ingredients in the tablets.

  7. Cartap hydrochloride poisoning: A clinical experience

    Directory of Open Access Journals (Sweden)

    Hari K Boorugu

    2012-01-01

    Full Text Available Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [ 3 H]-ryanodine binding to the Ca 2+ release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca 2+ influx and induction of internal Ca 2+ release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

  8. 21 CFR 556.350 - Levamisole hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride. 556.350 Section 556.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs...

  9. Cartap hydrochloride poisoning: A clinical experience.

    Science.gov (United States)

    Boorugu, Hari K; Chrispal, Anugrah

    2012-01-01

    Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [(3)H]-ryanodine binding to the Ca(2+) release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca(2+) influx and induction of internal Ca(2+) release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

  10. 21 CFR 184.1676 - Pyridoxine hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... hydrochloride that is prepared by chemical synthesis. (b) The ingredient meets the specifications of the Food... chapter; meat products as defined in § 170.3(n)(29) of this chapter; milk products as defined in § 170.3(n)(31) of this chapter; plant protein products as defined in § 170.3(n)(33) of this chapter; and...

  11. Spectrophotometric and HPLC methods for simultaneous estimation of pseudoephedrine hydrochloride and loratadine from tablets

    Directory of Open Access Journals (Sweden)

    Singhvi I

    2006-01-01

    Full Text Available Two simple, accurate, economical and reproducible UV spectrophotometric and one HPLC method for simultaneous estimation of two-component drug mixture of pseudoephedrine hydrochloride and loratadine in combined tablet dosage form have been developed. The first developed method employs multiwavelength spectroscopy using seven mixed standards and 257.0 nm and 283.0 nm as two wavelengths for estimation. The second method involves first derivative spectroscopy using 308.6 nm and 263.0 nm as zero crossing points for pseudoephedrine hydrochloride and loratadine respectively. For both spectrophotometric methods, 0.2 M hydrochloric acid was used as solvent. Linearity was observed in concentration range of 0-40 mg/ml of loratadine and 0-800 mg/ml of pseudoephedrine hydrochloride. Developed HPLC method is reverse-phase chromatographic method using Inertsil C 18 column and methanol:ammonium acetate buffer in ratio of 80:20 pH 7.5 as mobile phase. Nimesulide was used as internal standard for HPLC method. For HPLC method, linearity was observed in concentration range of 0-200 mg/ml of loratadine and 100-2000 mg/ml of pseudoephedrine hydrochloride. Results of analysis were validated statistically and by recovery studies.

  12. HPLC Determination of Propranolol Hydrochloride,Verapamil Hydrochloride and Propafenone Hydrochloride Ilegally Mixed into Wenxin Granules%高效液相色谱法测定稳心颗粒中非法添加药物的含量

    Institute of Scientific and Technical Information of China (English)

    张士勇; 程军; 叶云

    2012-01-01

    Objective To set up a method for the determination of propranolole hydrochloride, verapamil hydrochloride and propafenone hydrochloride illegally mixed into Wenxin Granules by HPLC. Methods The HPLC method was used. The Inertsil ODS - SP C18 column (250 mm × 4. 6 mm, 5 μm) was used with the mobile phase of phosphate buffer (adding water to dissolve potassium dihydrogen phosphate 6. 8 g and sodium 1 - octanesulfonate 1. 3 g, and diluting to 1 000 mL, adjusting pH value to 3.0 with phosphoric acid ) -methanol(40: 60). The flow rate was 0.8 mL/min, the detection wavelength was set at 223 nm and the column temperature was 25 ℃. Results The calibration curve showed the good linearity for propranolole hydrochloride, verapamil hydrochloride and propafenone hydrochloride in the range of 00. 019 76-2.47 μg( r = 1) ,0. 01-2. 5 μg(r = l) and 0.009 948-2.487 μg( r = 1) respectively;the average recovery rates (n = 6) were 97. 11% , 97. 63% and 98. 88% , respectively; RSD were 1. 85% , 1. 92% and 1. 46% , respectively. Conclusion This method is accurate and reproducible, which can be used for the determination of propranolole hydrochloride, verapamil hydrochloride and propafenone hydrochloride illegally mixed into Wenxin Granules.%目的 建立检测稳心颗粒中非法添加的盐酸普萘洛尔、盐酸维拉帕米和盐酸普罗帕酮含量的高效液相色谱法.方法 采用lnertsil ODS-SP C18色谱柱(250 mm×4.6 mm,5μm),流动相为磷酸盐缓冲液(取磷酸二氢钾6.8 g,辛烷磺酸钠1.3 g,加水溶解并稀释至1 000 mL,用磷酸调节pH至3.0)-甲醇(40:60),流速为0.8 mL/min,检测波长为223 nm,柱温为25℃.结果 盐酸普萘洛尔、盐酸维拉帕米和盐酸普罗帕酮进样量的线性范围分别为0.019 76~2.47 μg(r=1),0.01~2.5μg(r=1)和0.009 948~2.487μg(r=1);平均回收率分别为97.11%,97.63%和98.88%,RSD分别为1.85%,1.92%和1.46%(n=6).结论 该方法准确、重现性好,可作为稳心颗粒中非法添加盐酸普萘洛尔、

  13. Neurotrophic Effect of Asiatic acid, a Triterpene of Centella asiatica Against Chronic 1-Methyl 4-Phenyl 1, 2, 3, 6-Tetrahydropyridine Hydrochloride/Probenecid Mouse Model of Parkinson's disease: The Role of MAPK, PI3K-Akt-GSK3β and mTOR Signalling Pathways.

    Science.gov (United States)

    Nataraj, Jagatheesan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed

    2017-02-08

    Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson's disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD. AA treatment for 5 weeks significantly attenuated MPTP/p induced motor abnormalities, dopamine depletion and diminished expressions NTFs and tyrosine kinase receptors (TrKB). We further, revealed that AA treatment significantly inhibited the MPTP/p-induced phosphorylation of MAPK/P38 related proteins such as JNK and ERK. Moreover, AA treatment increased the phosphorylation of PI3K, Akt, GSK-3β and mTOR, suggesting that AA activated PI3K/Akt/mTOR signalling pathway, which might be the cause of neuroprotection offered by AA. The present findings provided more elaborate in vivo evidences to support the neuroprotective effect of AA on dopaminergic neurons of chronic Parkinson's disease mouse model and the potential of AA to be developed as a possible new therapeutic target to treat PD.

  14. Investigation of olopatadine hydrochloride under stress conditions by hydrophilic interaction liquid chromatography

    Directory of Open Access Journals (Sweden)

    Maksić Jelena Đ.

    2016-01-01

    Full Text Available The purpose of the present research was to conduct stress degradation studies on the olopatadine hydrochloride, an antiallergic drug, using the hydrophilic interaction liquid chromatography (HILIC. HILIC requires the utilization of polar and moderately polar stationary phases and aqueous-organic mobile phase usually containing more than 70% of organic solvent. In this study, olopatadine hydrochloride was subjected to acid and base hydrolysis, oxidation and termolytic degradation in order to estimate its stability under different stress conditions recommended by ICHQ1A (R2 guideline. Degree of degradation was followed by HILIC method. The chromatographic conditions were: column Betasil Cyano (100 mm × 4.6 mm, 5 mm particle size, mobile phase consisted of acetonitrile and ammonium acetate 5 mM (pH adjusted to 4.50 in ratio 85:15 V/V, flow rate was 1 mL min-1, column temperature was set at 30°C and detection was performed at 257 nm. Results obtained for stress studies indicated that olopatadine hydrochloride underwent transformation under acidic and oxidative (30% w/v hydrogen peroxyde conditions showing high degree of degradation. Furthermore, it was found that olopatadine hydrochloride is relatively stable when exposed to thermal (60°C and basic (1 M NaOH conditions. Therewith, kinetics of degradation reaction was determined with an aim to define the corresponding reaction rate constants and half-lives. Firstly, the order of the reaction was evaluated experimentally using the integral method. Based on the calculated values of the correlation coefficients, it was shown that the acidic, basic and oxidative degradation are the second-order reaction. High stability under basic conditions was achieved on the basis of the great degradation half-life values. Also, it has been verified that acidic degradation is the fastest reaction. [Projekat Ministarstva nauke Republike Srbije, br. 172052

  15. Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.

    Science.gov (United States)

    Goldeman, Waldemar; Nasulewicz-Goldeman, Anna

    2014-08-01

    A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

  16. Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

    Science.gov (United States)

    Xie, Feifan; Cheng, Zeneng; Li, Sanwang; Liu, Xingling; Guo, Xin; Yu, Peng; Gu, Zhenkun

    2014-06-01

    Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride.

  17. Stability-Indicating TLC-densitometric determination of nebivolol hydrochloride in bulk and pharmaceutical dosage form.

    Science.gov (United States)

    Shirkhedkar, Atul A; Bugdane, Prasad M; Surana, Sanjay J

    2010-02-01

    A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for densitometric determination of nebivolol hydrochloride both as a bulk drug and in formulation was developed and validated as per the international conference on harmonization guidelines (ICH). The method employed TLC aluminium plates precoated with silica gel 60F254 as the stationary phase. The solvent system consisted of toluene-methanol-triethylamine (3.8:1.2:0.2 v/v/v). Densitometry analysis of nebivolol hydrochloride was carried out in the absorbance mode at 281 nm. The system was found to give compact spot for nebivolol hydrochloride (R(f) value of 0.33 +/- 0.02). The linear regression analysis data for the calibration plots showed good relationship with r(2)= 0.9994 +/- 0.0002 in the concentration range 500-3000 ng/spot. The mean value +/- SD of slope and intercept were 3.761 +/- 0.017 and 127.39 +/- 19.53 with respect to peak area. The limits of detection (LOD) and limit of quantitation (LOQ) were 63.10 ng/spot and 191.23 ng/ spot, respectively. Nebivolol hydrochloride was subjected to acid and alkali hydrolysis, oxidation, thermal degradation, and photodegradation. All the peaks of degradation products were well-resolved from the standard drug with significantly different R(f) values. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of nebivolol hydrochloride in the bulk and pharmaceutical dosage form.

  18. A validated stability-indicative UPLC method for nilotinib hydrochloride for the determination of process-related and degradation impurities.

    Science.gov (United States)

    Kondra, Sudhakar Babu; Madireddy, Venkataramanna; Chilukuri, Mohanareddy; Papadasu, Narayanareddy; Jonnalagadda, Latha

    2014-09-01

    A novel stability-indicating ultra performance liquid chromatographic (UPLC) method has been developed for quantitative determination of nilotinib hydrochloride in active pharmaceutical ingredients along with four impurities (imp-1, imp-2, imp-3 and imp-4). The method is applicable to the quantification of related compounds and assay of nilotinib hydrochloride drug. Efficient chromatographic separation was achieved on a Shim-pack XR-ODS II, 75 × 3.0 mm, 1.8-µm column with a gradient mobile phase combination. Quantification was carried at 260 nm at a flow rate of 0.6 mL min(-1). Stress degradation conditions were established for nilotinib hydrochloride by subjecting it to acid, base, oxidation, humidity, thermal and photolysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 97.0%. The developed UPLC method was validated according to the present International Conference on Harmonisation guidelines for specificity, detection limit, quantitation limit, linearity, accuracy, precision, intermediate precision and robustness. The resolution between nilotinib hydrochloride and four potential impurities is found to be >2.0. Regression analysis shows as r value (correlation coefficient) of >0.999 for nilotinib hydrochloride and four potential impurities.

  19. Direct, preparative enantioselective chromatography of propranolol hydrochloride and thioridazine hydrochloride using carbon dioxide-based mobile phases.

    Science.gov (United States)

    Geiser, F; Schultz, M; Betz, L; Shaimi, M; Lee, J; Champion, W

    1999-12-31

    In this paper, we describe the direct, preparative enantioselective chromatography of racemic (rac)-propranolol hydrochloride (HCI) and rac-thioridazine.HCl using Chiralpak AD chiral stationary phase and mobile phase systems containing carbon dioxide and methanol without the use of basic or acidic additives. Isolated fractions of propranolol.HCl were positively identified by mass spectrometry, Beilstein flame test, melting point, and chemical analysis to be HCI enantiomers of propranolol-HCl salts exhibited characteristic mass spectra peaks at 36 and 38 mass-to-charge ratio in the expected 3:1 isotopic ratio for the solute that were absent in the mass spectra for the free-base forms. To our knowledge, the direct, preparative enantioselective isolation of HCI enantiomeric salts of rac-propranolol and of rac-thioridazine have not been previously demonstrated and published.

  20. Spectrophotometric Method for Estimation of Tamsulosin Hydrochloride in Pharmaceutical Dosage Form Using Bromate-Bromide and Methyl Orange Reagent

    Directory of Open Access Journals (Sweden)

    Bharatkumar Ganeshbhai Chaudhari

    2012-09-01

    Full Text Available A simple, rapid, accurate and precise assay procedure based on Spectrophotometric method has been developed for the estimation of Tamsulosin hydrochloride in Pharmaceutical formulation. The method was based on the bromination of Tamsulosin hydrochloride with a known excess amount of Bromate-bromide mixture in acidic medium followed by the determination of surplus bromine by reacting with dye methyl orange and measuring the absorbance at 513 nm. Validation was carried out in compliance with International Conference on Harmonization guidelines. Linear regression analysis of method showed good linearity with the correlation co-efficient (r of 0.9978 with respect to absorbance in the concentration range of 2-12 μg/mL and the mean recovery for Tamsulosin hydrochloride was 99.65% ± 0.47 . The proposed method can be successfully applied for the analysis of tablet formulations.

  1. Systemic but no local effects of combined zoledronate and parathyroid hormone treatment in experimental autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Kresten Krarup Keller

    Full Text Available INTRODUCTION: Local bone erosions and osteoporosis in rheumatoid arthritis (RA are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN and osteoblast stimulation with parathyroid hormone (PTH. METHODS: Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. RESULTS: Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. CONCLUSIONS: No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.

  2. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.

    Science.gov (United States)

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  3. [Antiseptics on the base of Octenidine Hydrochloride].

    Science.gov (United States)

    Malinovskií, N N; Reshetnikov, E A; Rubashnaia, I E; Mal'nikova, G N; Mitiukov, A P

    1997-01-01

    Comparative evaluation of laboratory and clinical investigation of antiseptic preparations on the base of octenidin-hydrochloride and bigluconate chlorhexidine in 537 patients was carried out. Statistically valid decrease in dissemination through the operation field and surgical wound after application of octenidin containing solutions was determined. It was established as well that these preparations were more effective fools of protection of the operation wound from its microbial contamination in comparison with antiseptic solutions widely spread to date in surgical practice.

  4. 抗抑郁药Duloxetine Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    艾建国; 晋展

    2003-01-01

    @@ 日本Shionogi公司获得了Eli Lilly公司的授权,对其研制的一种对5-羟色胺(5-HT)和去甲肾上腺素(NE)的摄取有双重抑制作用的化合物Duloxetine Hydrochloride (Cymbalta(R),LY-264453,LY-248686)进行了进一步的开发.

  5. Effect of iptakalim hydrochloride on hemodynamics

    Institute of Scientific and Technical Information of China (English)

    Qing-leiZHU; HaiWANG; Wen-binXIAO

    2004-01-01

    AIM: To study the effect of iptakalim hydrochloride (Ipt) on hemodynamics. METHODS: Effect of Ipt on hemodynamics were studied in anesthetized nomotensive dogs, conscious nomotensive rats (NTR), and stroke prone spontaneously hypertensive rats (SHRsp), respectively. RESULTS: In pentobarbital anesthetized nomotensive dogs, Ipt at doses of 0.125, 0.25, 0.5,1.0, and 2.0 mg/kg iv could dose-dependently decrease blood pressure (BP), with the decrease of systolic BP equivalent

  6. Cartap hydrochloride poisoning: a case report

    OpenAIRE

    Sumesh Raj; Sheetal S.

    2014-01-01

    Cartap hydrochloride is a thiocarbamate insecticide used for control of chewing and sucking insects of all stages of development, on many crops. It is an analogue of nereistoxin. Poisoning with cartap is very rarely reported from India. We report a 46 year old man who consumed cartap with alcohol, presented with nausea & vomiting and improved with supportive measures. [Int J Res Med Sci 2014; 2(1.000): 360-361

  7. Gastroretentive drug delivery system of ranitidine hydrochloride: formulation and in vitro evaluation.

    Science.gov (United States)

    Dave, Brijesh S; Amin, Avani F; Patel, Madhabhai M

    2004-04-08

    The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 3(2) full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2 = 75) among all the batches, and this similarity is also reflected in t50 (approximately 214 minutes) and t80 (approximately 537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile.

  8. Stability of paclitaxel with ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site administration.

    Science.gov (United States)

    Burm, J P; Jhee, S S; Chin, A; Moon, Y S; Jeong, E; Nii, L; Fox, J L; Gill, M A

    1994-05-01

    The stability of paclitaxel with either ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site injection at room temperature was studied. Triplicate test solutions of paclitaxel 0.3 and 1.2 mg/mL were admixed 1:1 with ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) or ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). Also, paclitaxel 1.2 mg/mL was admixed 1:1:1 with ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL. The solutions were stored in glass containers at room temperature, and samples were removed at zero, one, two, and four hours for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, and precipitation, and the pH was determined. Drug concentrations were measured by stability-indicating high-performance liquid chromatographic procedures. Throughout the study, more than 90% of the initial concentrations of paclitaxel, ondansetron, and ranitidine remained in the solutions. No precipitates, color changes, or haziness was seen. The changes in pH were minor. Paclitaxel in concentrations of 0.3 and 1.2 mg/mL was stable when mixed with either ondansetron (0.03 or 0.3 mg/mL, as the hydrochloride salt) or ranitidine (0.5 or 2.0 mg/mL, as the hydrochloride salt) and stored in glass containers for four hours. Paclitaxel 1.2 mg/mL was also stable when mixed with both ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL and stored in glass containers for four hours.

  9. Simultaneous determination of pseudoephedrine hydrochloride and cetrizine hydrochloride by reverse phase high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Nalini C

    2006-01-01

    Full Text Available A reversed phase high performance liquid chromatographic method has been developed using Shimadzu HPLC-VP series, LC-10 ATV pump, SPD10 AVP and C8 column, for simultaneous determination of pseudoephedrine hydrochloride and cetrizine hydrochloride in three marketed tablet formulations (extended release. The mobile phase consists of phosphate buffer of pH 7.0 and acetonitrile HPLC grade in the ratio of 1:1. The flow rate was maintained at 1 ml/min and the ultraviolet detection was done at 242 nm, which is the isosbestic point. Linearity coefficients, assay values, recovery studies and repeatability studies showed that the method is accurate and precise.

  10. Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method.

    Science.gov (United States)

    Malleswararao, Chellu S N; Suryanarayana, Mulukutla V; Mukkanti, Khagga

    2012-01-01

    A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.7 μm, column using a buffer consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL min(-1) and the detection wavelength was 210 nm. The limit of detection (LOD) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06 μg mL(-1), respectively. The limit of quantification (LOQ) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 μg mL(-1), respectively. This method was validated with respect to linearity, accuracy, precision, specificity and robustness. The method was also found to be stability-indicating.

  11. DEVELOPMENT AND VALIDATION OF STABILITY-INDICATING TLC-DENSITOMETRY METHOD FOR THE SIMULTANEOUS DETERMINATION OF EPERISONE HYDROCHLORIDE AND PARACETAMOL IN BULK AND TABLET DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Pritam S. Jain

    2013-08-01

    Full Text Available A rapid and reproducible stability indicating TLC-densitometric method was developed for the determination of eperisone hydrochloride and paracetamol in presence of their degraded products in bulk drugs and pharmaceutical formulations. Uniform degradation conditions were maintained by refluxing reaction mixtures for 8 h at 60°C including acidic, alkaline hydrolysis. Oxidation at room temperature, photochemical and dry heating degradation studies were also carried out. A sensitive and robust stability indicating TLC-densitometric method for simultaneous quantification of eperisone hydrochloride and paracetamol in bulk drugs and pharmaceutical formulations has been developed and validated. Separation was done on TLC aluminum sheets, pre-coated with silica gel 60F-254 using ethyl acetate: toluene: methanol (2:2:1 v/v/v. Spots at Rf 0.42 ± 0.04 and Rf 0.60 ± 0.02 were recognized as paracetamol and eperisone hydrochloride, respectively. Densitometric analysis of chromatoplates was carried out in absorbance mode at isobastic point 260 nm. The developed method was optimized and validated as per ICH guidelines. Method was found linear over the concentration range of 100-350 ng / spot for eperisone hydrochloride and 600-2100 ng / spot for paracetamol with the correlation coefficient (r2 of 0.999 and 0.999 for eperisone hydrochloride and paracetamol, respectively. The developed TLC method can be applied for routine analysis of eperisone hydrochloride and paracetamol in presence of their degraded products in their combined pharmaceutical formulations.

  12. Fenton degradation of Cartap hydrochloride: identification of the main intermediates and the degradation pathway.

    Science.gov (United States)

    Tian, Kaixun; Ming, Cuixiang; Dai, Youzhi; Honore Ake, Kouassi Marius

    2015-01-01

    The advanced oxidation of Cartap hydrochloride (Cartap) promoted by the Fenton system in an aqueous medium was investigated. Based on total organic carbon, chemical oxygen demand and high-performance liquid chromatography, the oxidation of Cartap is quite efficient by the Fenton system. Its long chain is easily destroyed, but the reaction does not proceed to complete mineralization. Ion chromatography detection indicated the formation of acetic acid, propionic acid, formic acid, nitrous acid and sulfuric acid in the reaction mixtures. Further evidence of nitrogen monoxide and sulfur dioxide formation was obtained by using a flue gas analyzer. Monitoring by gas chromatograph-mass spectrometer demonstrated the formation of oxalic acid, ethanol, carbon dioxide, and L-alanine ethylamide. Based on these experimental results, plausible degradation pathways for Cartap mineralization in an aqueous medium by the Fenton system are proposed.

  13. Stability-Indicating RP-HPLC Method for Determination of Guanfacine Hydrochloride in Bulk Drugs and in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    Vinod K. Ahirrao

    2011-04-01

    Full Text Available A novel stability-indicating RP-HPLC method was developed and validated for quantitative determination of guanfacine hydrochloride in bulk drug and in pharmaceutical dosage form. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using Apollo, C18 (250mm x 4.6mm, 5µm column with mobile phase of 50mM Ammonium acetate (volatile buffer and acetonitrile (65:35, v/v. UV detection has been done at wavelength 220 nm. The guanfacine hydrochloride was subjected to the stress conditions of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. The stressed samples were analyzed by the proposed method. The analyte peak shape was excellent. The described method shows excellent linearity over a range of 30 – 450 µg/mL. The correlation coefficient for guanfacine hydrochloride was 0.999. The limit of detection for Guanfacine hydrochloride is 0.011 µg/mL and the limit of quantification is 0.038 µg/mL respectively.Degradation was observed for guanfacine hydrochloride in base, thermal and in 30% H2O2 conditions. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from main peak. The percentage recovery of guanfacine hydrochloride was ranged from (99.2% to 100.5% in pharmaceutical dosage form. The developed method was validated with respect to the linearity, accuracy (recovery, precision, specificity and robustness. The forced degradation studies prove the stability indicating power of the method.

  14. 21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b Section 520.1660b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule...

  15. 21 CFR 520.2345a - Tetracycline hydrochloride capsules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline hydrochloride capsules. 520.2345a... Tetracycline hydrochloride capsules. (a) Specifications. Each capsule contains 50, 100, 125, 250, or 500... as in paragraph (c) of this section: (1) No. 000009: 250 mg per capsule. (2) No. 000069: 125, 250, or...

  16. 21 CFR 520.1242f - Levamisole hydrochloride gel.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride gel. 520.1242f Section 520.1242f Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Levamisole hydrochloride gel. (a) Specifications. The drug is a gel containing 11.5 percent...

  17. 21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride oral dosage forms. 520.1242 Section 520.1242 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242 Levamisole hydrochloride oral dosage...

  18. 21 CFR 520.1242e - Levamisole hydrochloride effervescent tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride effervescent tablets. 520.1242e Section 520.1242e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242e Levamisole hydrochloride...

  19. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  20. Vibrational spectra of pilocarpine hydrochloride crystals

    Energy Technology Data Exchange (ETDEWEB)

    Bento, R.R.F. [Universidade Federal de Mato Grosso (UFMT), Cuiaba, MT (Brazil). Inst. de Fisica; Freire, P.T.C. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Fisica]. E-mail: tarso@fisica.ufc.br; Teixeira, A.M.R.; Silva, J.H. [Universidade Regional do Cariri, Crato, CE (Brazil). Dept. Ciencias Fisicas e Biologicas; Lima Junior, J.A. [Universidade Estadual do Ceara (UECE), Limoeiro do Norte, CE (Brazil); Oliveira, M.C.F. de; Andrade-Neto, M. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica; Romero, N.R. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Farmacia; Pontes, F.M. [Universidade Estadual Paulista, Bauru, SP (Brazil). Faculdade de Ciencias

    2009-03-15

    Pilocarpine is a natural substance with potential application in the treatment of several diseases. In this work Fourier Transform (FT)-Raman spectrum and the Fourier Transform infra red (FT-IR) spectrum of pilocarpine hydrochloride C{sub 11} H{sub 17} N{sub 2} O{sup +}{sub 2} .Cl{sup -1} were investigated at 300 K. Vibrational wavenumber and wave vector have been predicted using density functional theory (B3LYP) calculations with the 6-31 G(d,p) basis set. A comparison with experiment allowed to assign most of the normal modes of the crystal. (author)

  1. Ultraviolet spectrophotometric method for analytical determination of mianserin hydrochloride in coated tablets and comparison with LC

    Directory of Open Access Journals (Sweden)

    Letícia Lenz Sfair

    2015-12-01

    Full Text Available abstract Ultraviolet spectrophotometric (UV and Liquid Chromatographic (LC methods for the determination of mianserin hydrochloride in pharmaceutical formulation were developed and validated. The various parameters, such as specificity, linearity, precision and accuracy were studied according to International Conference on Harmonization (ICH, 2005. For UV method, mianserin hydrochloride was determinate at 278 nm using HCl 0.1 M as the solvent. The response was linear in the concentration range of 20.0 - 140.0 µg/mL (r = 0.9998. Precision data evaluated by relative standard deviation was lower than 2%. The UV method was simple, rapid and low cost. Chromatographic analyses were performed in an Ace C18 column and the mobile phase was composed of methanol, 50 mM monobasic potassium phosphate buffer and 0.3% triethylamine solution adjusted to pH 7.0 with phosphoric acid 10% (85:15. LC method was specific, linear, precise, exact and robust. The results confirmed that the both methods are valid and useful to the routine quality control of mianserin hydrochloride in coated tablets. Statistical analysis by Student´s t-test showed no significant difference between the results obtained by UV and LC methods.

  2. [Neuropharmacological studies on tolperisone hydrochloride (author's transl)].

    Science.gov (United States)

    Fujii, Y; Ishii, Y; Suzuki, T; Murayama, S

    1979-10-01

    Neuropharmacological properties of tolperisone hydrochloride (2,4'-dimethyl-3-piperidinopropiophenone hydrochloride) were investigated in mice, rats and cats. Tolperisone inhibited the spontaneous movement and methamphetamine-induced hyperactivity in mice and the ED50 was approx. 50 mg/kg, s.c. At this dose, tolperisone did not prolong the pentobarbital-induced sleeping time. Tolperisone inhibited convulsions induced by pentylenetetrazol, nicotine and maximum electric shock, but did not affect convulsions induced by strychnine and picrotoxin. Tolperisone induced muscle relaxation in mice and rats in several pharmacological tests, but did not affect neuro-muscular transmission. Tolperisone did not affect conditioned avoidance response in rats and methamphetamine-induced rotational behaviour in nigro-lesioned rats. Tolperisone reduced decerebrated rigidity in cats with i.v. administration of 5 approximately 10 mg/kg and intraduodenal administration of 50 approximately 100 mg/kg. Tolperisone elicited a slight drowsy pattern in the spontaneous EEG of cats at 5 approximately 10 mg/kg, i.v., and inhibited the EEG arousal response and pressor response to stimulation of mesencephalic reticular formation or posterior hypothalamic area. These results suggest that inhibition of the activity in the gamma pathway descending from the mesencephalic reticular formation may be involved in the mechanism of muscle relaxant action of tolperisone.

  3. Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids

    Directory of Open Access Journals (Sweden)

    Czarniak P

    2016-03-01

    Full Text Available Petra Czarniak, Michael Boddy, Bruce Sunderland, Jeff D Hughes School of Pharmacy, Curtin University, Perth, WA, Australia Purpose: The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride in commonly used intravenous fluids at room temperature (25°C, at accelerated-degradation temperatures and in selected buffer solutions.Materials and methods: The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride stored at 25°C±0.1°C in sodium lactate (Hartmann’s, 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined.Results: Lincomycin hydrochloride was found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days, and was least stable at pH 2 (calculated shelf life of 0.38 days.Conclusion: Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability. Keywords: lincomycin, stability, pH, intravenous fluids, IV additives

  4. Identification of polymorphism in ethylone hydrochloride: synthesis and characterization.

    Science.gov (United States)

    Maheux, Chad R; Alarcon, Idralyn Q; Copeland, Catherine R; Cameron, T Stanley; Linden, Anthony; Grossert, J Stuart

    2016-08-01

    Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT-Raman, powder XRD, GC-MS, ESI-MS/MS and NMR ((13) C CPMAS, (1) H, (13) C). The two polymorphs can be distinguished by vibrational spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra'. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X-ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

  5. Effect of aminolevulinic acid hydrochloride on the acne model of rabbits' ears%盐酸氨基乙酰丙酸搽剂对实验性兔耳痤疮的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张成梅; 武传涛; 尹志圣; 李春令; 于学慧; 王立; 刘兆平

    2011-01-01

    Objective To investigate the therapeutic effect of aminolevulinic acid (ALA) linimentum on exprimental acne of New Zealand rabbits' ears. Methods Thirty-two healthy adult New Zealand rabbits were used in this experiment. Propionibacterium acnes and oleic acid were administrated to the right inner ears (2 cm× 2 cm range) of the rabbits to establish acne models. Then all the animals were randomly divided into 5 groups, ① the model control group:photodynamics therapy(PDT) was given after solvent was applied in the disease region, once per week for 3 weeks, ②the clindamycin metronidazole acne positive control group: clindamycin metronidazole was smeared in the disease region, 3 times/d for 2 weeks, ③ the retinoid positive control group: retinoid was applied in the disease region, 3 times/d for 2 weeks, ④ the ALA single treatment group: ALA was applied in the disease region, once in the first week, ⑤the ALA repeated treatment group: ALA was applied in the disease region, once per week for 3 weeks, and ⑥the normal control group. The animals in the ALA treatment groups and model control group were protected from light for 3 hours after administration, and then ALA photodynamic therapy(ALA-PDT) was given for 15 min/time. After treatment biopsy, and HE staining, microscopic and histological examination were carried out. Results Statistical resuits and biopsy showed that there was a good therapeutic effect on the rabbits' acne models caused by propionibacterium acnes / oleic acid in the ALA-PDT treatment group ( P <0.01 or P <0.05). The effect in the other two positive treatment groups was also obvious ( P < 0.05 ), and the therapeutic effect in the ALA-PDT repeated treatment group was stronger than in the ALA-PDT single treatment group and the two positive drug groups. Conclusion Repeated ALAPDT treatment has good therapeutic effect on rabbits' acne models caused by pwpionibacterium acnes/oleic acid.%目的 研究盐酸氨基乙酰丙酸(ALA)搽剂对新

  6. SIMULTANEOUS ESTIMATION AND VALIDATION OF VARDENAFIL AND DAPOXETINE HYDROCHLORIDE IN PHARMACEUTICAL FORMULATION BY THIN LAYER CHROMATOGRAPHIC DENSITOMETRIC METHOD

    Directory of Open Access Journals (Sweden)

    Bhavin Chapla

    2012-05-01

    Full Text Available The present manuscript describes new, simple, accurate, and precise high performance thin layer chromatography method for the simultaneous determination of Vardenafil and Dapoxetine in combined tablet dosage form. Chromatographic separation of the drugs was performed on aluminium plates pre coated with silica gel 60 F254 as the stationary phase and the solvent system consisted of Chloroform: Methanol: Acetonitrile: Formic acid (4: 0.8: 4: 1 v/v/v/v. Densitometric evaluation of the separated zones was performed at 232 nm. The two drugs were satisfactorily resolved with Rf values 0.47 and 0.79 for Vardenafil and Dapoxetine Hydrochloride, respectively. The linear regression data for the calibration plots showed good relationship with r2 = 0.9995 from 150-750 ng/spot for Vardenafil and r2 = 0.9980 from 450-2250 ng/spot for Dapoxetine Hydrochloride. The methods were validated for precision, accuracy, and recovery. The percentage recovery for Vardenafil was found to be 99.58 – 100.72 % and 99.97 – 100.21% for Dapoxetine Hydrochloride. The limits of detection and quantification were 21.86 and 66.25 ng/spot per spot for Vardenafil and 128.58. and 389.64 ng/spot per spot for Dapoxetine Hydrochloride, respectively.

  7. Capillary electrophoresis coupled with electrochemiluminescence for determination of cloperastine hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To investigate the electrochemiluminescence (ECL) behavior of cloperastine hydrochloride. Methods ECL intensity of tris (2,2′-bipyridyl) rutheniumo(Ⅱ) was enhanced, the method for the determination of cloperastine hydrochloride was established using capillary electrophoresis (CE) coupled with electrochemilumolinescence (ECL) detection. Results Under the optimum conditions, ECL intensity varied linearly with cloperastine hydrochloride concentration from 7.0×10-6g/mL to 1.0×10-4g/mL. The detection l...

  8. COMPARISON OF DROTAVERINE HYDROCHLORIDE AND VALETHAMATE BROMIDE ON CERVICAL DILATATION

    Directory of Open Access Journals (Sweden)

    Mallika Selvaraj

    2016-06-01

    Full Text Available AIM To compare the two drugs drotaverine hydrochloride and valethamate bromide and their effects on cervical dilatation and labour duration. METHODOLOGY It is a prospective study undertaken at Government Rajaji Hospital on 150 randomly selected primigravidae patients. RESULTS The duration of active phase of first stage of labour was significantly reduced (p value 0.003, rate of cervical dilatation was higher (p value 0.0001 with drotaverine hydrochloride. CONCLUSION Drotaverine hydrochloride is a safe, potent and effective drug to be used in the active phase of labour.

  9. Magnetic resonance imaging study of the transport phenomena of solvent into the gel layer of hypromellose matrices containing tetracycline hydrochloride.

    Science.gov (United States)

    Tritt-Goc, Jadwiga; Kowalczuk, Joanna; Pislewski, Narcyz

    2003-11-01

    Magnetic resonance imaging was used to study the diffusion of a water solution of hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices. Spatially resolved information was obtained about the self-diffusion coefficient and spin-spin relaxation time of solvent protons in the gel layer of hypromellose matrices loaded with different amounts of tetracycline hydrochloride. The data showed the influence of the drug concentration on the diffusion and spin-spin relaxation. Higher drug concentrations in the hypromellose matrix led to greater swelling of the matrix and faster diffusion of the water molecules inside the gel layer of the polymer. The observed differences between the radial and axial diffusion were interpreted in terms of the stresses imposed in the axial direction during the compression of the samples. The spin-spin and diffusion profiles indicated that the diffusion of a water solution of hydrochloric acid into hypromellose, pure and loaded with different amounts of tetracycline hydrochloride, was characterized as a Case II mechanism.

  10. 度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛的疗效观察%Therapeutic effect analysis of duloxetine hydrochloride combined with alpha-lipoic acid in treatment of diabetic peripheral neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    沈柿芬; 郭道骝

    2016-01-01

    目的:探讨度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛的有效性及安全性。方法:将78例糖尿病周围神经病变性疼痛患者随机分为两组,西汀组口服度洛西汀,联合组口服度洛西汀和静脉滴注硫辛酸,比较两组疗效。结果:两组治疗后正中神经感觉传导速度(median nerve conduction velocity,MNCV)、腓总神经感觉传导速度(phil nerve conduction velocity,PNCV)、尺神经感觉传导速度(ulnar nerve conduction velocity,UNCV)均显著提高(P0.05);两组治疗前、治疗8周后胆固醇(TC)、甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、血肌酐(SCr)指标水平均无显著性变化(P>0.05)。结论:度洛西汀联合硫辛酸治疗糖尿病周围神经病变性疼痛,能有效改善患者神经功能,减轻疼痛症状,且安全可靠。%Objective:By comparing duloxetine combination with alpha-lipoic acid and duloxetine in the therapeutic effect of painful diabetic neuropathy, to explore the efficacy and safety of duloxetine combination with alpha-lipoic acid treatment on diabetic peripheral neuropathic pain (DPNP) is optimal.Methods:78 cases with painful diabetic neuropathy of type 2 diabetes were recruited from our department and randomly divided into two groups, which were duloxetine in combination with alpha-lipoic acid group and duloxetine treatment group.Results: Compared to baseline, median nerve sensory conduction velocity (MNCV), Phil nerve conduction velocity (PNCV) and ulnar nerve conduction velocity (UNCV) of both groups were better (P0.05). Before treatment, no statistically signiifcant differences were detected in total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (SCr) between two groups (P>0.05).Conclusion:Duloxetine hydrochloride combined with alpha-lipoic acid has a good

  11. 盐酸吡哆辛在石墨烯-碳纳米管/聚烟酸复合修饰电极上的电化学行为研究及其测定%Electrochemical Behavior and Determination of Pyridoxine Hydrochloride at Graphene-Carbon Nanotubes/Poly(nicotinic acid) Modified Electrode

    Institute of Scientific and Technical Information of China (English)

    何凤云; 俞静; 刘欢; 顾小燕; 唐鹏鹏; 周宏; 陈昌云; 陆国飞

    2014-01-01

    Graphene ( GN) and multiwalled carbon nanotubes ( MWCNT) composites were coated on glassy carbon electrode ( GCE ) and then poly ( nicotinic acid ) ( PNA ) was electrodeposited on the modified electrode. The electrochemical behavior of pyridoxine hydrochloride ( VB6 ) was investigated at the modified electrode by cyclic voltammetry ( CV ) and differential pulse voltammetry ( DPV ) . Results showed the oxidation current of VB6 at the GN-MWCNT/PNA/GCE was obviously larger than that at GCE, PNA/GCE and GN/MWCNT/GCE. The oxidation process of VB6 was an irreversible diffusion-controlled process involving one electron and two protons. The liner range between the peak current intensity of DPV and the concentration of VB6 was 0 . 05-200 μmol/L with a detection limit of 0 . 02 μmol/L ( S/N=3 ) . The modified electrode showed a good reproducibility with a relative standard deviation of 3 . 1% ( n=8 ) . The proposed method was applied to the analysis of vitamin B6 in vitamin B6 tablets and compound vitamin B tablets with recoveries between 96 . 1%-104 . 5%.%通过滴涂和电聚合的方法制备了石墨烯( GN)-多壁碳纳米管( MWCNTs)/聚烟酸( PNA)修饰玻碳电极。利用循环伏安法和差分脉冲伏安法考察了盐酸吡哆辛( VB6)在此修饰电极上的电化学行为和测定方法。结果表明,VB6在此修饰电极上有一明显的不可逆氧化峰(Epa=1.049 V),该电极与 GCE、PNA/GCE以及GN/MWCNT/GCE相比,VB6的氧化峰电流显著提高,电极反应为扩散控制的一电子两质子反应。利用差分脉冲伏安法对VB6进行测定,线性范围为0.05~200μmol/L,检出限为0.02μmol/L,相对平均偏差为3.1%(n=8)。本方法可用于测定VB6片和B族维生素片中的VB6含量测定,加标回收率为在96.1%~104.5%之间。

  12. Dyeing Characteristics of Chitosan Biguanidine Hydrochloride Treated Wool Fabrics

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Chitosan biguanidine hydrochloride(CGH) has been synthesized by the guanidineylation reaction of chitosan with dicyandiamide.The structures of CGH were characterized by Fourier transform infrared spectroscopy and 13CNMR spectra.In this paper,we used citric acid(CA) as a crosslinking agent,mixed with CGH to perform a pad-drycure treatment on wool fabric to study reaction mechanism during crosslinking with the help of Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM).Dyeing characteristics of CGH treated wool fabric was assessed.The effects of CGH concentration,curing temperature,dipping time,pH value on color yield of reactive dyes on wool fibres were investigated.Fastness properties of the modified wool fabric to laundering and crocking have also been discussed.Fourier transform infrared spectroscopy(FT-IR) showed that CA produce esterification with the-OH group of the wool and transamidation with the-NH2 group of the CGH to form a crosslink.Scanning electron microscopy(SEM) analysis showed the CGH firmly attached to the surface of wool fibre.It was found that the CGH pretreated wool fabrics had significantly improved dyeability characteristics.It is worthwhile to mention that the CGH treated samples have antibacterial potential due to the antibacterial property of chitosan molecules and guanidinium salts.

  13. DESIGN OF GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF DILTIAZEM HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    L. K. Omray

    2014-02-01

    Full Text Available Gastro retentive drug delivery system of diltiazem hydrochloride was designed and evaluated for its effectiveness for the management of mild to moderate hypertension. Gastro retentive drug delivery system were prepared using polyvinyl alcohol and sodium carboxy methyl cellulose as the polymers and sodium bicarbonate as a gas generating agent for the reduction of floating lag time. Gastro retentive drug delivery system tablets were prepared by wet granulation method by compression in tablet compression machine. Formulations DL1, DL2, DL3, DL4 and DL5 were developed which differed in the ratio of polyvinyl alcohol and sodium carboxy methyl cellulose polymers. All the formulations were evaluated for hardness, weight variation, friability, drug content, swelling index, buoyancy studies and in vitro drug release study. In vitro drug release study was performed using United State Pharmacopoeia 23 type 2 dissolution test apparatus employing paddle stirrer at 50 r/pm. Dissolution medium was 900 ml of 0.1N hydrochloric acid at 37ºC ± 3ºC. Formulations DL3 was found to be better as compared to other formulation.

  14. Development and evaluation of microporous osmotic tablets of diltiazem hydrochloride.

    Science.gov (United States)

    Bathool, Afifa; Gowda, D V; Khan, Mohammed S; Ahmed, Ayaz; Vasudha, S L; Rohitash, K

    2012-04-01

    Microporous osmotic tablet of diltiazem hydrochloride was developed for colon targeting. These prepared microporous osmotic pump tablet did not require laser drilling to deliver the drug to the specific site of action. The tablets were prepared by wet granulation method. The prepared tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan coating process. The incorporation of sodium lauryl sulfate (SLS), a leachable pore-forming agent, could form in situ delivery pores while coming in contact with gastrointestinal medium. The effect of formulation variables was studied by changing the amounts of sodium alginate and NaCMC in the tablet core, osmogen, and that of pore-forming agent (SLS) used in the semipermeable coating. As the amount of hydrophilic polymers increased, drug release rate prolonged. It was found that drug release was increased as the concentration of osmogen and pore-former was increased. Fourier transform infrared spectroscopy and Differential scanning calorimetry results showed that there was no interaction between drug and polymers. Scanning electron microscopic studies showed the formation of pores after predetermined time of coming in contact with dissolution medium. The formation of pores was dependent on the amount of pore former used in the semipermeable membrane. in vitro results showed acid-resistant, timed release at an almost zero order up to 24 hours. The developed osmotic tablets could be effectively used for prolonged delivery of Diltiazem HCl.

  15. Development and evaluation of microporous osmotic tablets of diltiazem hydrochloride

    Directory of Open Access Journals (Sweden)

    Afifa Bathool

    2012-01-01

    Full Text Available Microporous osmotic tablet of diltiazem hydrochloride was developed for colon targeting. These prepared microporous osmotic pump tablet did not require laser drilling to deliver the drug to the specific site of action. The tablets were prepared by wet granulation method. The prepared tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan coating process. The incorporation of sodium lauryl sulfate (SLS, a leachable pore-forming agent, could form in situ delivery pores while coming in contact with gastrointestinal medium. The effect of formulation variables was studied by changing the amounts of sodium alginate and NaCMC in the tablet core, osmogen, and that of pore-forming agent (SLS used in the semipermeable coating. As the amount of hydrophilic polymers increased, drug release rate prolonged. It was found that drug release was increased as the concentration of osmogen and pore-former was increased. Fourier transform infrared spectroscopy and Differential scanning calorimetry results showed that there was no interaction between drug and polymers. Scanning electron microscopic studies showed the formation of pores after predetermined time of coming in contact with dissolution medium. The formation of pores was dependent on the amount of pore former used in the semipermeable membrane. in vitro results showed acid-resistant, timed release at an almost zero order up to 24 hours. The developed osmotic tablets could be effectively used for prolonged delivery of Diltiazem HCl.

  16. Spectrophotometric methods for the determination of ritodrine hydrochloride and its application to pharmaceutical preparations.

    Science.gov (United States)

    Revanasiddappa, H D; Manju, B

    2001-08-01

    Two simple and sensitive spectrophotometric methods are described for the determination of ritodrine hydrochloride (RTH) in both pure and dosage forms. The methods are based on the interaction of diazotised p-nitroaniline (DPNA) and sulphanilic acid (DSNA) with RTH in an alkaline medium. The resulting azo dyes are measured at 480 nm (for the DPNA method) and at 440 nm (for the DSNA method) and are stable for more than 1 h. The optimum reaction conditions and other analytical parameters are evaluated. A study of the effect of commonly associated excipients and additives do not interfere with the determinations. Statistical analysis of results indicates that the methods are precise and accurate.

  17. Distribution of non-tasters for phenylthiocarbamide and high sensitivity to quinine hydrochloride of the non-tasters in Japanese.

    Science.gov (United States)

    Sato, T; Okada, Y; Miyamoto, T; Fujiyama, R

    1997-10-01

    The percentage of non-tasters for phenylthiocarbamide in 915 Japanese students was 9.4%. The thresholds of the edge and back of the tongue to quinine hydrochloride were significantly smaller in the non-tasters than in the tasters. The thresholds of any tongue portions to NaCl, acetic acid or sucrose did not differ between the tasters and the non-tasters.

  18. UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

    Science.gov (United States)

    Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

    2012-10-01

    The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

  19. A novel formulation for mebeverine hydrochloride.

    Science.gov (United States)

    Abdel-Hamid, Sameh M; Abdel-Hady, Seham E; El-Shamy, Abdel-Hamid A; El-Dessouky, Hadir F

    2007-10-01

    The antispasmodic drug mebeverine hydrochloride was formulated into a film-forming gel to be used as a topical local anesthetic. A mixture of cellulose derivatives was used as a base. Additives were used to enhance the release as well as the residence time. Formulations were characterized in terms of drug release, mucoadhesion and rheology. Clinically, the selected formula has shown faster onset (p = 0.0156), longer duration (p = 0.0313), better film residence (p = 0.0313), and no foreign body sensation (p = 0.0313) in comparison to Solcoseryl dental paste. Histopathological examination showed no change in inflammatory cells count, concluding that this topical anesthetic is efficacious and safe orally.

  20. Effect of sertraline hydrochloride on dialysis hypotension.

    Science.gov (United States)

    Dheenan, S; Venkatesan, J; Grubb, B P; Henrich, W L

    1998-04-01

    Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease (ESRD) and plays a key role in HH in some patients. Sertraline hydrochloride, a central nervous system serotonin reuptake inhibitor, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction in disorders such as neurocardiogenic syncope and idiopathic orthostatic hypotension. This study sought to determine whether sertraline was effective in ameliorating HH. A retrospective chart analysis was performed that included nine consecutive patients (aged > or = 54 years, time on hemodialysis > or = 2.2 years) placed on sertraline (50 to 100 mg/d) for depression who also had HH (defined as prehemodialysis systolic blood pressure [SBP] or = 40 mm Hg decrease in SBP during hemodialysis, SBP sertraline. The data from a 6-week pre-sertraline period were compared with the data from a 6-week sertraline period (defined as 6 weeks after drug begun). Blood pressure medications were unchanged during the trial period of sertraline. However, nadir mean arterial pressure recorded during a given dialysis session in the pre-sertraline period (55+/-4 mm Hg) was significantly lower than that recorded in the sertraline period (68+/-5 mm Hg; P sertraline period was significantly lower than that during the pre-sertraline period (mean, 0.6+/-0.2 episodes per session v 1.4+/-0.3 episodes per session; P sertraline period was also significantly less than that during the pre-sertraline period (mean, 1.7+/-0.8 interventions v 11.0+/-3.0 interventions; P sertraline hydrochloride reduces HH in some patients with ESRD. A possible mechanism for this effect is sertraline-induced attenuation of the paradoxical sympathetic withdrawal that may underlie HH in some patients with ESRD.

  1. Dyeing Characteristics of Chitosan Biguanidine Hydrochloride Treated Wool Fabrics

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue; HE JIN-xin

    2010-01-01

    @@ Chitosan biguanidine hydrochloride(CGH)has been synthesized by the guanidineylation reaction of chitosan with dicyandiamide.The structures of CGH were characterized by Fourier transform infrared spectroscopy and 13CNMR spectra.

  2. Non-pigmented fixed drug eruption induced by eprazinone hydrochloride.

    Science.gov (United States)

    Tanabe, Kenichi; Tsuboi, Hiromi; Maejima, Hideki; Arai, Satoru; Katsuoka, Kensei

    2005-12-01

    A 68-year-old woman developed an upper respiratory tract infection in November 2002 and was treated with eprazinone hydrochloride, serrapeptase, carbocysteine and clarithromycin. Three days after the start of treatment, the patient noted erythema on her axilla, buttock and inguinal regions. The erythema subsided in 7 days although slight pigmentation remained. However, 7 days later the pigmentation completely disappeared. Oral eprazinone hydrochloride was given as a challenge, and 1 day later the erythema re-appeared in the same areas as on initial presentation (axilla, buttock, and inguinal regions). A fixed erythema without lasting pigmentation is attributed to eprazinone hydrochloride. Therefore, the patient was diagnosed as having a nonpigmented fixed drug eruption associated with eprazinone hydrochloride.

  3. Antifungal activity of hydrochloride salts of tylophorinidine and tylophorinine.

    Science.gov (United States)

    Dhiman, Mini; Parab, Rajashri R; Manju, Sreedharannair L; Desai, Dattatraya C; Mahajan, Girish B

    2012-09-01

    The antimicrobial efficacy of two phenanthroindolizidine alkaloids, tylophorinidine hydrochloride (TdnH) and tylophorinine hydrochloride (TnnH), isolated from the plant Tylophora indica (local name, Antamul) was evaluated. These were screened for in vitro antifungal and antibacterial activities. Both compounds exhibited potent antifungal activity displaying minimum inhibitory concentrations (MIC) in the range of 2-4 microg/mL for TdnH and 0.6-2.5 microg/mL for TnnH against Candida species.

  4. Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops

    OpenAIRE

    Eiichi Uchio

    2008-01-01

    Eiichi UchioDepartment of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanAbstract: Olopatadine hydrochloride exerts a wide range of pharmacological actions such as histamine H1 receptor antagonist action, chemical mediator suppressive action, and eosinophil infiltration suppressive action. Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol®) was introduced to the market in Japan in October 2006. In a conjunctival allergen challenge (CAC) test, olopatadine...

  5. COMPARISON OF DROTAVERINE HYDROCHLORIDE AND VALETHAMATE BROMIDE ON CERVICAL DILATATION

    OpenAIRE

    Mallika Selvaraj; Sumathi

    2016-01-01

    AIM To compare the two drugs drotaverine hydrochloride and valethamate bromide and their effects on cervical dilatation and labour duration. METHODOLOGY It is a prospective study undertaken at Government Rajaji Hospital on 150 randomly selected primigravidae patients. RESULTS The duration of active phase of first stage of labour was significantly reduced (p value 0.003), rate of cervical dilatation was higher (p value 0.0001) with drotaverine hydrochloride. CONCLUS...

  6. Simultaneous Spectrophotometric Determination of Drotaverine Hydrochloride and Paracetamol in Tablet

    OpenAIRE

    Mahaparale Sonali; Telekone R; Raut R; Damle S; Kasture P

    2010-01-01

    Two simple, accurate and reproducible spectrophotometric methods; Q analysis and first order derivative method have been described for the simultaneous estimation of drotaverine hydrochloride and paracetamol in combined tablet dosage form. Absorption maxima of drotaverine hydrochloride and paracetamol in distilled water were found to be 303.5 nm and 243.5 nm respectively. Beer′s law was obeyed in the concentration range 5-50 µg/ml for drotaverine and 5-60 µg/ml for paracetamo...

  7. Development of LC Method for the Simultaneous Determination of Antidepressant Drug Combination Melitracen Hydrochloride and Flupentixol Dihydrochloride in their Combined Dosage Form

    Directory of Open Access Journals (Sweden)

    Usmangani K. Chhalotiya

    2011-01-01

    Full Text Available A simple, specific and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of melitracen hydrochloride and flupentixol dihydrochloride in tablet dosage form. A Brownlee C-18, 5 μm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.025 M potassium dihydrogen phosphate: methanol (10 : 90, v/v; pH 7.3 was used. The flow rate was 1.0 mL/min, and effluents were monitored at 230 nm. The retention times of melitracen hydrochloride and flupentixol dihydrochloride were 7.75 min and 5.50 min, respectively. The linearity for melitracen hydrochloride and flupentixol dihydrochloride were in the range of 0.5–60 μg/mL. The recoveries obtained for melitracen hydrochloride and flupenthixol dihydrochloride was 99.81–100.77% and 99.42–100.12%, respectively. Both the drugs were subjected to acid and alkali hydrolysis, chemical oxidation, and dry heat degradation and photodegradation. The proposed method was validated and successfully applied to the estimation of melitracen hydrochloride and flupentixol dihydrochloride in combined tablet dosage form.

  8. Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Impurities in Cinacalcet Hydrochloride API and its Formulation.

    Science.gov (United States)

    Sunil Reddy, Pingili; Raju, Thummala Veera Raghava; Raju, Penmetsa Satyanarayana; Varma, Nadimpalli Sunil; Babu, Kondra Sudhakar

    2015-01-01

    A sensitive, stability-indicating, gradient reversed-phase ultra-performance liquid chromatography method has been developed for the quantitative estimation of cinacalcet hydrochloride impurities in active pharmaceutical ingredients and pharmaceutical formulations. Efficient chromatographic separation was achieved on an Acquity BEH Shield RP18, 100 × 2.1 mm, 1.7 µm column with the mobile phase containing pH 6.6 phosphate buffer and acetonitrile. The flow rate of the mobile phase was 0.3 mL min(-1) with a column temperature of 35°C and detection wavelength at 223 nm. The relative response factor values of (+)-R-1-(1-Naphthyl)ethylamine, regioisomer, diastereomer isomer-1, and diastereomer isomer-2 were 1.79, 0.99, 0.89, and 0.88, respectively. The cinacalcet hydrochloride formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity, and photolytic degradation. Cinacalcet hydrochloride was found to degrade significantly under the peroxide stress conditions. The degradation products were well-resolved from cinacalcet hydrochloride and its impurities. The peak purity test results confirmed that the cinacalcet hydrochloride peak was homogenous in all stress samples and the mass balance was found to be more than 96%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines.

  9. Preparation and Identification of Major Impurity A in Pyridoxine Hydrochloride%维生素B6中关键杂质A的制备与分析

    Institute of Scientific and Technical Information of China (English)

    徐勇智; 范卫东; 章根宝; 党登峰

    2011-01-01

    Impurity A in European pharmacopoeia for pyridoxine hydrochloride was synthesized from pyridoxine hydrochloride with the presence of sulfuric acid, and its structure was characterized by lH NMR, MS, FT-IR, HPLC. This study provides a convenient method to prepare impurity A reference substance, which can be used for quality control of pyridoxine hydrochloride.%以维生素B6为起始原料,在硫酸存在下合成了欧洲药典中的维生素B6杂质A,并通过1H NMR、MS、FT-IR、HPLC方法对其结构进行鉴定,为生产维生素B6质量控制提供了一种简便的杂质标准物制备方法.

  10. A Post Hoc Analysis of D-Threo-Methylphenidate Hydrochloride (Focalin) Versus D,l-Threo-Methylphenidate Hydrochloride (Ritalin)

    Science.gov (United States)

    Weiss, Margaret; Wasdell, Michael; Patin, John

    2004-01-01

    Objective: To evaluate clinical measures of the benefit/risk ratio in a post hoc analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and d,l-threo-methylphenidate hydrochloride (d,l-MPH). Method: Data from a phase III clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment for…

  11. Simultaneous determination of nortriptyline hydrochloride and fluphenazine hydrochloride in microgram quantifies from low dosage forms by liquid chromatography-UV detection

    Institute of Scientific and Technical Information of China (English)

    Safwan Ashour; Nuha Kattan

    2012-01-01

    A novel method for the simultaneous high-performance liquid chromatographic determi- nation of nortriptyline hydrochloride and fluphenazine hydrochloride was developed and validated. Fhivastatin sodium was used as internal standard. The determination was performed on a Hypersil Gold Cs column (250 mm × 4.6 mm i.d., 5 μm particle size) at 25 ℃; the mobile phase, consisting of a mixture of formic acid (0.1 M, pH 2.16)-methanol (33:67, v/v), was delivered at a fow rate of 1.1 mL/min and detector wavelength at 251 rim. The retention time of nortriptyline, fluphenazine and fluvastatin was found to be 5.11, 8.05 and 11.38 min, respectively. Linearity ranges were 5.0-1350.0 and 10.0-1350.0 μg/ mL with limit of detection values of 0.72 and 0.31μg/mL, for nortriptyline and fluphenazine, respectively. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. Correlation coefficients (r2) of the regression equations were greater than 0.999 in all cases. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of nortriptyline and fluphenazine.

  12. A SIMPLE AND-SENSITIVE STABILITY-INDICATING UHPLC-DAD METHOD FOR THE DETERMINATION OF CEFETAMET PIVOXIL HYDROCHLORIDE.

    Science.gov (United States)

    Garbacki, Piotr; Cielecka-Piontek, Judyta; Zalewski, Przemysław; Oszczapowicz, Irena; Jelińska, Anna

    2016-01-01

    A fast and sensitive UHPLC-DAD method was developed and subsequently validated for determination of cefetamet pivoxil hydrochloride in the presence of its degradation products. The chromatographic separation was carried out on a Waters Acquity BEH C18, (2.1 x 100 mm, 1.7 µm) column. The mobile phase was composed of 0.1% formic acid and acetonitrile (40 : 60, v/v) at the flow rate 0.7 mL/min. The detection wavelength was 265 nm and the temperature was 30 °C. Cefetamet pivoxil hydrochloride was susceptible to degradation under the influence of sodium hydroxide, hydrochloric acid and in the conditions of increased temperature and relative humidity. However, it was stable after irradiation, in increased temperature in dry air and in the presence of oxidizing agent. The developed UHPLC-DAD method was linear over the concentration range of 10-240 µg/mL (r2 = 0.9999; n = 12). The obtained RSD values were less than 2%, demonstrating that the described procedure is precise. The accuracy was also confirmed (mean recoveries were 97.79-102.08%). Under applied chromatographic conditions LOD and LOQ values were 2.08 mg/mL and 6.29 mg/mL, respectively. The proposed method was successfully applied in determination of cefetamet pivoxil hydrochloride in aqueous solutions as well as in the solid state.

  13. Development of duloxetine hydrochloride loaded mesoporous silica nanoparticles: characterizations and in vitro evaluation.

    Science.gov (United States)

    Ganesh, Mani; Ubaidulla, Udhumansha; Hemalatha, Pushparaj; Peng, Mei Mei; Jang, Hyun Tae

    2015-08-01

    This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol-gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The "n" value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r (2)) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.

  14. Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.

    Science.gov (United States)

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Ionescu, Claudio; Dartizio, Carmela; Troplini, Sonila; Kunnathully, Vidya; Adami, Silvano; Rossini, Maurizio

    2014-10-01

    The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (posteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a late increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens.

  15. Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity

    Science.gov (United States)

    Gong, Xue; Yu, Wanlu; Zhao, Hang; Su, Jiansheng; Sheng, Qing

    2017-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research. PMID:28139685

  16. In vitro evaluation of the stability of ranitidine hydrochloride in total parenteral nutrient mixtures.

    Science.gov (United States)

    Williams, M F; Hak, L J; Dukes, G

    1990-07-01

    The stability of ranitidine hydrochloride in various total parenteral nutrient (TPN) solutions was studied, as well as the effect of ranitidine on the stability of lipid emulsion and amino acids in these solutions. Ranitidine hydrochloride 25 mg/mL was added to each of the following mixtures to make final concentrations of approximately 50 and 100 mg/L: (1) TPN solution containing 4.5% amino acids, 22.7% dextrose, and electrolytes; (2) 10% lipid emulsion; (3) TPN solution containing 3.7% amino acids, 18.5% dextrose, 3.7% lipid emulsion, and electrolytes (all-in-one mixture); and (4) 0.9% sodium chloride injection. Mixtures were tested at room temperature and at 4 degrees C and were either protected from or exposed to fluorescent light. Sampling was done at 0, 12, 24, 36, and 48 hours, and the ranitidine concentration was determined by high-performance liquid chromatography. Samples were also analyzed for lipid particle size distribution and for amino acid content. At 48 hours, the all-in-one mixtures retained 86.0% to 91.4% of the initial ranitidine concentration. With one exception (ranitidine 50 mg/L in 0.9% sodium chloride injection, stored at room temperature and not protected from light), all other solutions retained at least 90% of the initial concentration at 48 hours. No visible changes in color and minimal changes in pH values were noted. There were no important changes in lipid particle-size distribution; 96% of all particles counted from any mixture were smaller than 1.44 microns in diameter at 48 hours. Ranitidine did not have an effect on amino acid concentrations in these mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin.

    Science.gov (United States)

    Al-Khalili, Mohammad; Meidan, Victor M; Michniak, Bozena B

    2003-01-01

    The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm2 resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel resulted in a synergistic effect when combined with iontophoresis. Menthol was the most active enhancer, and when combined with iontophoresis it was possible to deliver 10 mg/cm2/day of buspirone hydrochloride.

  18. Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial

    DEFF Research Database (Denmark)

    Adachi, J D; Lyles, K W; Colón-Emeric, C S

    2011-01-01

    This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. INTRODUCTION: To e...

  19. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H;

    2013-01-01

    -specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six...

  20. Systemic effects of zoledronic acid in children with traumatic femoral head avascular necrosis and Legg-Calve-Perthes disease

    DEFF Research Database (Denmark)

    Johannesen, Jesper; Briody, Julie; McQuade, Mary;

    2009-01-01

    SD at 12 months follow-up. Biochemical markers of bone turnover were decreased and PTH increased during the first 12 months of treatment and bone modeling was reduced. All markers stabilised over the next 6 months. There were no incidences of fracture, spondylolisthesis or osteonecrosis of the jaw...

  1. HPLC法测定馥感啉口服液中盐酸麻黄碱和盐酸伪麻黄碱的含量%Determination of Ephedrine Hydrochloride and Pseudoephedrine Hydrochloride in Fuganlin Oral Liquid by HPLC

    Institute of Scientific and Technical Information of China (English)

    曾永长; 张莉; 曾晓燕; 陈艺文

    2015-01-01

    目的:采用高效液相色谱法建立同时测定馥感啉口服液中盐酸麻黄碱和盐酸伪麻黄碱含量的检测方法。方法使用Phenomenex Synergi Polar-RP柱(250 mm×4.6 mm,4μm),以甲醇-0.092%磷酸溶液(含0.04%三乙胺和0.02%二正丁胺)(1.5∶98.5)为流动相,流速:1.0 mL·min-1,检测波长为210 nm。结果盐酸麻黄碱和盐酸伪麻黄碱在进样1~100μg·mL-1范围内线性关系良好,平均回收率(n=6)分别为97.43%(RSD=0.80%)、98.59%(RSD=1.77%)。结论该方法操作简便、分离度好、稳定可靠,可同时快速测定盐酸麻黄碱和盐酸伪麻黄碱,为馥感啉口服液的质量评价提供科学依据。%Objective To establish a HPLC method to determine the content of ephedrine hydrochloride and pseudoephedrine hydrochloride in Fuganlin oral liquid. Methods The chromatographic conditions was as follows:Phenomenex Synergi Polar-RP column(250 mm ×4.6 mm, 4 μm), methanol-0.092 % phosphoric acid solution (containing 0.04 % triethylamine and 0.02 % di-n-butylamine)(1.5∶98.5)as the mobile phase, flow rate being 1.0 mL ·min-1, detection wavelength set as 210 nm. Results The linear range of ephedrine hydrochloride and pseudoephedrine hydrochloride was 1~100 μg·mL-1,and the average recovery(n=6)was 97.43 % (RSD=0.80 %) and 98.59 %(RSD=1.77 %)respectively. Conclusion The method is simple,accurate and reliable,and can be used for the simultaneous determination of ephedrine hydrochloride and pseudoephedrine hydrochloride,which will provide a scientific basis for quality evaluation of Fuganlin oral liquid.

  2. Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

    Science.gov (United States)

    Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

    2016-04-01

    A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

  3. 78 FR 2416 - Notice of Issuance of Final Determination Concerning Rybix® (Tramadol Hydrochloride) Tablets

    Science.gov (United States)

    2013-01-11

    ... (Tramadol Hydrochloride) Tablets AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... (tramadol hydrochloride) tablets. Based upon the facts presented, CBP has concluded in the final determination that India is the country of origin of the Rybix (tramadol hydrochloride) tablets for purposes of...

  4. Spectrophotometric determination of meclizine hydrochloride and pyridoxine hydrochloride in laboratory prepared mixtures and in their pharmaceutical preparation

    Science.gov (United States)

    Ibrahim, Maha M.; Elzanfaly, Eman S.; El-Zeiny, Mohamed B.; Ramadan, Nesreen K.; Kelani, Khadiga M.

    2017-05-01

    In this paper, three rapid, simple, accurate and precise spectrophotometric methods were developed for the determination of meclizine hydrochloride in the presence of pyridoxine hydrochloride without previous separation. The methods under study are dual wavelength (DWL), ratio difference (RD) and continuous wavelet transform (CWT). On the other hand, pyridoxine hydrochloride (PYH) was determined directly at 291 nm. The methods obey Beer's law in the range of (5-50 μg/mL) for both compounds. All the methods were validated according to the ICH guidelines where the accuracy was found to be 98.29, 99.59, 100.42 and 100.62% for DWL, RD, CWT and PYH; respectively. Moreover the precision of the methods were calculated in terms of %RSD and it was found to be 0.545, 0.372, 1.287 and 0.759 for DWL, RD,CWT and PYH; respectively. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of pyridoxine hydrochloride and meclizine hydrochloride in quality-control laboratories.

  5. Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

    Directory of Open Access Journals (Sweden)

    Saburo Minami

    2012-08-01

    Full Text Available D-Glucosamine hydrochloride (GlcN∙HCl is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β.

  6. Stability of ranitidine hydrochloride in total parenteral nutrient solution.

    Science.gov (United States)

    Walker, S E; Bayliff, C D

    1985-03-01

    The stability of ranitidine hydrochloride was studied in a standard total parenteral nutrition (TPN) solution. The Canadian formulation of ranitidine hydrochloride (25 mg/mL) was added in 100-, 200-, and 300-mg doses to approximately 1200 mL of a TPN solution and allowed to stand at room temperature (23 degrees C) for seven days. During this time, samples were drawn at least once a day, and the ranitidine concentration was determined by high-performance liquid chromatography. The ranitidine concentration declined at roughly the same rate regardless of the initial concentration. During the study period, each of the three different concentrations declined to less than 70% of the initial concentration. Approximately 10% of the initial concentration was lost in 48 hours. Ranitidine hydrochloride admixtures were stable for up to 48 hours at room temperature in this standard TPN solution.

  7. Temperature-dependent THz vibrational spectra of clenbuterol hydrochloride

    Science.gov (United States)

    Yang, YuPing; Lei, XiangYun; Yue, Ai; Zhang, Zhenwei

    2013-04-01

    Using the high-resolution Terahertz Time-domain spectroscopy (THz-TDS) and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride (CH), a β 2-adrenergic agonist for decreasing fat deposition and enhancing protein accretion, were measured in temperature range of 77-295 K. Between 0.2 and 3.6 THz (6.6-120.0 cm-1), seven highly resolved spectral features, strong line-narrowing and a frequency blue-shift were observed with cooling. However, ractopamine hydrochloride, with some structural and pharmacological similarities to clenbuterol hydrochloride, showed no spectral features, indicating high sensitivity and strong specificity of THz-TDS. These results could be used for the rapid and nondestructive CH residual detection in food safety control.

  8. Simultaneous spectrophotometric determination of drotaverine hydrochloride and paracetamol in tablet.

    Science.gov (United States)

    Mahaparale, Sonali; Telekone, R S; Raut, R P; Damle, S S; Kasture, P V

    2010-01-01

    Two simple, accurate and reproducible spectrophotometric methods; Q analysis and first order derivative method have been described for the simultaneous estimation of drotaverine hydrochloride and paracetamol in combined tablet dosage form. Absorption maxima of drotaverine hydrochloride and paracetamol in distilled water were found to be 303.5 nm and 243.5 nm respectively. Beer's law was obeyed in the concentration range 5-50 mug/ml for drotaverine and 5-60 mug/ml for paracetamol. In Q analysis method, two wavelengths were selected at isobestic point (277 nm) and lambda(max) of paracetamol (243.5 nm). In first order derivative method, zero crossing point for drotaverine hydrochloride and paracetamol were selected at 303.5 nm and 243.5 nm, respectively. The results of two methods were validated statistically and recovery studies were found to be satisfactory.

  9. Simultaneous spectrophotometric determination of drotaverine hydrochloride and paracetamol in tablet

    Directory of Open Access Journals (Sweden)

    Mahaparale Sonali

    2010-01-01

    Full Text Available Two simple, accurate and reproducible spectrophotometric methods; Q analysis and first order derivative method have been described for the simultaneous estimation of drotaverine hydrochloride and paracetamol in combined tablet dosage form. Absorption maxima of drotaverine hydrochloride and paracetamol in distilled water were found to be 303.5 nm and 243.5 nm respectively. Beer′s law was obeyed in the concentration range 5-50 µg/ml for drotaverine and 5-60 µg/ml for paracetamol. In Q analysis method, two wavelengths were selected at isobestic point (277 nm and λmax of paracetamol (243.5 nm. In first order derivative method, zero crossing point for drotaverine hydrochloride and paracetamol were selected at 303.5 nm and 243.5 nm, respectively. The results of two methods were validated statistically and recovery studies were found to be satisfactory.

  10. Manipulating the anabolic and catabolic response in bone graft remodeling: synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate.

    Science.gov (United States)

    Harding, Anna Kajsa; Aspenberg, Per; Kataoka, Masashi; Bylski, David; Tägil, Magnus

    2008-09-01

    Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p < 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. (c) 2008 Orthopaedic Research Society

  11. Splenic fibrosis and sarcomas in F344 rats fed diets containing aniline hydrochloride, p-chloroaniline, azobenzene, o-toluidine hydrochloride, 4,4'-sulfonyldianiline, or D & C red No. 9.

    Science.gov (United States)

    Goodman, D G; Ward, J M; Reichardt, W D

    1984-07-01

    In six carcinogenicity bioassays, male and female F344 rats were fed diets containing aniline hydrochloride (CAS: 142-04-1; hydrochloride benzenamide), p-chloroaniline (CAS: 106-47-8), azobenzene (CAS: 103-33-3), o-toluidine hydrochloride (CAS: 636-21-5), dapsone (CAS: 80-08-0; 4,4'-sulfonyldianiline), or D & C red No. 9 [CAS: D85500000; 5-chloro-2-[2-hydroxy-1-naphthalenyl)azo)-4-methylbenzenesulfon ic acid, barium salt]. The rats, from 6 weeks to 2 years old, were given the compounds at two dose levels, the estimated maximum tolerated dose and one-half that dose. In all six bioassays, dose-dependent incidences of splenic sarcomas and fibrosis were seen, with the highest incidences in male rats. Fibrosis occurred in the splenic parenchyma and/or the capsule. Fatty infiltration also was seen in the spleen. Sarcomas appeared to arise in the splenic red pulp or splenic capsule, usually in association with areas of parenchymal and capsular fibrosis and pigmentation. Larger tumors metastasized to the peritoneal cavity and abdominal organs. In some rats there was marked osseous metaplasia when the primary tumor metastasized to peritoneal surfaces. Other, less common, splenic neoplasms included hemangiosarcoma and hemangiopericytoma. Some rats had such extensive peritoneal involvement that the site of origin of their sarcoma was difficult to determine.

  12. Spectrophotometric determination of ritodrine and isoxsuprine hydrochlorides using 4-aminoantipyrine.

    Science.gov (United States)

    Revanasiddappa, H D; Manju, B G

    2000-01-01

    A simple, accurate, and rapid method for the quantitative determination of ritodrine hydrochloride (RTH) and isoxsuprine hydrochloride (ISH) in both pure and dosage forms, is described. The method is based on the development of pink colored product as a result of the condensation of 4-aminoantipyrine with phenols in the presence of an alkaline oxidizing agent. The resulting products are measured at 510 nm for both drugs, with molar absorptivities of 0.98 x 10(4) and 1.20 x 10(4) L/mol x cm for RTH and ISH, respectively. A study of the effect of commonly associated excipients revealed that they did not cause interference.

  13. Enantiomeric Separation of Meptazinol Hydrochloride by Capillary Electrophoresis

    Institute of Scientific and Technical Information of China (English)

    YUYun-qiu; CHENYan; LINi; QIUZhui-bai

    2004-01-01

    Aim To establish a capillary electrophoresis method for enantiomerie separation of meptazinol hydrochloride. Methods The separation conditions such as cyclodextrin(CD)type, buffer pH, concentration of 2,3,6-O-triInethyl-β-cyclodextrin and organic additives were optimized. An optimum concentration was 30 mmol·L-1 phosphate (pH 7.02)with 10% (W/V) TM-β-CD and 2% acetonitrile. Results Basehne resolution of the enantiomer was readily achieved using 2,3,6-O-trimethyl-β-cyclodextrin. Conclusion This is a convenient method for fast enantiomeric resolution of meptazinol hydrochloride.

  14. [Effect of topical exhedrine hydrochloride on muco-ciliary transport].

    Science.gov (United States)

    Grammatica, L; Fiorella, R

    1983-07-30

    The time of nasal M.C.T. (Mucus Ciliar Transport) was studied by the indirect objective method of bleu-sky in 30 healthy subjects before and after the application of efedrina hydrochloride in water solution associated with timolo, eucaliptolo, mentolo essence of canfora monobramata and clorbutamolo. The time of nasal M.C.T., regular in the 87% of the subjects during the first determination was found extended in almost all of the cases after the application of vasoconstrictor (85%). This experimental data may be caused both by a direct effect of efedrina hydrochloride and by the substances associated in the solution and their physical characteristics.

  15. Preparation and adsorption behavior of berberine hydrochloride imprinted polymers by using silica gel as sacrificed support material

    Science.gov (United States)

    Li, Hui; Li, Yuzhuo; Li, Zhiping; Peng, Xiyang; Li, Yanan; Li, Gui; Tan, Xianzhou; Chen, Gongxi

    2012-03-01

    Preparation of berberine hydrochloride (B-Cl) imprinted polymers (MIPs) based on surface imprinting technique with silica gel as sacrificial support material was performed successfully by using B-Cl as template, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The prepared polymers were characterized by Fourier transmission infrared spectrometry (FTIR) and scanning electron microscopy (SEM). Adsorption behavior of the MIPs for the template and its structural analogues was investigated. Sites distribution on the surface of MIPs was explored by using different isotherm adsorption models and thermodynamic parameters for the adsorption of B-Cl on the MIPs determined. Sample application and reusability for the MIPs was also evaluated. Results indicated the strong adsorption and high selectivity of the MIPs for B-Cl. Saturated adsorption capacity reached 27.2 μmol g-1 and the selectivity coefficient of the MIPs for B-Cl relative to jatrorrhizine hydrochloride (J-Cl) and palmatine palmatus hydrochloride (P-Cl) are 3.70 and 6.03, respectively. In addition, the MIPs were shown with good reusability and selectively retention ability in sample application.

  16. Preparation and adsorption behavior of berberine hydrochloride imprinted polymers by using silica gel as sacrificed support material

    Energy Technology Data Exchange (ETDEWEB)

    Li Hui, E-mail: lihuijsdx@163.com [Key Laboratory of Plant Resource Conservation and Utilization, Jishou University, Hunan Jishou, 416000 (China); Li Yuzhuo [Key Laboratory of Plant Resource Conservation and Utilization, Jishou University, Hunan Jishou, 416000 (China); Li Zhiping [College of Chemistry and Chemical Engineering, Jishou University, Hunan Jishou, 416000 (China); Peng Xiyang; Li Yanan; Li Gui; Tan Xianzhou; Chen Gongxi [Key Laboratory of Plant Resource Conservation and Utilization, Jishou University, Hunan Jishou, 416000 (China)

    2012-03-01

    Preparation of berberine hydrochloride (B-Cl) imprinted polymers (MIPs) based on surface imprinting technique with silica gel as sacrificial support material was performed successfully by using B-Cl as template, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The prepared polymers were characterized by Fourier transmission infrared spectrometry (FTIR) and scanning electron microscopy (SEM). Adsorption behavior of the MIPs for the template and its structural analogues was investigated. Sites distribution on the surface of MIPs was explored by using different isotherm adsorption models and thermodynamic parameters for the adsorption of B-Cl on the MIPs determined. Sample application and reusability for the MIPs was also evaluated. Results indicated the strong adsorption and high selectivity of the MIPs for B-Cl. Saturated adsorption capacity reached 27.2 {mu}mol g{sup -1} and the selectivity coefficient of the MIPs for B-Cl relative to jatrorrhizine hydrochloride (J-Cl) and palmatine palmatus hydrochloride (P-Cl) are 3.70 and 6.03, respectively. In addition, the MIPs were shown with good reusability and selectively retention ability in sample application.

  17. A comparative study on the aggregating effects of guanidine thiocyanate, guanidine hydrochloride and urea on lysozyme aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Emadi, Saeed, E-mail: emadi@iasbs.ac.ir; Behzadi, Maliheh

    2014-08-08

    Highlights: • Lysozyme aggregated in guanidine thiocyanate (1.0 and 2.0 M). • Lysozyme aggregated in guanidine hydrochloride (4 and 5 M). • Lysozyme did not aggregated at any concentration (0.5–5 M) of urea. • Unfolding pathway is more important than unfolding per se in aggregation. - Abstract: Protein aggregation and its subsequent deposition in different tissues culminate in a diverse range of diseases collectively known as amyloidoses. Aggregation of hen or human lysozyme depends on certain conditions, namely acidic pH or the presence of additives. In the present study, the effects on the aggregation of hen egg-white lysozyme via incubation in concentrated solutions of three different chaotropic agents namely guanidine thiocyanate, guanidine hydrochloride and urea were investigated. Here we used three different methods for the detection of the aggregates, thioflavin T fluorescence, circular dichroism spectroscopy and atomic force microscopy. Our results showed that upon incubation with different concentrations (0.5, 1.0, 2.0, 3.0, 4.0, 5.0 M) of the chemical denaturants, lysozyme was aggregated at low concentrations of guanidine thiocyanate (1.0 and 2.0 M) and at high concentrations of guanidine hydrochloride (4 and 5 M), although no fibril formation was detected. In the case of urea, no aggregation was observed at any concentration.

  18. [Simultaneous determination of ephedrine hydrochloride, D-pseudoephedrine and amygdalin in xiao'er pingchuan qutan granule by HPLC].

    Science.gov (United States)

    Yang, De-Bin; Tong, Yan; Ma, Zhen-Shan; Wang, Lin; Dong, Mei-Hong; Li, Yan-Ling; Wang, Jin-Yu

    2013-03-01

    To establish an HPLC method for the determination of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule. Pheny ether chromatographic column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.1% phosphoric acid (containing 0.1% three ethylamine) (3:97) as the mobile phase. The UV detection wavelength was at 210 nm, with the flow rate of 1 mL x min(-1), and column temperature was at 35 degrees C. The linearity of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin ranged between 0.078 60-3.144 microg (r = 1.000 0), 0.103 4-2.068 microg (r = 0.999 7) and 0.430 5-3.157 microg (r = 0.999 8), respectively. Their average recoveries were 98.46% (RSD 1.1%), 103.0% (RSD 1.5%) and 97.15% (RSD 2.1%), respectively. The method is simple, stable and reliable that it can be used to determine the content of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule.

  19. Stability-indicating LC method for the estimation of bendamustine hydrochloride and its related impurities.

    Science.gov (United States)

    Kasa, Srinivasulu; Raja Sekhar Reddy, M; Kadaboina, Raja Sekhar; Murki, Veerender; Mulukutla, Venkata Suryanarayana

    2014-08-01

    A novel, simple, sensitive and stability-indicating high-performance liquid chromatography method was developed and validated for the quantification of impurities (process related and degradants) and the assay determination of Bendamustine hydrochloride. A chromatographic separation of Bendamustine and its impurities was achieved with an Inertsil ODS-2 analytical column, 250 × 4.6 mm, 5 µm, using gradient elution with mobile phase A consisting of a mixture of water and trifluoroacetic acid (1000:1, v/v) and mobile phase B consisting of acetonitrile. The instrumental settings included a flow rate of 1.0 mL/min, column temperature of 27°C and a detector wavelength of 233 nm, using a photodiode array detector. The tailing factor for Bendamustine was 1.10. Bendamustine hydrochloride was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions and the stressed samples were analyzed by the proposed method. Peak homogeneity data of Bendamustine were obtained by using a photodiode array detector in the stressed sample chromatograms, which demonstrated the specificity of the method for estimation in the presence of degradants. The developed method was validated for parameters such as precision, accuracy, linearity, limit of detection, limit of quantification, ruggedness and robustness. The stability tests were also performed on drug substances as per International Conference on Harmonization guidelines.

  20. Development and validation of RP-HPLC method for the estimation of ivabradine hydrochloride in tablets

    Directory of Open Access Journals (Sweden)

    Seerapu Sunitha

    2010-01-01

    Full Text Available A simple, sensitive, precise and robust reverse-phase high-performance liquid chromatographic method for analysis of ivabradine hydrochloride in pharmaceutical formulations was developed and validated as per ICH guidelines. The separation was performed on SS Wakosil C18AR, 250Χ4.6 mm, 5 μm column with methanol:25 mM phosphate buffer (60:40 v/v, adjusted to pH 6.5 with orthophosphoric acid, added drop wise, as mobile phase. A well defined chromatographic peak of Ivabradine hydrochloride was exhibited with a retention time of 6.55±0.05 min and tailing factor of 1.14 at the flow rate of 0.8 ml/min and at ambient temperature, when monitored at 285 nm. The linear regression analysis data for calibration plots showed good linear relationship with R=0.9998 in the concentration range of 30-210 μg/ml. The method was validated for precision, recovery and robustness. Intra and Inter-day precision (% relative standard deviation were always less than 2%. The method showed the mean % recovery of 99.00 and 98.55 % for Ivabrad and Inapure tablets, respectively. The proposed method has been successfully applied to the commercial tablets without any interference of excipients.

  1. Charge-assisted bond N(+)H mediates the gelation of amorphous lurasidone hydrochloride during dissolution.

    Science.gov (United States)

    Qian, Shuai; Wang, Shanshan; Li, Zhen; Wang, Xiaojie; Ma, Di; Liang, Shujun; Gao, Yuan; Zhang, Jianjun; Wei, Yuanfeng

    2017-02-25

    Lurasidone hydrochloride (LH), the hydrochloride form of lurasidone with a charge-assisted bond N(+)H, is an atypical antipsychotropic agent for the treatment of schizophrenia. As a BCS class II drug, LH has a low oral bioavailability mainly due to its poor water solubility and low dissolution. In order to improve its solubility, amorphization of LH was performed and characterized. Unexpectedly, the dissolution rate of amorphous LH was much lower than that of crystalline LH. In addition, the amorphous LH powders quickly aggregated when contacting the dissolution media (water, 37°C), and formed a sticky gel adhering on the paddle. The follow-up polarized light microscope, XRPD, DSC, and FTIR analysis found that amorphous LH transformed to crystalline LH during dissolution. On the other hand, no such gelation phenomenon of amorphous lurasidone was observed under the same dissolution condition. However, the gel would reform when dropping concentrated hydrochloric acid slowly into the bottom of the medium during the dissolution of amorphous lurasidone, and XRPD/DSC/FTIR results indicated that the regenerated gel was consisted of crystalline LH, suggesting that the charge-assisted bond N(+)H in the structure of LH mediated the gel formation of amorphous LH during its dissolution process.

  2. [Radiolytic Decomposition of Ciprofloxacin Hydrochloride in Aqueous Solution Using γ Irradiation].

    Science.gov (United States)

    Zhu, Sheng-nan; Guo, Zhao-bing; Zhao, Yong-fu; Ge, Xin; Wei, Ying; Chen, Shu; Wang, Jing

    2015-04-01

    Effects of initial concentrations, pH values, different additives and composite pollutants on ciprofloxacin hydrochloride removal using γ irradiation were investigated. The experiments results showed γ irradiation could effectively remove ciprofloxacin hydrochloride; low initial concentration and strongly acidic condition were favorable for CIP removal using γ irradiation; the degradation of CIP was inhibited upon the addition of CO3(2-) and methanol, which indicated that the degradation of CIP might be mainly ascribed to *OH oxidation and the direct decomposition of CIP molecules induced by irradiation. BrO3- showed a synergistic effect with CIP in degradation of the composite pollutants when mixed together with CIP for γ irradiation, and the removal rates of both pollutants were improved. At an absorbed dose of 400 Gy, the removal rates of CIP and BrO3- were increased by 18.74% and 1.81%, respectively. The removal rates of TOC and COD were 15.22% and 61.44%, respectively, when the 100 mg x L(-1) CIP was degraded by γ irradiation at the absorbed dose of 6 000 Gy.

  3. Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

    Directory of Open Access Journals (Sweden)

    Y. Ankamma Chowdary

    2014-01-01

    Full Text Available In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms.

  4. Determination of Dyclonine Hydrochloride by a HPLC Method and Camphor and Menthol by a GC Method in Compound Lotion

    Directory of Open Access Journals (Sweden)

    Suying Ma

    2013-01-01

    Full Text Available A high performance liquid chromatographic (HPLC method with UV detector for the determination of dyclonine hydrochloride and a gas chromatography (GC method with flame ionization detector (FID for the determination of camphor and menthol in lotion were developed. The developed HPLC method involved using a SinoChoom ODS-BP C18 reversed-phase column (5 μm, 4.6 mm × 200 mm and mobile phase consisting of acetonitrile : water : triethylamine in a ratio of 45 : 55 : 1.0; pH was adjusted to 3.5 with glacial acetic acid. The developed GC method for determination of camphor and menthol involved using an Agilent 19091J-413 capillary chromatographic column (30 m × 320 μm × 0.25 μm. The two methods were validated according to official compendia guidelines. The calibration of dyclonine hydrochloride for HPLC method was linear over the range of 20–200 μg/mL. The retention time was found at 6.0 min for dyclonine hydrochloride. The calibration of camphor and menthol of GC method was linear over the range of 10–2000 μg/mL. The retention time was found at 2.9 min for camphor and 3.05 min for menthol. The proposed HPLC and GC methods were proved to be suitable for the determination of dyclonine hydrochloride, camphor, and menthol in lotion.

  5. Diffusion Coefficients ofl-Lysine Hydrochloride and l-Arginine Hydrochloride in Their Aqueous Solutions at 25℃

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The diffusion coefficients** ofl-lysine hydrochloride andl-arginine hydrochloride in their aqueous solu- tions at 25℃ were determined by the metallic diaphragm cell method which is characterized by accuracy, promptness and convenience. Meanwhile, the densities and viscosities of the solutions were also determined. Based on all these data a semi-empirical model for correlating the diffusion coefficients of solid organic salts in their aqueous solutions at 25℃ was proposed. The fitting result of this model is comparatively satisfactory. Compared to a former model, Gordon Model, this model can avoid a number of difficulties and arduous work.

  6. Release Characteristics of Diltiazem Hydrochloride Wax-Matrix ...

    African Journals Online (AJOL)

    Michael Horsfall

    diltiazem hydrochloride-wax matrix granules with sintering. ... The drug release was by Higuchi controlled diffusion mechanism and it followed ... of plastic matrix tablets. Polymer films with different permeability have been .... More so, with increase in temperature and ..... characterization of ibuprofen-cetyl alcohol beads by.

  7. Surface tension of compositions of polyhexametyleneguanidine hydrochloride - surfactants

    Directory of Open Access Journals (Sweden)

    S. Kumargaliyeva

    2012-12-01

    Full Text Available We made up songs bactericidal polyhexamethyleneguanidine hydrochloride (metacyde with the surface-active substances - anionic sodium dodecylsulfate, cationic cetylpyridinium bromide, and nonionic Tween-80 and measured the surface tension of water solutions. The study showed that the composition metacyde with surface-active agents have a greater surface activity than the individual components.

  8. 21 CFR 524.1982 - Proparacaine hydrochloride ophthalmic solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Proparacaine hydrochloride ophthalmic solution. 524.1982 Section 524.1982 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... longterm toxicity of proparacaine is unknown. Prolonged use may possibly delay wound healing. (d...

  9. Acute generalized exanthematous pustulosis caused by terazosin hydrochloride.

    Science.gov (United States)

    Speck, Laura M; Wilkerson, Michael G; Perri, Anthony J; Kelly, Brent C

    2008-04-01

    Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption mainly provoked by drugs. A case of AGEP in a 74-year-old male that was attributed to the ingestion of terazosin hydrochloride is presented. This is the first reported case of this association in medical literature. The history, clinical presentation, and pathogenesis of AGEP are discussed.

  10. Cradle-to-gate life cycle inventory of vancomycin hydrochloride.

    Science.gov (United States)

    Ponder, Celia; Overcash, Michael

    2010-02-15

    A life cycle analysis on the cradle-to-gate production of vancomycin hydrochloride, which begins at natural resource extraction and spans through factory (gate) production, not only shows all inputs, outputs, and energy usage to manufacture the product and all related supply chain chemicals, but can highlight where process changes would have the greatest impact on raw material and energy consumption and emissions. Vancomycin hydrochloride is produced by a low-yield fermentation process that accounts for 47% of the total cradle-to-gate energy. The fermentation step consumes the most raw materials and energy cradle-to-gate. Over 75% of the total cradle-to-gate energy consumption is due to steam use; sterilization within fermentation is the largest user of steam. Aeration and agitation in the fermentation vessels use 65% of the cradle-to-gate electrical energy. To reduce raw materials, energy consumption, and the associated environmental footprint of producing vancomycin hydrochloride, other sterilization methods, fermentation media, nutrient sources, or synthetic manufacture should be investigated. The reported vancomycin hydrochloride life cycle inventory is a part of a larger life cycle study of the environmental consequences of the introduction of biocide-coated medical textiles for the prevention of MRSA (methicillin-resistant Staphylococcus aureus) nosocomial infections.

  11. Asymmetric Synthesis of (+)-(11 R,12S)-Mefloquine Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The asymmetric synthesis of (+)-(11R,12S)-mefloquine hydrochloride, an antimalarial drug, was accomplished from commercially available 2-trifluoromethylaniline, ethyl 4,4,4-trifluoroacetoacetate and cyclopentanone in 7 steps with a 14% overall yield. The key steps were proline-catalyzed asymmetric direct aldol reaction and Beck-mann rearrangement. The absolute configuration was assigned by a Mosher's method.

  12. Amitriptyline-related peripheral neuropathy relieved during pyridoxine hydrochloride administration.

    Science.gov (United States)

    Meadows, G G; Huff, M R; Fredericks, S

    1982-11-01

    Tricyclic antidepressants rarely cause peripheral neuropathy. In fact, this class of drugs has been used to control the symptoms of pain and paresthesia that accompany peripheral neuropathy. We report peripheral paresthesias that occurred in a 39-year-old female during five years of amitriptyline administration. The patient's symptoms were relieved by oral pyridoxine hydrochloride, associated with elevated plasma pyridoxal phosphate.

  13. Simple spectrophotometric methods for determination of fluoxetine and clomipramine hydrochlorides in dosage forms and in some post-mortem biological fluids samples

    Directory of Open Access Journals (Sweden)

    Emam A. Ali

    2016-12-01

    Full Text Available Sensitive, simple and rapid spectrophotometric methods for micro determination of fluoxetine hydrochloride (FLU and clomipramine hydrochloride (CLO. The methods are based on the reaction between the examined drugs and acid dyes, namely; bromocresol green (BCG, phenol red (PhR and metanil yellow (MY producing yellow ion-pair complexes followed by their extraction with methylene chloride and measured at 412, 407 and 409 nm for FLU with BCG, PhR and MY, respectively; whereas for CLO at 409, 406 and 407 nm, respectively. All variables that affect the performance of the proposed methods were carefully studied and optimized. Beer’s law was obeyed in the concentration ranges 0.86–24.32 μg/mL, 8.64–41.30 μg/mL, 0.86–34.76 μg/mL for FLU and 1.75–24.55 μg/mL, 7.0–50 μg/mL, 1.65–34.78 μg/mL for CLO using BCG, PhR and MY respectively. The methods were validated in terms of accuracy and precision. The proposed methods were successfully applied to the determination of fluoxetine hydrochloride and clomipramine hydrochloride in pure samples, pharmaceutical formulations, spiked post-mortem urine and blood samples.

  14. Micellization behavior of mixtures of amphiphilic promazine hydrochloride and cationic aniline hydrochloride in aqueous and electrolyte solutions

    Energy Technology Data Exchange (ETDEWEB)

    Rub, Malik Abdul; Azum, Naved; Asiri, Abdullah M. [King Abdulaziz University, Jeddah (Saudi Arabia); Khan, Farah [Aligarh Muslim University, Aligarh (India); Al-Sehemi, Abdullah G. [Research Center for Advanced Materials Science, King Khalid University, Abha (Saudi Arabia)

    2015-10-15

    We studied the influence of cationic hydrotrope aniline hydrochloride on the micellization behavior of cationic amphiphilic phenothiazine drug promazine hydrochloride in the presence and absence of 50mmol kg{sup -1} NaCl. The experimental critical micelle concentration (CMC) values came out to be lower than ideal CMC (CMCid) values, signifying attractive interactions between the two components in mixed micelles. NaCl further decreases the CMC of pure PMZ and aniline hydrochloride as well as their mixture due to screening of the electrostatic repulsion among the polar head groups. The bulk properties of solution were examined by using different theoretical models for justification and comparison of results. The micellar mole fraction of aniline hydrochloride (X{sup Rub}{sub ,} X{sup M}{sub 1}, X{sup Rod}{sub 1} and X{sup id}{sub 1}) was evaluated by different proposed models, showing greater contribution of hydrotrope in mixed micelle. The negative values of interaction parameter (β) indicate synergistic interactions and negative values of β further decrease by the addition of salt in mixed systems. From the CMC values as a function of temperature, various thermodynamic properties have been evaluated and discussed in detail.

  15. Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values.

    Science.gov (United States)

    Veeraselvam, M; Sridhar, R; Perumal, P; Jayathangaraj, M G

    2014-01-01

    The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P sloth bears for appropriate line treatment.

  16. Chemical Immobilization of Sloth Bears (Melursus ursinus with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

    Directory of Open Access Journals (Sweden)

    M. Veeraselvam

    2014-01-01

    Full Text Available The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV, hemoglobin (Hb, red blood cell count (RBC, erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN, creatinine, alkaline amino-transferase (ALT, aspartate amino-transferase (AST, and so forth were estimated in 11 (5 males and 6 females apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P<0.05 and mean corpuscular hemoglobin concentration (MCHC (P<0.05. The study might help to evaluate health profiles of sloth bears for appropriate line treatment.

  17. 盐酸氨基葡萄糖片高效液相色谱测定方法的改进%Improvement on Determination of Glucosamine Hydrochloride in Glucosamine Hydrochloride Tablets by HPLC

    Institute of Scientific and Technical Information of China (English)

    吴学军; 金鹏飞; 邹定; 姜文清; 胡欣; 孙春华

    2012-01-01

    Objective To improve an HPLC method for the determination of glucosamine hydrochloride in Glucosamine Hydrochloride Tablets. Methods An Alltima C18 column (250 mm × 4. 6 mm, 5 μm) was used for the separation, with 10 mm ammonium dihydrogen phosphate - acetonitrile (95 : 5) as the mobile phase at the flow rate of 0.5 mL/min. The detection wavelength was 194 nm. Results This method showed good linearity with a correlation coefficient (r) of 0.999 5; the specificity study showed satisfactory resolutions between glucosamine hydrochloride, excipients, forced degradation products and common acid radical negative ions; the precisions and stability were satisfactory with all RSDs below 2% ; and the spiked recovery ranged from 99.52% to 101. 2%. Conclusion This method is superior to the standard method, and could be used for the determination of glucosamine hydrochloride in Glucosamine Hydrochloride Tablets.%目的 改进盐酸氨基葡萄糖片的高效液相色谱测定方法.方法 采用AlhimaC18色谱柱(250mm×4.6mm,5μm),以10mmol/L磷酸二氢铵溶液一乙腈(95:5,V/V)为流动相,流速为0.5 mL/min,检测渡长为194nm.结果 改进方法后,盐酸氨基葡萄糖的线性关系良好,r=0.999 5;方法专属性强,盐酸氨基葡萄糖和辅料、降解产物、常见酸根离子之间都有良好分离度;方法精密度和稳定性良好.RSD均小于2%;加样回收率良好,百分回收率在99.52%-101.2%之间.结论 改进后的方法优于国家食品药品监督管理局注册标准中的方法,可作为盐酸氨基葡萄糖片的含量测定方法.

  18. Bioadhesive ranitidine hydrochloride for gastroretention with controlled microenvironmental pH.

    Science.gov (United States)

    Adhikary, Anuradha; Vavia, Pradeep R

    2008-08-01

    Ranitidine hydrochloride is a H(2) receptor blocker used in the treatment of gastric ulcers. Pharmacological factors, in addition to the dosage regimen, favor development of a sustained-release system for ranitidine especially in the therapeutic condition of erosive esophagitis. This investigation delves into the development of bioadhesive type of gastroretentive formulation (tablets) of ranitidine. The effect of mucoadhesive polymers such as Carbopol, hydroxypropyl methyl cellulose, and dextrose were studied. Mucoadhesion, in vitro drug release profile, water uptake, and swelling of the tablet were evaluated. Alkalizing agents were incorporated in an attempt to maintain an alkaline microenvironment within the tablet and improve the stability of the drug in acidic medium. The stability was evaluated using dye test and degradation studies. The drug release profiles were fit into various kinetic models.

  19. [Qualitative and quantitative analysis of fluoxetine hydrochloride by 19F NMR].

    Science.gov (United States)

    Yang, Bai-Qin; Kong, Er-Li; Xue, Xiao-Di; Zhao, Shou-Qian; Lin, Shrong-Shi

    2012-05-01

    The chemical shift of fluoxetine hydrochloride appears at delta 14.15 in 19F NMR analysis. The delta moved upfield slightly from 14.158 to 14.145 when the concentration of solution became diluted from 2.00 to 0.05 mmol x L(-1). Spiking test was suggested to confirm the existence of the compound for qualitative analysis. 19F NMR detection sensitivity test illustrated that a concentration of 17 mg in 1 L water could be detected while the sample was scanned 500 times with optimum parameters. In quantitative analysis, standard curve of concentration versus fluorine signal intensity was proposed to determine the amount of fluoxetine. Long capillary tube containing trifluoroacetic acid was used as internal standard for the integration measurements and straight line was obtained with good fitting. Direct additions of trifluoroethanol to fluoxetine solutions gave a poorer standard curve.

  20. Rapid quantification of the metabolite of valacyclovir hydrochloride in human plasma by liquid chromatography-tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To establish a rapid,sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of acyclovir (the metabolite of valacyclovir hydrochloride) in human plasma. Methods After addition of ganciclovir as internal standard (IS),plasma samples were prepared by one-step protein precipitation using acetonitrile as precipitant,followed by an isocratic elution with 0.1% formic acid solution-methanol (95∶5,v/v) on an Agilent ZORBAX SB-C18 (150mm×2.1mm i.d.,3....

  1. Determination of Ephedrine Hydrochloride and Pseudoephedrine Hydrochloride in Heat Oral Solution for Children by HPLC%HPLC法测定小儿清热止咳口服液中盐酸麻黄碱和盐酸伪麻黄碱的含量

    Institute of Scientific and Technical Information of China (English)

    覃晓媚; 韦薇; 黄妹春; 周征福; 陆红萍; 陈晓军; 黄园

    2012-01-01

    The HPLC determination method was used to detect the ephedrine hydrochloride and pseudoephedrine hydrochloride in heat oral solution for children by C18 ( 4. 6 mmX 250mm, 5jum ) and methanol-0. 02mol/L sodium dihydrogen phosphate ( with 0. 2% triethylamine,adjusted with phosphoric acid pH = 2. 5,9 : 91 ) were used as the mobile phase. The flow was set at 1.0ml · min-1,and the detection wavelength was 210nm. The precision and stability were fine in those conditions. The calibration curve was linear over the range of 0. 102 ~1. 02jig for ephedrine hydrochloride ( r =0. 9999 ) and 0.1016~1. 6256jj.g for pseudoephedrine hydrochloride ( r =0. 9999 ). The average recovery rates ( n =6 ) was 97. 62% for ephedrine hydrochloride and 97. 55% for pseudoephedrine hydrochloride. The proposed method can be used in simultaneously quantitative analysis of ephedrine hydrochloride and pseudoephedrine hydrochloride in heat oral solution for children.%采用C18色谱柱(4.6 mmX250mm,5μm),以甲醇-0.02mol/L磷酸二氢钠溶液(含0.2%三乙胺,磷酸调pH值2.5,9:91)为流动相,流速1.0ml.rnin-1,检测波长210nm,建立反相高效液相色谱法测定小儿清热止咳口服液中盐酸麻黄碱和盐酸伪麻黄碱含量.结果表明,盐酸麻黄碱在0.102~1.02μg范围内与峰面积呈良好线性关系,r=0.9999,平均加样回收率为97.62%,RSD为1.56%(n=6);盐酸伪麻黄碱在0.1016~1.6256μg范围内与峰面积呈良好线性关系,r=0.9999,平均加样回收率为97.55%,RSD为1.84%(n=6).本方法分离度好,具有良好的重复性,可以同时测定小儿清热止咳口服液中盐酸麻黄碱和盐酸伪麻黄碱的含量.

  2. A Convenient Synthesis of Amino Acid Methyl Esters

    Directory of Open Access Journals (Sweden)

    Yaowu Sha

    2008-05-01

    Full Text Available A series of amino acid methyl ester hydrochlorides were prepared in good toexcellent yields by the room temperature reaction of amino acids with methanol in thepresence of trimethylchlorosilane. This method is not only compatible with natural aminoacids, but also with other aromatic and aliphatic amino acids.

  3. Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers.

    Science.gov (United States)

    Gwak, Hye Sun; Oh, Ik Sang; Chun, In Koo

    2004-02-01

    The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2+/-23.7 and 41.9+/-17.9 microg/cm2 per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.

  4. A novel validated RP-HPLC-DAD method for the simultaneous estimation of Metformin Hydrochloride and Canagliflozin in bulk and pharmaceutical tablet dosage form with forced degradation studies

    Directory of Open Access Journals (Sweden)

    Uttam Prasad Panigrahy

    2015-09-01

    Full Text Available A novel approach was used to develop and validate a rapid isocratic Reversed Phase-High Performance Liquid Chromatographic method for the simultaneous estimation of Metformin Hydrochloride and Canagliflozin in bulk and pharmaceutical tablet dosage form with forced degradation studies. The separation was performed by using Kromasil C18 column (250mm×4.6 mm, 5mm particle size, Waters Alliance e2695 HPLC system with 2998 PDA detector and mobile phase contained a mixture of 0.01M Ammonium acetate (pH adjusted to 3.5 with orthophosphoric acid and Acetonitrile (65:35, v/v. The flow rate was set to 1ml/min with responses measured at 254nm. The retention time of Metformin Hydrochloride and Canagliflozin was 2.440min and 3.713min respectively with resolution of 8.95.Linearity was established in the range of 50-300µg/ml for Metformin Hydrochloride and 5-30µg/ml for Canagliflozin with correlation coefficients (r2=0.999. The percentage recoveries were between (99.45%-100.65% and (99.95%-100.74% for Metformin Hydrochloride and Canagliflozin respectively. Validation parameters were evaluated according to the International Conference on Harmonization (ICH Q2 R1 guidelines. The forced degradation studies were performed by using HCl, NaOH, H2O2, thermal, UV radiation and water. Metformin Hydrochloride and Canagliflozin are more sensitive towards oxidative degradation condition. The developed method was successfully applied for the quantification and hyphenated instrumental analysis.

  5. A validated stability-indicating high performance liquid chromatographic method for moxifloxacin hydrochloride and ketorolac tromethamine eye drops and its application in pH dependent degradation kinetics

    Directory of Open Access Journals (Sweden)

    Jayant B Dave

    2013-01-01

    Full Text Available Background and Aim: A fixed dose combination of moxifloxacin hydrochloride and ketorolac tromethamine is used in ratio of 1:1 as eye drops for the treatment of the reduction of post operative inflammatory conditions of the eye. A simple, precise, and accurate High Performance Liquid Chromatographic (HPLC method was developed and validated for determination of moxifloxacin hydrochloride and ketorolac tromethamine in eye drops. Materials and Methods: Isocratic HPLC separation was achieved on a ACE C 18 column (C 18 (5 μm, 150 mm×4.6 mm, i.d. using the mobile phase 10 mM potassium di-hydrogen phosphate buffer pH 4.6-Acetonitrile (75:25 v/v at a flow rate of 1.0 mL/min. The detection was performed at 307 nm. Drugs were subjected to acid, alkali and neutral hydrolysis, oxidation and photo degradation. Moreover, the proposed HPLC method was utilized to investigate the pH dependent degradation kinetics of moxifloxacin hydrochloride and ketorolac tromethamine in buffer solutions at different pH values like 2.0, 6.8 and 9.0. Results and Conclusion: The retention time (t R of moxifloxacin hydrochloride and ketorolac tromethamine were 3.81±0.01 and 8.82±0.02 min, respectively. The method was linear in the concentration range of 2-20 μ/mL each for moxifloxacin hydrochloride and ketorolac tromethamine with a correlation coefficient of 0.9996 and 0.9999, respectively. The method was validated for linearity, precision, accuracy, robustness, specificity, limit of detection and limit of quantitation. The drugs could be effectively separated from different degradation products and hence the method can be used for stability analysis. Different kinetics parameters like apparent first-order rate constant, half-life and t 90 (time for 90% potency left were calculated.

  6. Development and validation of a rapid RP-UPLC method for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium from tablets

    Directory of Open Access Journals (Sweden)

    R Yanamandra

    2012-01-01

    Full Text Available A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8Ί. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations.

  7. HPLC法测定盐酸曲马多葡萄糖注射液中盐酸曲马多的含量%Determination of Tramadol Hydrochloride in tRAMADOL Hydrochloride Glucose Injections by HPLC

    Institute of Scientific and Technical Information of China (English)

    赵峰辉; 李新图; 陈建中; 陈跃; 汪变; 文桂芳

    2013-01-01

    目的:建立HPLC法测定盐酸曲马葡萄糖注射液中盐酸曲马多的含量.方法:色谱柱:Bondysil-C18(250 mm×4.6 mm,5 μm),流动相:醋酸-冰醋酸钠缓冲液(pH4.5)-甲醇(65:35),流速:1.0 ml·min-1,柱温:35℃,检测波长:271 nm,进样量:20 μl.结果:盐酸曲马多质量浓度线性范围为10~140μg·ml-1(r=0.999 0),平均回收率为99.9%(RSD=0.80%,n=9).结论:本方法简便、灵敏、准确.%Objective: To establish an HPLC method for the determination of tramadol hydrochloride in tramadol hydrochloride glucose injections. Method: The analysis was performed on a Bondysil-C18( 250 mm ×4.6 mm,5 μm )column. The mobile phase was acetic acid-sodium glacial acetic acid buffer ( pH 4.5) and methanol ( 65: 35 ). The flow rate was 1.0 ml · min-1, the column temperature was 30℃ , the detection wavelength was 271 nm, and the injection volume was 20 μl. Result: The linear range of tramadol hydrochloride was 10-140 μg · ml-1( r = 0.999 0 ), and the average recovery was 99.9% with RSD of 0.80%( n = 9 ). Conclusion: The method is simple, sensitive and accurate.

  8. Differential effect of buffering agents on the crystallization of gemcitabine hydrochloride in frozen solutions.

    Science.gov (United States)

    Patel, Mehulkumar; Munjal, Bhushan; Bansal, Arvind K

    2014-08-25

    The purpose of this study was to evaluate the differential effect of buffering agents on the crystallization of gemcitabine hydrochloride (GHCl) in frozen solutions. Four buffering agents, viz. citric acid (CA), malic acid (MA), succinic acid (SA) and tartaric acid (TA) were selected and their effect on GHCl crystallization was monitored using standard DSC and low temperature XRD. Onset of GHCl crystallization during heating run in DSC was measured to compare the differential effect of buffering agents. Glass transition temperature (Tg'), unfrozen water content in the freeze concentrate and crystallization propensity of the buffering agents was also determined for mechanistic understanding of the underlying effects. CA and MA inhibited while SA facilitated crystallization of GHCl even at 25 mM concentration. Increasing the concentration enhanced their effect. However, TA inhibited GHCl crystallization at concentrations crystallization could be explained by consideration of two opposing factors: (i) their own crystallization tendency and (ii) unfrozen water content in the freeze concentrate. In conclusion, it was established that API crystallization in frozen solution is affected by the type and concentration of the buffering agents.

  9. Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure.

    Science.gov (United States)

    Wojnarowska, Z; Swiety-Pospiech, A; Grzybowska, K; Hawelek, L; Paluch, M; Ngai, K L

    2012-04-28

    The pharmaceuticals, procaine hydrochloride and procainamide hydrochloride, are glass-forming as well as ionically conducting materials. We have made dielectric measurements at ambient and elevated pressures to characterize the dynamics of the ion conductivity relaxation in these pharmaceuticals, and calorimetric measurements for the structural relaxation. Perhaps due to their special chemical and physical structures, novel features are found in the ionic conductivity relaxation of these pharmaceuticals. Data of conductivity relaxation in most ionic conductors when represented by the electric loss modulus usually show a single resolved peak in the electric modulus loss M(")(f) spectra. However, in procaine hydrochloride and procainamide hydrochloride we find in addition another resolved loss peak at higher frequencies over a temperature range spanning across T(g). The situation is analogous to many non-ionic glass-formers showing the presence of the structural α-relaxation together with the Johari-Goldstein (JG) β-relaxation. Naturally the analogy leads us to name the slower and faster processes resolved in procaine hydrochloride and procainamide hydrochloride as the primary α-conductivity relaxation and the secondary β-conductivity relaxation, respectively. The analogy of the β-conductivity relaxation in procaine HCl and procainamide HCl with JG β-relaxation in non-ionic glass-formers goes further by the finding that the β-conductivity is strongly related to the α-conductivity relaxation at temperatures above and below T(g). At elevated pressure but compensated by raising temperature to maintain α-conductivity relaxation time constant, the data show invariance of the ratio between the β- and the α-conductivity relaxation times to changes of thermodynamic condition. This property indicates that the β-conductivity relaxation has fundamental importance and is indispensable as the precursor of the α-conductivity relaxation, analogous to the relation found

  10. Disposable screen-printed sensors for determination of duloxetine hydrochloride

    Directory of Open Access Journals (Sweden)

    Alarfaj Nawal A

    2012-01-01

    Full Text Available Abstract A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10-6-1.0 × 10-2 mol L-1 with detection limit reaching 5.0 × 10-7 mol L-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies.

  11. Linear scleroderma after contusion and injection of mepivacaine hydrochloride.

    Science.gov (United States)

    Ueda, Takashi; Niiyama, Shiro; Amoh, Yasuyuki; Katsuoka, Kensei

    2010-05-15

    A 36-year-old woman initially was treated for a contusion by local injection of mepivacaine hydrochloride into the left dorsum of the foot. Approximately 3 months after the injury and injection, linear sclerotic plaques originating from the site of contusion and injection were recognized. These progressed in extent and severity over a period of 3 years, when she presented to our clinic. By biopsy, swelling of collagen fibers in the lower dermis was revealed and the condition was diagnosed as linear scleroderma. Our present case had multiple linear sclerotic plaques of the left lower extremity, the distribution of which was consistent with Blaschko lines. It was also revealed that the initial sclerotic plaque was at the site of the contusion and local mepivacaine hydrochloride injection. Our present case is interesting in that the findings suggest a correlation between linear scleroderma plaque occurrence and the contusion or injection of mepivacaine.

  12. Influence of zoledronate on osteoclast differentiation and gene expression of calmodulin and calmodulin-dependent protein kinase Ⅱ%唑来膦酸对破骨细胞分化中钙调蛋白和钙调蛋白依赖性激酶Ⅱ基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    李鹏; 林珏杉; 张鹏; 董伟; 李金源; 戚孟春

    2013-01-01

    目的 研究唑来膦酸对破骨细胞分化及信号分子钙调蛋白、钙调蛋白依赖性激酶(calmodulin-dependent protein kinase,CAMK)Ⅱ基因表达的影响.方法 应用核因子κB受体激活蛋白配体(receptor activatior of nuclear factor κB ligand,RANKL)诱导小鼠单核巨噬细胞株RAW264.7向破骨细胞分化.细胞分为两组:A组用RANKL诱导5 d;B组在RANKL诱导3d后加用唑来膦酸处理2d.检测破骨细胞生成及钙调蛋白、CAMKⅡ基因表达情况.结果 B组新生多核破骨细胞、吸收陷窝数目及面积分别为(23±3)、(19±2)和(4951±223) μm2,均显著低于A组的(44±3)、(46±1)和(13 331±248) μm2 (P <0.01).与A组比较,B组钙调蛋白、CAMKⅡ基因表达也显著下降(P<0.01),mRNA及蛋白水平钙调蛋白分别下降了26.7%和37.2%;CAMKⅡ分别下降了57.0%和76.1%.结论 唑来膦酸可显著抑制破骨细胞生成和骨吸收功能,并下调钙调蛋白、CAMKⅡ基因表达;信号分子钙调蛋白、CAMKⅡ可能参与了唑来膦酸对破骨细胞的抑制作用.%Objective To investigate the effect of zoledronate acid on osteoclast differentiation and gene expression of calmodulin (CAM) and calmodulin-dependent protein kinase (CAMK) Ⅱ.Methods Receptor activatior of nuclear factor κB ligand (RANKL) was used to induce differentiation of RAW264.7cells into osteoclasts in vitro.The cells were divided into two groups,group A and group B.Both groups were treated with RANKL for 5 days,whereas group B was also treated with zoledronate for the last 2 days.Osteoclastogenesis and gene expression of CAM and CAMK Ⅱ were examined.Results In group B,the number of new-generated osteoclasts (≥ 3 nuclei),number and size of dentin resorption lacunaes were (23 ±3),(19 ±2) and (4951 ±223) μm2 respevtively,which were significantly lower than those [(44 ±3),(46±1) and (13 331 ±248) μ m2]in group A (P<0.01).mRNA and protein level of CAM and CAMK Ⅱ were also significantly

  13. OPTIMIZATION OF CONCENTRATION OF POLYHEXANIDE HYDROCHLORIDE IN MULTIPURPOSE SOLUTION.

    OpenAIRE

    Arora, A.; Ali, A.; M.T.Zzaman; Chauhan, S.; V.Handa

    2010-01-01

    There are a number of foreign pathogenic microorganisms like viruses, bacteria, yeast, fungi and protozoa which can inadvertently be introduced into eye via contact lens and hence disinfection is a vital part. Multifunctional solutions are generally intended to combine the action of cleaning disinfecting, rinsing lubricating deproteinising and soaking in one single product.In order to optimization of concentration of Polyhexanide hydrochloride in multipurpose solution some microbiological stu...

  14. FORMULATION AND EVALUATION OF FLOATING TABLETS OF TIZANIDINE HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Adimoolam Senthil

    2011-08-01

    Full Text Available The objective of the present investigation was to develop floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34–40% and short biological half life (4.2 h. Tizanidine hydrochloride floating tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropylmethylcellulose (HPMC K4M and K15M. Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility throughout the length of the gastrointestinal tract. Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in-vitro drug release characteristics in 12 hours. Drug release from floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there was no drug and excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. The optimized formulation (F9 released 75% of drug at the end of 10 hours by in-vitro release study.

  15. Clinical effect of venlafaxine combined with methylphenidate hydrochloride on narcolepsy

    Directory of Open Access Journals (Sweden)

    YAN Bin

    2013-11-01

    Full Text Available This study aims to explore the clinical effect of venlafaxine sustained-release capsules combined with methylphenidate hydrochloride tablets on narcolepsy. Thirty-eight cases of narcoleptic patients were randomly divided into venlafaxine combined with methylphenidate hydrochloride treatment group (observation group, N = 19 and methylphenidate hydrochloride and clomipramine treatment group (control group, N = 19. After a total of 12-week treatment, clinical curative effect and adverse drug reactions were observed in 2 groups of patients. The results showed that effective rate of the treatment for excessive daytime sleepiness (EDS in observation group was higher than that of the control group (15/19 vs 8/19, P = 0.044, and effective rate of the treatment for cataplexy in observation group was higher than that of the control group (13/19 vs 6/19, P = 0.048. The rate of adverse drug reactions in observation group was lower than that in the control group (χ2 = 8.889, P = 0.003. It was indicated that venlafaxine combined with methylphenidate had good curative effect on narcolepsy with EDS and cataplexy symptoms.

  16. Mucoadhesive microspheres of propranolol hydrochloride for nasal delivery

    Directory of Open Access Journals (Sweden)

    Dandagi P

    2007-01-01

    Full Text Available Gelatin A microspheres of propranolol hydrochloride for intranasal systemic delivery were developed with the aim to avoid first pass metabolism, to improve the patient compliance, to use an alternative therapy to conventional dosage form, to achieve controlled blood level profiles, and to improve the therapeutic efficacy of propranolol hydrochloride in the treatment of various cardiovascular disorders and as a prophylactic for migraine. Gelatin A microspheres were prepared by emulsion crosslinking method using glutaradehyde as a crosslinking agent. Gelatin and chitosan were used as polymer and co polymer respectively. All the prepared microspheres were evaluated for physical characteristics, such as particle size, incorporation efficiency, swelling index, in vitro bioadhesion using rat jejunum and in vitro drug release in pH 6.6 phosphate buffer. Average particle size of microspheres was found to be in the size range 1-50 mm. Increase in drug and polymer concentration in the formulation increased incorporation efficiency. All the microsphers showed good bioadhesive properties and swelling indices and good sustained release of drug. The data indicates that propranolol hydrochloride release followed Higuchi′s matrix and Peppa′s model. Stability studies showed stability of formulation at all the conditions to which they were subjected.

  17. A novel kind of TSV slurry with guanidine hydrochloride

    Science.gov (United States)

    Jiao, Hong; Yuling, Liu; Baoguo, Zhang; Xinhuan, Niu; Liying, Han

    2015-10-01

    The effect of a novel alkaline TSV (through-silicon-via) slurry with guanidine hydrochloride (GH) on CMP (chemical mechanical polishing) was investigated. The novel alkaline TSV slurry was free of any inhibitors. During the polishing process, the guanidine hydrochloride serves as an effective surface-complexing agent for TSV CMP applications, the removal rate of barrier (Ti) can be chemically controlled through tuned selectivity with respect to the removal rate of copper and dielectric, which is helpful to modifying the dishing and gaining an excellent topography performance in TSV manufacturing. In this paper, we mainly studied the working mechanism of the components of slurry and the skillful application guanidine hydrochloride in the TSV slurry. Project supported by the Major National Science and Technology Special Projects (No. 2009ZX02308), the Fund Project of Hebei Provincial Department of Education, China (No. QN2014208), the Natural Science Foundation of Hebei Province, China (No. E2013202247), and Colleges and Universities Scientific research project of Hebei Province, China (No. Z2014088).

  18. Spectrophotometric estimation of betahistine hydrochloride in tablet formulations

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2010-01-01

    Full Text Available Aim: The study aims to develop simple, sensitive, rapid, accurate and precise spectrophotometric method for estimation of Betahistine hydrochloride in tablet dosage forms. Materials and Methods: For method I and II, in a series of 10 ml volumetric flask, aliquots of standard drug solution (100 μg/ml in double distilled water were transferred and diluted with same so as to give several dilutions in concentration range of 15-90 μg/ml and 10-80 μg/ml respectively of betahistine hydrochloride. To 5 ml of each dilution taken in a separating funnel, (5 ml of methyl orange for method I and 5 ml of bromo phenol blue for method II reagent and 5 ml of chloroform was added. Reaction mixture was shaken gently for 5 min and allowed to stand so as to separate aqueous and chloroform layer. Absorbance maxima measured at 421.6 nm and 412 nm for method I and II respectively. Results: The recovery studies were found close to 100 % that indicates accuracy and precision of the proposed methods. The statistical analysis was carried out and results of which were found satisfactory. Standard deviation values were found low that indicated reproducibility of the proposed methods. Conclusion: Based on results the developed methods could be used for routine estimation of betahistine hydrochloride from tablet formulations.

  19. Preparation and Characterization of Chitosan Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    FENG; HuiXia

    2001-01-01

    Chitin 1 is a biodegradable and nontoxic polysaccharide widely spread among marine and terrestrial invertebrates and fungi. It is usually obtained from waste materials of the sea food-processing industry, mainly shells of crab, shrimp, prawn and krill. Native chitin occurs in such natural composite materials usually combined with inorganics, proteins, lipids and pigments. Its isolation calls for chemical treatments to eliminate these contaminants, some of which maybe coimmercially explored. By treating crude chitin with aqueous 40~50% sodium hydroxide at 110~115℃ chitosan is obtained. However, the fully deacetylated product is rarely obtained due to the risks of side reactions and chain deplolymerization. Chitosan and chitin are closely related since both are linear polysaccharides containing 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose units joined by β (1→4) glycosidic bonds. They can be distinguished by their contents of the above-mentioned units and by their solubilities in aqueous media. The acetylated units predominate in chitin while chitosan chains contain mostly deacetylated units. Chitin is soluble in a very limited number of solvents while chitosan is soluble in aqueous dilute solutions of a number of mineral and organic acids, being the most common ones, the hydrochloric and acetic acids. In aqueous dilute acid media chitosan forms salts, producing polyelectrolyte chains bearing positive charges on the nitrogen atoms of their amine groups. In fact the salt of chitosan may be formed in a separate step or as a consequence of the presence of acid in the water suspension of the neutralized form of chitosan.  ……

  20. Preparation and Characterization of Chitosan Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Chitin 1 is a biodegradable and nontoxic polysaccharide widely spread among marine and terrestrial invertebrates and fungi. It is usually obtained from waste materials of the sea food-processing industry, mainly shells of crab, shrimp, prawn and krill. Native chitin occurs in such natural composite materials usually combined with inorganics, proteins, lipids and pigments. Its isolation calls for chemical treatments to eliminate these contaminants, some of which maybe coimmercially explored. By treating crude chitin with aqueous 40~50% sodium hydroxide at 110~115℃ chitosan is obtained. However, the fully deacetylated product is rarely obtained due to the risks of side reactions and chain deplolymerization. Chitosan and chitin are closely related since both are linear polysaccharides containing 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose units joined by β (1→4) glycosidic bonds. They can be distinguished by their contents of the above-mentioned units and by their solubilities in aqueous media. The acetylated units predominate in chitin while chitosan chains contain mostly deacetylated units. Chitin is soluble in a very limited number of solvents while chitosan is soluble in aqueous dilute solutions of a number of mineral and organic acids, being the most common ones, the hydrochloric and acetic acids. In aqueous dilute acid media chitosan forms salts, producing polyelectrolyte chains bearing positive charges on the nitrogen atoms of their amine groups. In fact the salt of chitosan may be formed in a separate step or as a consequence of the presence of acid in the water suspension of the neutralized form of chitosan.

  1. Use of xylazine hydrochloride-ketamine hydrochloride for immobilization of wild leopards (Panthera pardus fusca) in emergency situations.

    Science.gov (United States)

    Belsare, Aniruddha V; Athreya, Vidya R

    2010-06-01

    In India, leopards (Panthera pardus fusca) inhabit human-dominated landscapes, resulting in encounters that require interventions to prevent harm to people, as well as the leopards. Immobilization is a prerequisite for any such intervention. Such emergency field immobilizations have to be carried out with limited tools, often amidst large uncontrollable crowds. An effective and practicable approach is discussed, based on 55 wild leopard immobilizations undertaken between January 2003 and April 2008. A xylazine hydrochloride (1.4 +/- 0.3 mg/kg)--ketamine hydrochloride (5 +/- 2 mg/kg) mixture was used for immobilization of leopards, based on estimated body weight. When weight could not be estimated, a standard initial dose of 50 mg of xylazine--150 mg of ketamine was used. Supplemental doses (50-75 mg) of only ketamine were used as required. No life-threatening adverse effects of immobilization were documented for at least 1 mo postimmobilization.

  2. A Validated Stability-indicating Reverse Phase HPLC Assay Method for the Determination of Memantine Hydrochloride Drug Substance with UV-Detection Using Precolumn Derivatization Technique

    Directory of Open Access Journals (Sweden)

    Bhavil Narola

    2010-07-01

    Full Text Available This present paper deals with the development and validation of a stability indicating high performance liquid chromatographic method for the quantitative determination of Memantine hydrochloride. Memantine hydrochloride was derivatized with 0.015 M 9-fluorenylmethyl chloroformate (FMOC and 0.5 M borate buffer solution by keeping it at room temperature for about 20 minutes and the chromatographic separation achieved by injecting 10 µL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a kromasil C18 column (150 × 4.6 mm, 5 µ. The mobile phase consisting of 80% acetonitrile and 20% phosphate buffer solution and a flow rate of 2 milliliter/minute. The Memantine was eluted at approximately 7.5 minutes. The volume of FMOC used in derivatization, concentration of FMOC and derivatization time was optimized and used. Forced degradation studies were performed on bulk sample of Memantine hydrochloride using acid (5.0 Normal (N hydrochloric acid, base (1.0 N sodium hydroxide, oxidation (30% hydrogen peroxide, thermal (105°C, photolytic and humidity conditions. The developed LC method was validated with respect to specificity, precision (% RSD about 0.70%, linearity (linearity of range about 70–130 µg/mL, ruggedness (Overall % RSD about 0.35%, stability in analytical solution (Cumulative % RSD about 0.11% after 1450 min. and robustness.

  3. Synthesis of silver nanoparticles in the presence of diethylaminoethyl-dextran hydrochloride polymer and their SERS activity

    Science.gov (United States)

    Mikac, L.; Jurkin, T.; Štefanić, G.; Ivanda, Mile; Gotić, Marijan

    2017-09-01

    The silver nanoparticles (AgNPs) were synthesized upon γ-irradiation of AgNO3 precursor suspensions in the presence of diethylaminoethyl-dextran hydrochloride (DEAE-dextran) cationic polymer as a stabilizer. The dose rate of γ-irradiation was 32 kGy h-1, and absorbed doses were 30 and 60 kGy. The γ-irradiation of the precursor suspension at acidic or neutral pH conditions produced predominantly the silver(I) chloride (AgCl) particles, because of the poor solubility of AgCl already present in the precursor suspension. The origin of AgCl in the precursor suspension was due to the presence of chloride ions in DEAE-dextran hydrochloride polymer. The addition of ammonia to the precursor suspension dissolved the AgCl precipitate, and the γ-irradiation of such colourless suspension at alkali pH produced a stable aqueous suspension with rather uniform spherical AgNPs of approximately 30 nm in size. The size of AgNPs was controlled by varying the AgNO3/DEAE-dextran concentration in the suspensions. The surface-enhanced Raman scattering (SERS) activities of synthesized AgNPs were examined using organic molecules rhodamine 6G, pyridine and 4-mercaptobenzoic acid (4-MBA). The NaBH4 was used as SERS aggregation agent. The SERS results have shown that in the presence of synthesized AgNPs, it was possible to detect low concentration of tested compounds.

  4. Floating matrix dosage form for propranolol hydrochloride based on gas formation technique: development and in vitro evaluation.

    Science.gov (United States)

    Chaturvedi, Kiran; Umadevi, S; Vaghani, Subhash

    2010-01-01

    Gastroretentive tablets of propranolol hydrochloride were developed by direct compression method using citric acid and sodium bicarbonate as the effervescent base. Hydroxypropyl methylcellulose; HPMC K15M was used to prepare the floating tablets to retard the drug release for 12h in stomach. Na-carboxymethyl cellulose (NaCMC) or carbopol 934P was added to alter the drug release profile or the dimensional stability of the formulation. Dicalcium phosphate (DCP) was used as filler. Formulations were evaluated for floating lag time, duration of floating, dimensional stability, drug content and in vitro drug release profile. The formulations were found to have floating lag time less than 1min. It was found that the dimensional stability of the formulations increase with increasing concentration of the swelling agent. The release mechanism of propranolol hydrochloride from floating tablets was evaluated on the basis of Peppas and Higuchi model. The ânâ value of the formulations ranged from 0.5201 to 0.7367 (0.5DCP, 3.75% citric acid and 18.75% sodium bicarbonate seemed most desirable. FTIR, DSC and XRPD studies indicated the absence of any significant chemical interaction within dug and excipients. Stability study of optimized formulation revealed no significant change and found to be stable.

  5. Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic.

    Science.gov (United States)

    Au, Kin Man; Satterlee, Andrew; Min, Yuanzeng; Tian, Xi; Kim, Young Seok; Caster, Joseph M; Zhang, Longzhen; Zhang, Tian; Huang, Leaf; Wang, Andrew Z

    2016-03-01

    Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of this novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80-85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis.

  6. A Novel, Rapid, and Validated Stability-Indicating UPLC Method for the Estimation of Drotaverine Hydrochloride and Ibuprofen Impurities in Oral Solid Dosage Form.

    Science.gov (United States)

    Vijay Kumar, Rekulapally; Rao, Vinay U; Anil Kumar, N; Venkata Subbaiah, B

    2015-01-01

    A novel, stability-indicating, reversed-phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of pure drotaverine hydrochloride and ibuprofen in the presence of their impurities and degradation products. The method was developed using a Waters UPLC BEH C18, 100 × 2.1 mm, 1.7 µm column with a flow rate of 0.3 mL/min and detector wavelength at 210 nm. The mobile phase consisted of potassium dihydrogen orthophosphate buffer and acetonitrile. Drotaverine hydrochloride and ibuprofen were subjected to the stress conditions of oxidative, acid, base, photolytic, and thermal degradation. Degradation products resulting from the stress studies were well-resolved, thus confirming the test method as stability-indicating. Validation of the method was carried out as per International Conference on Harmonization guidelines.

  7. Synthesis and activity of (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride: a prodrug form of (R)-(-)-phenylephrine.

    Science.gov (United States)

    Yuan, S S; Bador, N

    1976-06-01

    Optically pure (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride was synthesized by the following sequence: (R)-(-)-phenylephrine was condensed with acetone in the presence of calcium carbide to give an oxazolidine derivative and then treated with thallous ethoxide in ether followed by trimethylacetyl chloride to yield the phenolic ester. Finally, the oxazolidine ring was cleaved by one equivalent of hydrogen chloride in ethanol. Condensation of phenylephrine with benzaldehyde, with or without solvents, gave either 1,1,2-trimethyl-4,6-dihydroxy-1,2,3,4-tetrahydroisoquinoline or a mixture of side-chain oxazolidine and the tetrahydroisoquinoline. Condensation of epinephrine with opianic acid in pyridine also gave a tetrahydroisoquinoline only. When applied on rabbit eyes, the prodrug (R)-(-)-m-trimethylacetoxy-alpha[(methylamino)methyl]benzyl alcohol hydrochloride exhibited an unexpected, three times higher mydriatic activity than the corresponding racemic prodrug and was 15 times more active than the parent, (R)-(-)-phenylephrine.

  8. High-performance liquid chromatographic determination of memantine hydrochloride in rat plasma using sensitive fluorometric derivatization.

    Science.gov (United States)

    Xie, Mei-Fen; Zhou, Wei; Tong, Xin-Yi; Chen, Yi-Le; Cai, Yi; Li, Yan; Duan, Geng-Li

    2011-02-01

    In this study, we investigated a simple, sensitive and reliable liquid chromatography-fluorescence detection method for the determination of memantine hydrochloride in rat plasma which was based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). For the first time, FMOC-Cl was introduced into derivatization of memantine hydrochloride in rat plasma. The amino groups of memantine hydrochloride and amantadine hydrochloride (internal standard) were trapped with FMOC-Cl to form memantine hydrochloride-FMOC-Cl and amantadine hydrochloride-FMOC-Cl compositions, which can be very compatible for LC-FLD. Precipitation of plasma proteins by acetonitrile was followed by vortex mixing and centrifugation. Chromatographic separation was performed on a C(18) column (DIAMONSIL 150 × 4.6 mm, id 5 μm) with a mobile phase consisting of acetonitrile and water at a flow rate of 1.0 mL/min. The retention times of memantine hydrochloride-FMOC-Cl and amantadine hydrochloride-FMOC-Cl compositions were 23.69 and 40.27 min, respectively. Optimal conditions for the derivatization of memantine hydrochloride were also described. The limit of quantification (LOQ) was 25 ng/mL for memantine hydrochloride in plasma, the linear range was 0.025-5.0 μg/mL in plasma with a correlation coefficient (r) of 0.9999. The relative standard deviations (RSDs) of intra-day and inter-day assays were 4.46-12.19 and 5.23-11.50%, respectively. The validated method was successfully applied to the determination of memantine hydrochloride in rat plasma samples.

  9. Stability-indicating high performance thin layer chromatography determination of Paroxetine hydrochloride in bulk drug and pharmaceutical formulations.

    Science.gov (United States)

    Venkatachalam, A; Chatterjee, Vidya S

    2007-08-29

    A simple selective precise and stability-indicating high performance thin layer chromatographic method of analysis of Paroxetine hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed TLC (Thin Layer Chromatography) aluminum precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of butanol:acetic acid:water (8:2:0.5, v/v/v). This system was found to give compact spots for Paroxetine HCl (Rf, retardation factor, value-0.48+/-0.02). Paroxteine HCl was subjected to acid and alkali hydrolysis, oxidation and photodegradation, where the degraded product was well separated from the pure drug. Densitometric analysis of Paroxetine hydrochloride was carried out in the absorbance mode at 295 nm. The linear regression analysis data for the calibration spots showed good relationship with (regression) r2 = 0.9903 in the amount range of 300-1500 ng (nanogram) per spot. The mean value of co-relation co-efficient, slope and intercept were 0.9903+/-0.001, 5.38+/-0.058 and 182.5+/-2.16 respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 50 and 150 ng, respectively. The drug does not undergo degradation with oxidation, but gets affected in acidic and alkaline conditions. The acid and alkali degradation showed extra peaks at 0.4 and 0.08 Rf, respectively. This indicates that the drug is susceptible to acidic and alkaline medium. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one.

  10. Stability Indicating HPLC Method for Estimation of S-amlodipine besylate and Nebivolol hydrochloride in Bulk Drugs and Marketed Formulation

    Directory of Open Access Journals (Sweden)

    G.V.S Kumar

    2012-10-01

    Full Text Available A simple, precise and stability indicating reversed phase liquid chromatographic method was developed and validated for estimation of s-amlodipine besylate and nebivolol hydrochloride in bulk drug and marketed formulation. The separation was achieved on Zorbax C8 G (250mm x 4.6mm, 5µm analytical column with mobile phase comprising of 0.05M Potassium di hydrogen phosphate: Acetonitrile (pH 3.0 (60:40v/v at isocratic flow of 1.0ml/min with UV detection at 269 nm. The retention times of s-amlodipine besylate and nebivolol hydrochloride was found to be 5.2 and 6.8 minutes respectively. The method was successfully validated in accordance to ICH guidelines for accuracy, precision, specificity, linearity, ruggedness and robustness. The linear regression analysis data for calibration plots showed good linear relationship in the concentration range 0.125-0.375μg/mL for s-amlodipine besylate and 0.25-0.75 for nebivolol hydrochloride. The drugs were exposed to acidic, basic, oxidation, thermal and photolytic stress degradation conditions. The resultant stressed samples were analyzed by the proposed method and was established to provide high resolution among the degradation products and the analytes. All the peaks of degraded product were resolved from the active pharmaceutical ingredient with significantly different retention time and the peak purity of analyte peaks in the stressed samples was confirmed by photodiode array detector. The method could effectively separate the drug from its degradation product; it can be employed as a stability- indicating one.

  11. 78 FR 27971 - Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not...

    Science.gov (United States)

    2013-05-13

    ... HUMAN SERVICES Food and Drug Administration Determination That REV-EYES (Dapiprazole Hydrochloride... determined that REV-EYES (dapiprazole hydrochloride ophthalmic solution), 0.5%, was not withdrawn from sale... refer to a listed drug. REV-EYES (dapiprazole hydrochloride ophthalmic solution), 0.5%, is the...

  12. 21 CFR 524.1484d - Neomycin sulfate, hydrocortisone acetate, tetracaine hydrochloride ear ointment.

    Science.gov (United States)

    2010-04-01

    ..., tetracaine hydrochloride ear ointment. 524.1484d Section 524.1484d Food and Drugs FOOD AND DRUG..., tetracaine hydrochloride ear ointment. (a) Specifications. The product contains 5 milligrams of neomycin... a lesser degree, chronic otitis externa in dogs and cats. In treatment of ear canker and...

  13. 21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride tablet or oblet (bolus). 520.1242b Section 520.1242b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242b Levamisole hydrochloride tablet...

  14. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride and piperazine dihydrochloride. 520.1242c Section 520.1242c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242c Levamisole hydrochloride...

  15. Effects of metomindate hydrochloride and tricaine methanesulfonate on the short term cortisol response in channel catfish

    Science.gov (United States)

    The effects of metomidate hydrochloride and tricaine methanesulfonate (MS-222) on cortisol stress response of channel catfish, Ictalurus punctatus, were examined during 10 minutes of sedation. Channel catfish were assigned to three treatments: 1. Metomidate hydrochloride (12.5 mg/L), 2. MS-222 (100...

  16. A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A convenient approach for the preparation of sarpogrelate hydrochloride was developed.Two series of sarpogrelate hydrochloride analogues were designed and synthesized in order to improve their platelet aggregation inhibitory activities, biological tests suggested that these compounds have platelet aggregation inhibitory activities to some extent.

  17. 40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

    Science.gov (United States)

    2010-07-01

    ... Insulation Resins by Hydroxylamine Hydrochloride B Appendix B to Subpart NNN of Part 63 Protection of...—Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride 1. Scope This method was specifically developed for water-soluble phenolic resins that have a relatively high free-formaldehyde...

  18. HPLC法测定鼻炎糖浆中盐酸麻黄碱和盐酸伪麻黄碱的含量%Determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Biyan Syrup by HPLC

    Institute of Scientific and Technical Information of China (English)

    冉亚东; 原欢欢; 官柳

    2014-01-01

    目的:建立高效液相色谱法测定鼻炎糖浆中盐酸麻黄碱和盐酸伪麻黄碱含量的测定方法。方法采用Agilent Zorbax SB-C18色谱柱(4.6 mm ×250 mm,5μm),乙腈-0.2%磷酸溶液(含0.2%三乙胺)(2:98)为流动相,流速:1.0 mL ·min-1,检测波长206 nm,柱温:25℃。结果盐酸麻黄碱进样量在0.124~1.86μg范围内与峰面积呈良好线性(r=0.9999),平均回收率为99.99%,RSD=1.24%(n=6);盐酸伪麻黄碱进样量在0.1038~1.557μg范围内与峰面积呈良好线性(r=0.9999),平均回收率为99.33%,RSD=1.93%(n=6)。结论该方法准确、重复性好,可用于鼻炎糖浆中盐酸麻黄碱和盐酸伪麻黄碱的测定。%Objective To establish an HPLC method for the determination of ephedrine hydrochloride and pseudo-ephedrine hydrochloride in Biyan Syrup. Methods The Agilent Zorbax SB-C18(4. 6 mm × 250 mm,5 μm)column was used. The mobile phase consisted of acetonitrile-0. 20% phosphoric acid(containing 0. 2% triethylamine)(2:98)with the flow rate of 1. 0 mL·min-1 . The detection wavelength was 206 nm and the column temperature was 25 ℃. Results The linear range of ephedrine hydrochloride and pseudoephedrine hydrochloride was 0. 124~1. 86μg(r=0. 999 9)and 0. 103 8~1. 557 μg(r=0. 999 9)with the average recovery of 99. 99%(RSD=1. 24%,n=6)and 99. 33%(RSD=1. 93%,n=6),respectively. Conclusion The method was accurate and reproducible. It can be used for the determination of ephed-rine hydrochloride and pseudoephedrine hydrochloride in Biyan Syrup.

  19. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-01-01

    Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  20. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride:P300 event related potential

    Institute of Scientific and Technical Information of China (English)

    Qiang Liu; Xiu-juan Wang; Zhe-cheng Zhang; Rong Xue; Ping Li; Bo Li

    2016-01-01

    Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days), or combined with acupuncture atShenting (DU24),Tianzhu (BL10),Sishencong (Extra), Yintang (Extra),Renzhong (DU26),Neiguan (PC6),Shenmen (HT7),Fengchi (GB20),Wangu (GB12) andBaihui (DU20) (once a day for 56 days). Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased ampli-tude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identiifed within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These ifndings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  1. Liquid Chromatographic Methods for the Determination of Vildagliptin in the Presence of its Synthetic Intermediate and the Simultaneous Determination of Pioglitazone Hydrochloride and Metformin Hydrochloride

    OpenAIRE

    El-Bagary, Ramzia I.; Elkady, Ehab F.; Ayoub, Bassam M.

    2011-01-01

    Two reversed-phase liquid chromatographic (RP-LC) methods are described for the determination of two binary mixtures of hypoglycemic agents. In the first method, vildagliptin (VDG) was determined in the presence of 3-amino-1-adamantanol (AAD), a synthetic intermediate and impurity of VDG. In the second method, pioglitazone hydrochloride (PGZ) and metformin hydrochloride (MET) were simultaneously determined in their binary mixture. Chromatographic separation in the two methods was achieved on ...

  2. Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation.

    Science.gov (United States)

    Yang, Zhenlei; Liu, Junli; Gao, Jinhua; Chen, Shilei; Huang, Guihua

    2015-11-10

    The present work evaluated the feasibility of chitosan coated liposomes (c-Lips) for the intravenous delivery of vancomycin hydrochloride (VANH), a water-soluble antibiotic for the treatment of gram-positive bacterial infections like osteomyelitis, arthritis, endocarditis, pneumonia, etc. The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects especially nephrotoxicity. Firstly, the vancomycin hydrochloride liposomes (VANH-Lips) were prepared by modified reverse phase evaporation method, then the chitosan wrapped vancomycin hydrochloride liposomes (c-VANH-Lips) nanosuspension was formulated by the method of electrostatic deposition. Based on the optimized results of single-factor screening experiment, the c-VANH-Lips were found to be relatively uniform in size (220.40 ± 3.56 nm) with a narrow polydispersity index (PI) (0.21 ± 0.03) and a positive zeta potential (25.7 ± 1.12 mV). The average drug entrapment efficiency (EE) and drug loading (DL) were 32.65 ± 0.59% and 2.18 ± 0.04%, respectively. The in vitro release profile of c-VANH-Lips possessed a sustained release Characterization and the release behavior was in accordance with the Weibull equation. Hemolysis experiments showed that its intravenous injection had preliminary safety. In vivo, after intravenous injection to mice, c-VANH-Lips showed a longer retention time and higher AUC values compared with the VANH injection (VANH-Inj) and VANH-Lips. In addition, biodistribution results clearly demonstrated that c-VANH-Lips preferentially decreased the drug distribution in kidney of mice after intravenous injection. These results revealed that injectable c-VANH-Lips may serve as a promising carrier for VANH to increase therapeutic efficacy on gram-positive bacterial infections and reduce nephrotoxicity, which provides significantly clinical value for long-term use of VANH.

  3. Multicomposite ultrathin capsules for sustained ocular delivery of ciprofloxacin hydrochloride.

    Science.gov (United States)

    Bhadra, Dipankar; Gupta, Girish; Bhadra, Sulekha; Umamaheshwari, R B; Jain, Narendra

    2004-07-16

    The present work is intended to develop a sustained bioadhesive drug delivery system for delivery of Ciprofloxacin Hydrochloride in Cul-de-Sac for sustained and effective antimicrobial chemotherapy. For this, ultrathin multicomposite capsular systems were selected. Multicomposite ultrathin capsules are molecular assemblies of tailored architecture having layer-by-layer adsorption of oppositely charged macromolecules onto colloidal particles. In the present study colloidal calcium phosphate core and gluateraldehyde fixed RBCs were used as core on which alginate (-vely charged) and polyallylamine hydrochloride (+vely charged) polyelectrolyte coating was deposited alternatively upto 10th layer. The coating in each subsequent layer was determined by changes in zeta potential. Ciprofloxacin hydrochloride was loaded in the capsules by incubation with the capsules suspended in phosphate buffer saline pH 7.4. The cores of the capsules were then removed by treatment with 0.1N HCl for calcium phosphate core and by sodium hypochlorite for RBC cored capsules. The hollow ciprofloxacin HCl loaded capsules were the evaluated in-vitro for pattern of layer-by-layer drug loading, drug release, stability at various temperatures and ionic concentrations and corneal retention. The core removal process was found to have minimal effects on drug loading in capsules. The drug loading was found to be higher for RBC cored hollow capsules and hence release rate was lower as compared to calcium cored hollow capsules. Draize test for corneal irritancy proved that the capsules were not irritating. The capsules were found to deliver the ciprofloxacin in cul-de-sac of rabbit's eyes for prolonged period. Based on corneal retention studies and tear drug concentration, the capsules can be considered for suitable and safe use for sustained ocular delivery of drugs.

  4. Indirect Electrochemical Oxidation of 4-Amino-dimethyl-aniline Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The indirect electrochemical oxidation of 4-amino-dimethyl-aniline hydrochloride containing wastewater generated from vanillin production is presented. Experiments were conducted at a constant current density of 30 mA/cm2 via a Ti/Ru-Ti-Sn ternary oxide coated anode and an undivided reactor. During the various stages of the electrolysis, parameters such as the values of chemical oxygen demand (COD) and total organic carbon (TOC) were determined in order to evaluate the feasibility of the electrochemical treatment. The energy consumption and the current efficiency during the electrolysis were calculated. The present study proves the effectiveness of the electrochemical treatment for wastewater resulted from vanillin production.

  5. Verapamil hydrochloride release characteristics from new copolymer zwitterionic matrix tablets.

    Science.gov (United States)

    Kostova, Bistra; Kamenska, Elena; Ivanov, Ivo; Momekov, George; Rachev, Dimitar; Georgiev, George

    2008-01-01

    The aim of this study was to synthesize stable copolymer (vinyl acetate-co-3-dimethyl[methacryloyloxyethyl] ammonium propane sulfinate) zwitterionic latex with different compositions for the first time by emulsifier-free emulsion copolymerization. Throughout the course of the study, a proposal was made for the explanation of the relationship between the "overshooting" phenomenon (a swelling kinetics with a maximum) and the specific self-association of the zwitterionic copolymers. The zwitterionic monomer unit mole fraction, pH, and ionic strength effects on this relationship, on the swelling kinetics of the zwitterionic copolymers, and on the sustained verapamil hydrochloride release from the model tablets were established by the study's authors.

  6. Biodegradation of drotaverine hydrochloride by free and immobilized cells of Rhodococcus rhodochrous IEGM 608.

    Science.gov (United States)

    Ivshina, I B; Vikhareva, E V; Richkova, M I; Mukhutdinova, A N; Karpenko, Ju N

    2012-10-01

    Drotaverine [1-(3,4-diethoxybenzylidene)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinoline] hydrochloride, an antispasmodic drug derived from benzylisoquinoline was evaluated for its biodegradability using a bacterial strain Rhodococcus rhodochrous IEGM 608. The experiments were performed under aerobic conditions with rhodococci cultures able to degrade drotaverine. In the presence of glucose, the removal efficiency of drotaverine by free Rhodoccocus cells pre-grown with isoquinoline was above 80 % (200 mg/l, initial concentration) after 25 days. Rhodococcus immobilization on hydrophobized sawdust enhanced the biodegradation process, with the most marked drotaverine loss being observed during the first 5 days of fermentation. High metabolic activity of rhodococcal cells towards drotaverine was confirmed respirometrically. GC-MS analysis of transformation products resulting from drotaverine biodegradation revealed 3,4-diethoxybenzoic acid, 3,4-diethoxybenzaldehyde and 3,4-diethoxybenzoic acid ethyl ester which were detected in the culture medium until drotaverine completely disappeared. Based on these major and other minor metabolites, putative pathways for drotaverine biodegradation were proposed. The obtained data broadened the spectrum of organic xenobiotics oxidized by Rhodoccocus bacteria and proved their potential in decontamination of natural ecosystems from pharma pollutants.

  7. Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients.

    Science.gov (United States)

    Filiopoulos, Vassilis; Koutis, Ioannis; Trompouki, Sofia; Hadjiyannakos, Dimitrios; Lazarou, Dimitrios; Vlassopoulos, Dimosthenis

    2011-02-01

    Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance.

  8. Stability of polymorphic forms of ranitidine hydrochloride.

    Science.gov (United States)

    Wu, V; Rades, T; Saville, D J

    2000-07-01

    , resulted in a preferential loss of form II (compared to form I). Loss was greater at 30 degrees C/75% RH than at 20 degrees C/75% RH. Form II was also preferentially lost under low humidity conditions created by a saturated solution of potassium carbonate (45% RH) at the elevated temperature of 42 degrees C. This environment was shown to be acidic.

  9. RP-HPLC analytical method development and optimization for quantification of donepezil hydrochloride in orally disintegrating tablet.

    Science.gov (United States)

    Liew, Kai Bin; Peh, Kok Khiang; Fung Tan, Yvonne Tze

    2013-09-01

    An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.

  10. Analgesic effects of meloxicam, morphine sulfate, flunixin meglumine, and xylazine hydrochloride in African-clawed frogs (Xenopus laevis).

    Science.gov (United States)

    Coble, Dondrae J; Taylor, Douglas K; Mook, Deborah M

    2011-05-01

    We evaluated analgesic use and analgesiometry in aquatic African-clawed frogs (Xenopus laevis). We used the acetic acid test (AAT) to assess the analgesic potential of systemic xylazine hydrochloride, meloxicam, flunixin meglumine, and morphine sulfate after injection into the dorsal lymph sac. Flunixin meglumine provided better analgesia than did the other drugs, most evident at 5 and 9 h after administration. Because the AAT was associated with the development of dermal lesions, we discontinued use of this assay and chose the Hargreaves test as an alternative method of measuring nociception in Xenopus. This assay is commonly performed in rodents, but its efficacy in an aquatic species such as Xenopus was unknown prior to this study. We found that the Hargreaves test was an effective measure of nociception in Xenopus, and we used it to evaluate the effectiveness of the nonopiod agents xylazine hydrochloride, meloxicam, and flunixin meglumine both in the absence of surgery and after surgical oocyte harvest. Similar to findings from the AAT, flunixin meglumine provided better analgesia in the Hargreaves test than did the other agents when analyzed in the absence of surgical intervention. Results were equivocal after oocyte harvest. Although surgical oocyte harvest is a common procedure in Xenopus, and currently there are no published recommendations for analgesia after this invasive surgery. Future studies are needed to clarify the efficacy of nonsteroidal antiinflammatory drugs for that purpose.

  11. Fluorescence studies of the effect of pH, guanidine hydrochloride and urea on equinatoxin II conformation.

    Science.gov (United States)

    Malavasic, M; Poklar, N; Macek, P; Vesnaver, G

    1996-04-01

    The solvent denaturation of equinatoxin II (EqTxII) in aqueous solutions of urea, guanidine hydrochloride (Gu-HCl) and at various pH values was examined by monitoring changes in the protein intrinsic emission fluorescence spectra and in the fluorescence spectra of the added external probe ANS. It has been observed that EqTxII denaturation is reflected in a strong red shift of intrinsic fluorescence emission maxima accompanied by a simultaneous decrease in fluorescence intensity and that guanidine hydrochloride is significantly more powerful denaturant than urea or changing of pH. Comparison of intrinsic fluorescence spectra of EqTxII denatured by one of the three denaturing agents has shown that the fully denatured states of the protein in Gu-HCl and urea are similar and substantially different from those induced by changing of pH. Furthermore, according to the measurements of the ANS-fluorescence in EqTxII solutions as a function of pH the protein exists at pH values below 2.0 in an acid-denatured compact state.

  12. Determination of losartan potassium, quinapril hydrochloride and hydrochlorothiazide in pharmaceutical preparations using derivative spectrophotometry and chromatographic-densitometric method.

    Science.gov (United States)

    Stolarczyk, Mariusz; Maślanka, Anna; Apola, Anna; Krzek, Jan

    2013-01-01

    Two methods, spectrophotometric and chromatographic-densitometric ones, were developed for determination of losartan potassium, quinapril hydrochloride and hydrochlorothiazide in pharmaceutical preparations. Spectrophotometric method involved derivative spectrophotometry and zero order spectrophotometry. The measurements were carried out at lambda = 224.0 nm for quinapril, lambda = 261.0 nm for hydrochlorothiazide and lambda = 270.0 nm for losartan when the derivative spectrophotometry was applied and lambda = 317.0 nm when zero order spectrophotometry was applied for the determination of hydrochlorothiazide. In chromatographic-densitometric studies high performance thin layer chromatography (HPTLC) plates were used as stationary phase and a mixture of solvents n-butanol : acetic acid : water (15 : 5 : 1, v/v/v) as mobile phase. Under the established conditions good resolution of examined constituents was obtained. Retardation factor for quinapril hydrochloride was R(f) - 0.70, for losartan potassium R(f) - 0.85 and for hydrochlorothiazide R(f) - 0.78. The developed methods are characterized by high sensitivity and accuracy. For quantitative analysis, densitometric measurements were carried out at lambda = 218.0 nm for quinapril, lambda = 275.0 nm for hydrochlorothiazide and = 232.0 nm for losartan.

  13. Analgesic Effects of Meloxicam, Morphine Sulfate, Flunixin Meglumine, and Xylazine Hydrochloride in African-Clawed Frogs (Xenopus laevis)

    Science.gov (United States)

    Coble, Dondrae J; Taylor, Douglas K; Mook, Deborah M

    2011-01-01

    We evaluated analgesic use and analgesiometry in aquatic African-clawed frogs (Xenopus laevis). We used the acetic acid test (AAT) to assess the analgesic potential of systemic xylazine hydrochloride, meloxicam, flunixin meglumine, and morphine sulfate after injection into the dorsal lymph sac. Flunixin meglumine provided better analgesia than did the other drugs, most evident at 5 and 9 h after administration. Because the AAT was associated with the development of dermal lesions, we discontinued use of this assay and chose the Hargreaves test as an alternative method of measuring nociception in Xenopus. This assay is commonly performed in rodents, but its efficacy in an aquatic species such as Xenopus was unknown prior to this study. We found that the Hargreaves test was an effective measure of nociception in Xenopus, and we used it to evaluate the effectiveness of the nonopiod agents xylazine hydrochloride, meloxicam, and flunixin meglumine both in the absence of surgery and after surgical oocyte harvest. Similar to findings from the AAT, flunixin meglumine provided better analgesia in the Hargreaves test than did the other agents when analyzed in the absence of surgical intervention. Results were equivocal after oocyte harvest. Although surgical oocyte harvest is a common procedure in Xenopus, and currently there are no published recommendations for analgesia after this invasive surgery. Future studies are needed to clarify the efficacy of nonsteroidal antiinflammatory drugs for that purpose. PMID:21640031

  14. Visible Spectrophotometric determination of Chlorpheniramine maleate and Diphenhydramine hydrochloride in raw and dosage form using Potassium permanganate

    Directory of Open Access Journals (Sweden)

    Mohammed Al Bratty

    2016-05-01

    Full Text Available Two simple, rapid and sensitive spectrophotometric methods developed for Chlorpheniramine Maleate (CPM and Diphenhydramine Hydrochloride (DPH determination in pure and pharmaceutical preparation using Potassium Permanganate. The solvent system used was potassium permanganate. The method developed by adding a known amount of permanganate to CPM and DPH in acid and alkaline medium, the unreacted permanganate was determined at 550 nm; method A and bluish green colour of Manganate at 610 nm; method B. In method A decrease in absorbance or method B increase in absorbance as concentrations of CPM and DPH was measured. Beer’s law was obeyed at a range of 2.5 to 20 μg / ml in both the methods A and B. The method was validated as per International Council for Harmonisation guideline. The proposed methods were effectively used for the determination of CPM and DPH in commercially available syrup. The average percentages of recoveries of CPM were 99.20 ± 1.29% (method A, 100.6% ± 1.43% (method B; DPH 98.50 ± 1.29% (method A and 100.20 ± 1.43% (method B. The methods were efficiently validated and used for quantitative determination of Chlorpheniramine maleate and Diphenhydramine Hydrochloride in pure and syrup preparations.

  15. Effects of betaine hydrochloride on ruminal fermentation in vitro%甜菜碱盐酸盐对人工瘤胃发酵参数的影响

    Institute of Scientific and Technical Information of China (English)

    张善芝; 韩兆玉

    2012-01-01

    采用人工瘤胃体外发酵方法对培养液中甜菜碱盐酸盐不同质量浓度(0、16.7和33.4 mg· L-1)下,各时间段(3、6、12、18和24h)的体外产气量、pH值、干物质降解率、氨态氮(NH3-N)、挥发性脂肪酸(VFA)、乳酸和菌体蛋白含量的测定,探讨甜菜碱盐酸盐对人工瘤胃发酵功能的影响.结果显示:培养液中甜菜碱盐酸盐的质量浓度为33.4 mg· L-1时,瘤胃液中乙酸、丙酸、丁酸、总VFA的浓度显著升高(P<0.01),干物质降解率显著提高(P<0.01),乳酸浓度显著降低(P<0.05);而甜菜碱盐酸盐对瘤胃液pH值、产气量、菌体蛋白含量、NH3-N浓度无显著影响.结论:甜菜碱盐酸盐可改善人工瘤胃发酵性能.%Mixed ruminal liquid and artifial saliva were cultured in anaerobious environment for 24 h in vitro. The betaine hydrochloride was added to the media at different concentrations(0,16. 7 and 33. 4 mg·L-1 ) ,and the gas production in vitro,pH value, the degradation of dry matter, NH3 -N, volatile fatty acids ( VFA ) , lactic acid and bacteria protein productions were detected. The results showed that,when the concentration was 33.4 mg·L-1 ,betaine hydrochloride could increase the concentration of acetic acid,propionate acid,butyric acid and total volatile fatty acids(tVFA) (P0. 05) adding betaine hydrochloride on pH value, gas yield, bacteria protein and NH3 -N concentrations in rumen. Conclusion: the betaine hydrochloride promoted the ruminal fermentation in vitro.

  16. [Examination of effectiveness of olopatadine hydrochloride in atopic dermatitis].

    Science.gov (United States)

    Shimizu, Tadamichi; Mashiko, Maki; Shimizu, Hiroshi

    2005-02-01

    Subjective/objective symptoms (itching, papula, erythema, lichenification, desquamation, scratching, erosion) and the levels of IgE, LDH, interleukin (IL) -6, thymus and activation-regulated chemokine (TARC) were compared before and after administering olopatadine hydrochloride (ALLELOCK tablets) to 17 atopic dermatitis (AD) patients. Subject/objective symptoms improved significantly after administering the agent, and the total dosage of the combined topical steroids was also significantly decreased after administration (p<0.05), although IgE, IL-6 and LDH levels did not change, TARC was significantly decreased (p<0.05). The correlation between the levels of IgE, IL-6, LDH and TARC before and after the administration was examined. There was a positive correlation between IgE and TARC (r=0.62, p<0.01) and between IL-6 and TARC (r=0.78, p<0.01). Olopatadine hydrochloride is therefore useful in improving the symptoms in AD, and TARC may be used as an indicator of the symptom improvement.

  17. Growth of glycine ethyl ester hydrochloride and its characterizations

    Science.gov (United States)

    Venkatesan, G.; Pari, S.

    2016-11-01

    Single crystal of glycine ethyl ester hydrochloride by slow evaporation method is reported. The grown crystal characterized by single crystal X-ray diffraction, FT-IR, UV-Vis-NIR and fluorescence spectroscopy. It is established that the crystal falls under the monoclinic system and space group P21/c with the cell parameters as: a=8.565 Å, b=12.943 Å, c=6.272 Å, α=γ=90°, β=103.630º. UV-Vis-NIR spectrum shows indirect allowed transition with a band gap of 5.21 eV and other optical properties are measured. The crystal is also shown to have a high transmittance in the visible region. The third order nonlinear property and optical limiting have been investigated using Z-Scan technique. Complex impedance spectrum measured at the dc conductivity. Dependence of dielectric constant, dielectric loss and ac conductivity on frequency at different temperature of applied ac field is analyzed. The mechanical behavior has been assessed by Vickers microhardness indenter. The thermal behavior of glycine ethyl ester hydrochloride was analyzed using TG/DTA thermal curves. From the thermal study, the material was found to possess thermal stability up to 174 °C. The predicted NLO properties, UV-Vis transmittance and Z-scan studies indicate that is an attractive material for photonics optical limiting applications.

  18. SPECTROPHOTOMETRIC, ATOMIC ABSORPTION AND CONDUCTOMETRIC ANALYSIS OF TRAMADOL HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Sara M. Anis

    2011-09-01

    Full Text Available Six simple and sensitive spectroscopic and conductometric procedures (A-F were developed for the determination of tramadol hydrochloride. Methods A, B and C are based on the reaction of cobalt (II thiocyanate with tramadol to form a stable ternary complex, which could be measured by spectrophotometric (method A, atomic absorption (method B or conductometric (method C procedures. Methods D and E depend on the reaction of molybdenum thiocyanate with tramadol to form a stable ternary complex, measured by spectrophotometric means (method D or by atomic absorption procedures (method E, while method F depends on the formation of an ion pair complex between the studied drug and bromothymol blue which is extractable into methylene chloride. Tramadol hydrochloride could be assayed in the range of 80-560 and 40-–220 μg ml-1, 1-15 mg ml-1 and 2.5-22.5, 1.25-11.25 and 5-22 μg ml-1 using methods A,B,C,D,E and F, respectively. Various experimental conditions were studied. The results obtained showed good recoveries. The proposed procedures were applied successfully to the analysis of tramadol in its pharmaceutical preparations and the results were favorably comparable with the official method.

  19. FORMULATION AND DISSOLUTION STUDY OF DILTIAZEM HYDROCHLORIDE IMMEDIATE RELEASE TABLETS

    Directory of Open Access Journals (Sweden)

    BRAHMAIAH BONTHAGARALA

    2014-08-01

    Full Text Available Objective: The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV’S in different ratios. Methods: In the present study, design of oral immediate release tablets of Diltiazem hydrochloride by direct compression technique was carried out. Results: The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate . To determine the best fit dissolution profile for the dosage forms. Diltiazem hydrochloride tablets were formulated by using microcrystalline cellulose (diluent, potato starch, acacia (binder and magnesium stearate (lubricant. The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. Conclusion: The Invitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

  20. Modulation of venlafaxine hydrochloride release from press coated matrix tablet

    Directory of Open Access Journals (Sweden)

    Gohel M

    2008-01-01

    Full Text Available The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3 2 full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion. The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

  1. TRIMETAZIDINE HYDROCHLORIDE TRANSDERMAL PATCH: FORMULATION AND IN-VITRO EVALUATION

    Directory of Open Access Journals (Sweden)

    Sarfaraz Md

    2012-07-01

    Full Text Available The present study was carried out to formulate and evaluate matrix-type transdermal formulations containing trimetazidine hydrochloride with polymers such as carboxymethyl chitosan and hydroxypropylmethylcellulose (HPMC 5cps by solvent evaporation technique with glycerin, as plasticizer. The prepared patches were tested for their physicochemical characteristics such as thickness, weight variation, drug content uniformity, folding endurance and tensile strength. The partition coefficient study was performed using n-octanol as the organic phase and phosphate buffer pH 7.4 as an aqueous phase and it was found to be 1.01. In-vitro release studies of trimetazidine hydrochloride-loaded patches in phosphate buffer (pH, 7.4 exhibited drug release in the range of 89.40 to 92.10 % in 24 hrs. The parameter flux (J was calculated and it was in the range of 1.325 to 2.898 mg/cm2/hr. Based on optimization studies, patches containing carboxymethyl chitosan patches were chosen as optimized formulation. Skin irritation studies were performed on optimized transdermal patch and were found to be free of irritation. The patches were subjected to short term stability studies and were found stable. FTIR studies revealed no interactions between drug and excipients. Data of in vitro release from optimized patches were fit in to different equations and kinetic models such as zero order, first-order, Higuchi and Korsmeyer-Peppas models to explain release kinetics.

  2. 维拉佐酮盐酸盐%vilazodone hydrochloride

    Institute of Scientific and Technical Information of China (English)

    李赛

    2011-01-01

    由Trovis Pharma LLC制药公司研制的维拉佐酮盐酸盐(vilazodone hydrochloride)于2011年1月21日由FDA批准上市,商品名为Viibryd,用于治疗成年人重度抑郁症(major depressive disorder,MDD)[1].Viibryd将以10 mg、20 mg和40 mg片剂上市.Viibryd中文化学名称:5-[4-[4-(5-氰基-1H-吲哚-3-基)丁基]-1-哌嗪基]-2-苯并呋喃草酰胺盐酸盐;英文化学名称:5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperaz-inyl]-2-benzofurancarboxamide hydrochloride;分子式:C26-H27N5O2 ·HCl;分子量:477.99;CAS登记号:163521-08-2.

  3. Structural characterisation and dehydration behaviour of siramesine hydrochloride.

    Science.gov (United States)

    Zimmermann, Anne; Tian, Fang; de Diego, Heidi Lopez; Frydenvang, Karla; Rantanen, Jukka; Elema, Michiel Ringkjøbing; Hovgaard, Lars

    2009-10-01

    In this study the crystal structures of siramesine hydrochloride anhydrate alpha-form and siramesine hydrochloride monohydrate were determined, and this structural information was used to explain the physicochemical properties of the two solid forms. In the crystal structure of the monohydrate, each water molecule is hydrogen bonded to two chloride ions, and thus the water is relatively strongly bound in the crystal. No apparent channels for dehydration were observed in the monohydrate structure, which could allow transmission of structural information during dehydration. Instead destructive dehydration occurred, where the elimination of water from the monohydrate resulted in the formation of an oily phase, which subsequently recrystallised into one or more crystalline forms. Solubility and intrinsic dissolution rate of the anhydrate alpha-form and the monohydrate in aqueous media were investigated and both were found to be lower for the monohydrate compared to the anhydrate alpha-form. Finally, the interactions between water molecules and chloride ions in the monohydrate as well as changes in packing induced by water incorporation could be detected by spectroscopic techniques.

  4. OPTIMIZATION OF CONCENTRATION OF POLYHEXANIDE HYDROCHLORIDE IN MULTIPURPOSE SOLUTION.

    Directory of Open Access Journals (Sweden)

    A. Arora

    2010-01-01

    Full Text Available There are a number of foreign pathogenic microorganisms like viruses, bacteria, yeast, fungi and protozoa which can inadvertently be introduced into eye via contact lens and hence disinfection is a vital part. Multifunctional solutions are generally intended to combine the action of cleaning disinfecting, rinsing lubricating deproteinising and soaking in one single product.In order to optimization of concentration of Polyhexanide hydrochloride in multipurpose solution some microbiological studies were performed by taking five microorganisms which are more prevalent in the infected eye condition. The nutrient agar and sabourad's agar media were used for bacteria and yeast mould respectively. The media were prepared as per I.P and sterilised by autoclaving and poured into Petri plates. The media when cooled to 42°C, 0.5 ml of the culture was added.The optimum concentration of Polyhexanide hydrochloride is 0.0002% which is an effective concentration against five microorganisms that are most prevalent in the infected eye condition.It was concluded that the multipurpose solution containing 2.0 g/ml of polyhexanide were found to be better in terms of antimicrobial activity

  5. Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

    Science.gov (United States)

    Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

    2008-01-01

    The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

  6. Formulation and evaluation of transdermal patches of papaverine hydrochloride

    Directory of Open Access Journals (Sweden)

    Shah Samip

    2010-01-01

    Full Text Available Transdermal patches of papaverine hydrochloride were prepared by the solvent casting method using ethyl cellulose: PVP, PVA: PVP and Eudragit RL-100: Eudragit RS-100 using different ratios. The physicochemical parameters such as flexibility, thickness, smoothness, weight variation, moisture content, hardness and tensile strength were evaluated for the prepared patches. The formulation exhibited flexibility, uniform thickness and weight, smoothness, good drug content (92 to 96%, and little moisture content. The in vitro diffusion studies were carried out using modified Keshery-Chein cell using cellophane as the diffusion membrane and the formulation followed the Higuchi diffusion mechanism. The formulation containing PVA: PVP as polymers showed faster release rate (hydrophilic polymers compared to Eudragit RL-100: Eudragit RS-100 (hydrophobic polymers or combination of hydrophilic and hydrophobic polymers (ethyl cellulose and PVP. The stability studies indicated that all the patches maintained good physicochemical properties and drug content after storing the patches in different storage conditions. Compatibility studies indicated that there was no interaction between the drug and polymers. In vivo studies showed that papaverine hydrochloride helps in decreasing the effect of isoproterenol-induced myocardial necrosis. Hence, the aim of the present study was to prepare the sustained release formulation (Transdermal patches of the drug using different blend of polymers. The formulated patches containing the hydroplilic polymers showed best release rate of drug.

  7. Formulation and evaluation of tramadol hydrochloride rectal suppositories

    Directory of Open Access Journals (Sweden)

    Saleem M

    2008-01-01

    Full Text Available Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000 with high molecular weight (4000 and 6000 in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.

  8. A novel and rapid microbiological assay for ciprofloxacin hydrochloride

    Institute of Scientific and Technical Information of China (English)

    Edith Cristina Laignier Cazedey; Hérida Regina Nunes Salgado

    2013-01-01

    The present work reports a simple, fast and sensitive microbiological assay applying the turbidimetric method for the determination of ciprofloxacin hydrochloride (CIPRO HCl) in ophthalmic solutions. The validation method yielded good results and included excellent linearity, precision, accuracy and specificity. The bioassay is based on the inhibitory effect of CIPRO HCl upon the strain of Staphylococcus epidermidis ATCC 12228 used as the test microorganism. The results were treated statistically by analysis of variance (ANOVA) and were found to be linear (r¼0.9994, in the range of 14.0-56.0 mg/mL), precise (intraday RSD%¼2.06;interday RSD%¼2.30) and accurate (recovery ¼ 99.7%). The turbidimetric assay was compared to the UV spectrophotometric and HPLC methods for the same drug. The turbidimetric bioassay described on this paper for determination of ciprofloxacin hydrochloride in ophthalmic solution is an alternative to the physicochemical methods disclosed in the literature and can be used in quality control routine.

  9. Growth of glycine ethyl ester hydrochloride and its characterizations

    Energy Technology Data Exchange (ETDEWEB)

    Venkatesan, G.; Pari, S., E-mail: sparimyur@gmail.com

    2016-11-15

    Single crystal of glycine ethyl ester hydrochloride by slow evaporation method is reported. The grown crystal characterized by single crystal X-ray diffraction, FT-IR, UV–Vis–NIR and fluorescence spectroscopy. It is established that the crystal falls under the monoclinic system and space group P21/c with the cell parameters as: a=8.565 Å, b=12.943 Å, c=6.272 Å, α=γ=90°, β=103.630º. UV–Vis–NIR spectrum shows indirect allowed transition with a band gap of 5.21 eV and other optical properties are measured. The crystal is also shown to have a high transmittance in the visible region. The third order nonlinear property and optical limiting have been investigated using Z-Scan technique. Complex impedance spectrum measured at the dc conductivity. Dependence of dielectric constant, dielectric loss and ac conductivity on frequency at different temperature of applied ac field is analyzed. The mechanical behavior has been assessed by Vickers microhardness indenter. The thermal behavior of glycine ethyl ester hydrochloride was analyzed using TG/DTA thermal curves. From the thermal study, the material was found to possess thermal stability up to 174 °C. The predicted NLO properties, UV–Vis transmittance and Z-scan studies indicate that is an attractive material for photonics optical limiting applications.

  10. Intestinal Anisakiasis Treated Successfully with Prednisolone and Olopatadine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Hideki Toyoda

    2016-02-01

    Full Text Available The clinical characteristic of gastrointestinal anisakiasis is severe abdominal pain after eating raw fish. Intestinal anisakiasis is more uncommon than gastric anisakiasis. Most patients with intestinal anisakiasis need hospitalization because anisakiasis can cause intestinal obstruction, ileus, peritonitis or intestinal perforation. We report a case of intestinal anisakiasis. A 43-year-old woman presented with symptoms of intermittent abdominal pain 2 days after eating raw fish. Her brother had eaten the same food and had been suffering from gastric anisakiasis. Abdominal ultrasonography in this patient showed localized jejunal wall thickening with dilated lumen of proximal jejunum and ascites. According to the clinical course and examinations, she was diagnosed with intestinal anisakiasis. Administration of prednisolone 5 mg/day and olopatadine hydrochloride 10 mg/day improved her symptoms quickly without hospitalization. Prednisolone was administered for 10 days, and olopatadine hydrochloride was administered for a total of 6 weeks according to ultrasonographic findings. Six months after the treatment, the abdominal ultrasonography demonstrated normal findings. This case demonstrates that ultrasonography was quite useful for the diagnosis and surveillance of intestinal anisakiasis. Furthermore, treatment with corticosteroid and an antiallergic agent could be an option for patients with intestinal anisakiasis.

  11. Structural characterization of anhydrous naloxone- and naltrexone hydrochloride by high resolution laboratory X-ray powder diffraction and thermal analysis.

    Science.gov (United States)

    Sugimoto, Kunihisa; Dinnebier, Robert E; Zakrzewski, Marek

    2007-12-01

    The crystal structures of the analgesic compounds anhydrous naloxone and naltrexone hydrochloride were determined ab initio from high resolution laboratory X-ray powder diffraction data. Both compounds crystallize in the orthorhombic space group P2(1)2(1)2(1) with lattice parameters of a = 14.6588(10) A, b = 17.4363(9) A, c = 7.96200(22) A, and V = 2035.06(23) A(3) for naloxone hydrochloride and a = 15.4560(5) A, b = 14.9809(4) A, c = 7.84121(18) A, and V = 1815.58(11) A(3) for naltrexone hydrochloride. The crystal structure of anhydrous naloxone hydrochloride forms one-dimensional chains through hydrogen bonds. In the crystal structure of anhydrous naltrexone hydrochloride, two-dimensional sheets are formed by hydrogen bonds. The dehydration processes of naloxone hydrochloride dehydrate and naltrexone hydrochloride tetrahydrate was analyzed by DTA, DSC, TG, and MG.

  12. Efficacy of benzydamine hydrochloride dripping at endotracheal tube cuff for prevention of postoperative sore throat.

    Science.gov (United States)

    Nimmaanrat, Sasikaan; Chokkijchai, Kedsirin; Chanchayanon, Thavat

    2013-10-01

    Postoperative sore throat (POST) is a frequent consequence following ETT intubation, which may negatively affect the postoperative course and patient satisfaction. Benzydamine hydrochloride is a topically-applied non-steroidal anti-inflammatory drug (NSAID). The authors evaluated the analgesic effect of benzydamine hydrochloride dripping on the ETT cuff on POST. Eighty-six patients participated in this randomized controlled trial. They were assigned into either the benzydamine hydrochloride or the control group. The whole ETT cuff was dripped either with 3 ml (4.5 mg) of benzydamine hydrochloride or nothing five minutes prior to anesthesia induction. The incidence and severity of POST at 0, 2, 4, 6, 12 and 24 hours postoperatively were assessed. The potential adverse effects of benzydamine hydrochloride (throat numbness throat burning sensation, dry mouth, and thirst) were also evaluated. Twenty-five patients (58.14%) in each group had POST (p-value = 1). The severity of POST (calculated from affected patients) in both groups at different time points was not significantly different. Patients in the benzydamine hydrochloride group did not have a higher incidence of adverse effects. We found that dripping benzydamine hydrochloride on the ETT cuff neither reduced the incidence of POST nor increased the incidence of adverse effects in comparison with no intervention.

  13. Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

    Science.gov (United States)

    Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

    2014-05-01

    Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

  14. Comparative effects of zilpaterol hydrochloride and ractopamine hydrochloride on live performance and carcass characteristics of calf-fed Holstein steers.

    Science.gov (United States)

    Brown, T R; Sexten, A K; Lawrence, T E; Miller, M F; Thomas, C L; Yates, D A; Hutcheson, J P; Hodgen, J M; Brooks, J C

    2014-09-01

    Holstein steers (n = 2,275) were assigned to 1 of 3 treatments: 1) a control diet containing no β-agonists, 2) a diet that contained zilpaterol hydrochloride (ZH; 8.3 mg/kg [100% DM basis]) for 20 d with a 3-d withdrawal period before harvest, and 3) a diet that contained ractopamine hydrochloride (RH; 30.1 mg/kg [100% DM basis]) for 28 d before harvest. No differences (P ≥ 0.18) were detected between treatments for initial BW, BW at d 28, or DMI. Final BW, BW gain for the last 28 d, total BW gain, ADG for the last 28 d, and overall ADG were greater (P Feeding either β-agonist to calf-fed Holstein steers increased live performance through increased BW, BW gain, and ADG. Furthermore, supplementing calf-fed Holstein steers with ZH provides greater improvements in HCW, LM area, and yield grade components, with a slight decrease in quality grade when compared to calf-fed Holstein steers supplemented with RH.

  15. Antitumor efficacy of poly(dimer acid-dodecanedioic acid) copolymer in mice bearing Sarcoma-180 tumor.

    Science.gov (United States)

    Guo, Wen-Xun; Shi, Zongli; Zeng, Fan-Bing; Liang, Kui; Chen, Xian-Hong; Ai, Yong-Ping; Fang, Min; Sun, Xiao; Zhang, Zhi; Hu, Li-Xin

    2007-08-01

    The drug release profiles of poly(dimer acid-dodecanedioic acid) P(DA-DDDA) copolymer containing 5% adriamycin hydrochloride (ADM) in vitro were evaluated. The biocompatibility of P(DA-DDDA) under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DA-DDDA) copolymers containing 5% adriamycin hydrochloride (ADM) implanted subcutaneously in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (31 +/- 1.5 days) compared to plain subcutaneous injection of ADM (7 +/- 0.9 days). The studies suggest that P(DA-DDDA) copolymer as an effective carrier for antineoplastic drug like adriamycin hydrochloride has a very good prospect in the treatment of noumenon tumors.

  16. The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Peiqi Li

    2015-10-01

    Full Text Available Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN-γ and zoledronate (Zol are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS. At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption.

  17. Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

    Science.gov (United States)

    Zhou, Hui-Yun; Cao, Pei-Pei; Zhao, Jie; Wang, Zhi-Ying; Li, Jun-Bo; Zhang, Fa-Liang

    2014-12-01

    Novel ethyl cellulose/chitosan microspheres (ECCMs) were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 μm. The drug loading efficiency of berberine hydrochloride (BH) loaded in microspheres were affected by chitosan (CS) concentration, EC concentration and the volume ratio of V(CS)/ V(EC). ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid (dHCl) and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCl and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

  18. A degradation study of cefepime hydrochloride in solutions under various stress conditions by TLC-densitometry.

    Science.gov (United States)

    Dąbrowska, Monika; Starek, Małgorzata; Krzek, Jan; Papp, Elżbieta; Król, Piotr

    2015-03-01

    A rapid, accurate and sensitive thin-layer chromatography (TLC) method with densitometric detection has been developed and validated for the determination of cefepime in pharmaceuticals. Chromatographic separation was achieved on a silica gel TLC F254 plates with a mobile phase consisting of ethanol-2-propanol-glacial acetic acid 99.5%-water (4:4:1:3, v/v). Densitometric detection was carried out at wavelength of 266 nm in reflectance/absorbance mode. The validation of the method was found to be satisfactory with high accuracy (from 99.24 to 101.37%) and precision (RSD from 0.06 to 0.36%). Additionally, the stability of cefepime in solution was investigated, including the effect of pH, temperature and incubation time. Favorable retention parameters (Rf , Rs, α) were obtained under the developed conditions, which guaranteed good separation of the studied components. The degradation process of cefepime hydrochloride was described by kinetic and thermodynamic parameters (k, t0.1 , t0.5 and Ea ). Moreover, the chemical properties of degradation products were characterized by the Rf values, absorption spectra, HPLC-MS/MS and TLC-densitometry analysis. As the method could effectively separate the active substance from its main degradation product (1-methylpyrrolidine), it can be employed as a method to indicate the stability of this drug. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Simultaneous determination of amlodipine besylate and benazepril hydrochloride in pharmaceutical dosage form by LC.

    Science.gov (United States)

    Kasawar, Gajanan B; Farooqui, Mazahar N

    2009-12-01

    A rapid, precise, specific, and accurate ultra performance liquid chromatography (UPLC) method has been developed and subsequently validated for simultaneous determination of amlodipine present as amlodipine basylate (AB) and benazepril hydrochloride (BH) in capsule dosage form. The chromatographic separation was achieved on an Acquity UPLC, BEH C8 (100 mm x 2.1 mm, 1.7 microm) column using a photodiode array detector. The mobile phase used consisted of a mixture of phosphate buffer pH 3.0 (0.01 M aqueous potassium dihydrogen phosphate, pH 3.0 adjusted with orthophosphoric acid) and solvent mixture (equal mixture of acetonitrile and methanol) in the ratio of 45:55 (v/v) at a flow rate of 0.3 mL/min. The described method was linear over ranges of 5.21-15.63 microg/mL for AB and 20.24-60.72 microg/mL for BH. The mean recoveries were 100.47 and 99.97% for AB and BH, respectively. The lower limit of quantification was determined on the basis of signal-to-noise ratio method; it is 0.01 microg/mL for AB and 0.019 microg/mL for BH.

  20. Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration.

    Science.gov (United States)

    Ranjbar-Mohammadi, Marziyeh; Zamani, M; Prabhakaran, M P; Bahrami, S Hajir; Ramakrishna, S

    2016-01-01

    Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core-shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core-shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases.

  1. Application of potassium permanganate to spectrophotometric assay of metoclopramide hydrochloride in pharmaceuticals

    Science.gov (United States)

    Devi, O. Zenita; Basavaiah, K.; Vinay, K. B.

    2012-01-01

    Two simple, sensitive, and cost-effective spectrophotometric methods are described for the determination of metoclopramide hydrochloride (MCP) in pharmaceutical dosage forms. The methods are based on a redox reaction between MCP and KMnO4 in alkaline and acid media. Direct spectrophotometry (method A) involves treating MCP with permanganate in an NaOH medium and measuring a bluish green product at 610 nm. In indirect spectrophotometry (method B), MCP is treated with a fixed concentration of KMnO4 in an H2SO4 medium, and after a specified time, the unreacted KMnO4 is measured at 545 nm. Under optimum assay conditions, Beer's law is obeyed over the ranges of 0.75-12.0 and 2.5-30.0 g/ml for methods A and B, respectively. Molar absorptivity values are calculated to be 2.33•104 and 2.66•104 l/mol cm for methods A and B, respectively, and corresponding Sandell's sensitivity values are 0.015 and 0.013 g/cm2. Limits of detection (LOD) and quantification (LOQ) are also reported. The applicability of the developed methods was demonstrated by the determination of MCP in tablet and injection forms. The accuracy and reliability of the proposed methods were further ascertained by recovery studies via standard addition technique.

  2. Simultaneous determination of phenylephrine hydrochloride, guaifenesin, and chlorpheniramine maleate in cough syrup by gradient liquid chromatography.

    Science.gov (United States)

    Amer, Sawsan M; Abbas, Samah S; Shehata, Mostafa A; Ali, Nahed M

    2008-01-01

    A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.

  3. Stability-Indicating LC Method for the Determination of Prasugrel Hydrochloride in Pharmaceutical Dosage Form.

    Science.gov (United States)

    Ahirrao, Vinod K; Patil, Chabutai S; Bembalkar, Saroj B; Ubale, Sanjay B; Marathe, Rajendra P; Nawale, Rajesh B; Landge, Mahadev G; Pawar, Rajendra P

    2012-01-01

    A simple, rapid and precise method was developed for the quantitative estimation of prasugrel hydrochloride in pharmaceutical dosage form. A chromatographic separation of prasugrel and its degradants was achieved with Zorbax XDB C(8), 150 × 4.6 mm, 3.5μm analytical column using aqueous solution of 0.05 M ammonium acetate pH 4.5 with acetic acid-acetonitrile (40:60 v/v). The instrumental settings include flow rate of 1.0 ml/min, column temperature at 30°C and detector wavelength of 254 nm using a photodiode array detector. Theoretical plates for prasugrel were 7023. Tailing factor for prasugrel was 1.11. Prasugrel was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Peak homogeneity data of prasugrel was obtained using photodiode array detector in the stressed sample chromatograms, which demonstrated the specificity of the method for the estimation in presence of degradants. The described method showed excellent linearity over a range of 10-300 μg/ml for prasugrel. The correlation coefficient is 0.999. The relative standard deviation of peak area for six measurements is always less than 2%. Overall, the proposed method was found to be suitable and accurate for quantitative determination and stability study of prasugrel in pharmaceutical dosage form.

  4. Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Raghvendra Misra

    2016-01-01

    Full Text Available The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3 and citric acid were used as gas (CO2 generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72±2.49 seconds and duration of floating 24.50±0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr.

  5. Improving the filterability and solid density of ranitidine hydrochloride Form 1.

    Science.gov (United States)

    Mirmehrabi, Mahmoud; Rohani, Sohrab; Murthy, K S Keshava; Radatus, Bruno

    2004-07-01

    Ranitidine hydrochloride Form 1 produced by the original method (Price et al., 1978 US patent) has poor filtration and drying characteristics, which make it less desirable commercially in comparison with Form 2. This article shows that the operating parameters have significant influence on the final properties of Form 1. In terms of filterability and solid bulk density, it was found that at a higher temperature (approximately 48 degrees C), the viscosity of the slurry decreased and improved product quality as compared with operating at room temperature (approximately 25 degrees C). It was found that the rapid addition of acid to the ranitidine base increased product density but led to higher residual solvent inclusion. The presence of excess ranitidine base in the solution and also the manner of reactant addition had a significant influence on the onset of nucleation and the rate of crystallization. The best results in terms of filterability and bulk solid density were obtained using an initial pH of 5.3 and then increasing it to 6.3-6.4 after the onset of nucleation.

  6. Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride.

    Science.gov (United States)

    Cheng, Xiongkai; Sun, Min; Gao, Yan; Cao, Fengliang; Zhai, Guangxi

    2011-08-01

    The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

  7. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    Science.gov (United States)

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.

  8. Probing conformational stability and dynamics of erythroid and nonerythroid spectrin: effects of urea and guanidine hydrochloride.

    Directory of Open Access Journals (Sweden)

    Malay Patra

    Full Text Available We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl. Fluorescence and circular dichroism (CD spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS. Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20 for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from.

  9. Probing Conformational Stability and Dynamics of Erythroid and Nonerythroid Spectrin: Effects of Urea and Guanidine Hydrochloride

    Science.gov (United States)

    Patra, Malay; Mukhopadhyay, Chaitali; Chakrabarti, Abhijit

    2015-01-01

    We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD) spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

  10. Determination of Cyproheptadine hydrochloride in Pure and Pharmaceutical forms : A Spectrophotometric study

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    Sayanna

    2015-09-01

    Full Text Available Siimple and sensitive extractive spectrophotometric methods have been described for the determination of Cyproheptadine hydrochloride (CPH in pure form and in pharmaceutical formulations. The developed methods involved formation of coloured chloroform extractable ion-pair complexes of the CPH with triphenyl methane dyes viz., bromothymol blue (BTB, bromocresol green (BCG and bromocresol purple (BCP in acidic medium. The extracted complexes showed absorbance maxima at 419, 419 and 405nm with use of the above dyes, respectively. Beer’s law is obeyed in the concentration ranges 3.0-25, 2.5-22.5 and 1.5-25μg/ml with BTB, BCG and BCP respectively. The stoichiometry of the complex is found to be 1:1 in each case. The effect of concentration of dye, pH and interference of excipients have been studied and optimized. The limit of detection and limit of quantification have been determined for three methods. The methods are applied to the determination of CPH in commercial tablets and results of analysis are validated statistically through recovery studies also the methods are validated as per the guidelines of ICH.

  11. Recovery of Pd(II) from hydrochloric solution using polyallylamine hydrochloride-modified Escherichia coli biomass.

    Science.gov (United States)

    Park, Jiyeong; Won, Sung Wook; Mao, Juan; Kwak, In Seob; Yun, Yeoung-Sang

    2010-09-15

    A new type of biosorbent able to bind anionic metals was developed by cross-linking of waste biomass Escherichia coli with polyallylamine hydrochloride (PAH). The PAH-modified biomass was investigated for the removal and recovery of Pd(II), in the chloro-complex form, from aqueous solution. The performance of the PAH-modified biomass was evaluated in terms of the following parameters: the solution pH, contact time and initial metal concentration. In the pH edge experiments, the uptake of Pd(II) increased with increasing pH. Pd(II) biosorption proceeded rapidly in the first 10 min, with almost complete equilibrium being achieved within 60 min. Moreover, the isotherm data showed that the maximum uptakes of Pd(II) were 265.3mg/g at pH 3 and 212.9 mg/g at pH 2, respectively. After incineration of the Pd-loaded PAH-modified biomass, metallic palladium was recovered in the ash. X-ray photoelectron spectroscopy (XPS) results confirmed that the palladium was recovered in two valency states: zero-valent and divalent palladium (as PdO). Therefore, we concluded that PAH-modified biomass is a useful and cost-effective biosorbent for the recovery of anionic precious metals as chloro-complex solutions containing hydrochloric acid produced from metal refining processes.

  12. IMPROVEMENT OF PAPER PROPERTIES OF RECYCLED UNBLEACHED SOFTWOOD KRAFT PULPS BY POLY(ALLYLAMINE HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Paulina Mocchiutti

    2011-02-01

    Full Text Available Polyelectrolytes containing amine functional groups such as PAH (poly(allylamine hydrochloride can be useful, under certain conditions, for improving paper strength. In this work, the charge density of PAH was determined at different pH and ionic strengths; PAH adsorption onto the cellulosic fibers was characterized, and the effects of low PAH dosage on the papermaking properties were evaluated. It was found that the ionization of PAH is complete in acid media, but it is partial and depends on the ionic strength in neutral media. The adsorption isotherms of PAH on a recycled pulp from kraft liner allowed us to determine the amount needed to saturate the adsorption capacity of the fibers. For the three ionic strengths analyzed, the swelling of the fibers decreased when PAH was added in an amount corresponding to saturation (0.23% PAH on dried pulp. Nevertheless, the swelling was recovered when the amount of PAH was the double the saturation level (0.46% PAH on dried pulp. At these levels of addition, the papermaking properties were clearly improved, especially compressive strengths SCT (short compressive test and CMT (concora medium test. The Page equation of tensile strength showed that PAH improved the shear bond strength, while the relative bonding area slightly decreased.

  13. A VALIDATED RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF FLUOXETINE HYDROCHLORIDE AND OLANZAPINE IN PHARMACEUTICAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    M.M.Eswarudu

    2012-04-01

    Full Text Available A simple, sensitive and precise reverse phase high performance liquid chromatographic method has been developed for the simultaneous estimation of Fluoxetine hydrochloride and Olanzapine in pharmaceutical dosage forms. The mobile phase consisted of Acetonitrile: pot.dihydrogen phosphate buffer: Triethylamine (0.2 % (0.1% v/v ortho phosphoric acid, PH 3.1 in the ratio of 40:60:0.2 v/v/v delivered at a flow rate of 1.0 ml / min and wavelength of detection at 233 nm. The retention times of Fluoxetine and Olanzapine were 1.96 min and 5.59 min respectively. The developed method was validated according to ICH guidelines. The proposed method can be used for determination of these drugs in combined dosage forms.

  14. RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF METFORMIN HYDROCHLORIDE, ROSIGLITAZONE AND SITAGLIPTIN – APPLICATION TO COMMERCIALLY AVAILABLE DRUG PRODUCTS

    Directory of Open Access Journals (Sweden)

    Hitesh P Inamdar et al

    2012-09-01

    Full Text Available A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of anti-diabetic drugs Metformin hydrochloride (MT, Rosiglitazone (RT and Sitagliptin (ST. The separation was achieved on ACE 3 150 mm X 4.6mm, 3.5µm column using gradient method. The mobile phase at a flow rate of 1.5 mL min−1 consisted of 10 mM sodium hexane sulphonate monohydrate and 10 mM Potassium dihydrogen phosphate buffer with acetonitrile and methanol in Gradient ratio. The UV detection was carried out at 210 nm. The forced degradation for these drug substances were performed under Acid, Base, Oxidative, Photolytic and Thermal stress conditions. The method was successfully validated in accordance to ICH guidelines. Further, the validated method was applied for commercially available pharmaceutical dosage form.

  15. Physical and Chemical Characterization of Poly(hexamethylene biguanide Hydrochloride

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    Luiz Henrique C. Mattoso

    2011-06-01

    Full Text Available We present the characterization of commercially available Poly(hexamethylene biguanide hydrochloride (PHMB, a polymer with biocidal activity and several interesting properties that make this material suitable as a building block for supramolecular chemistry and “smart” materials. We studied polymer structure in water solution by dynamic light scattering, surface tension and capacitance spectroscopy. It shows typical surfactant behavior due to amphiphilic structure and low molecular weight. Spectroscopic (UV/Vis, FT-NIR and thermal characterization (differential scanning calorimetry, DSC, and thermogravimetric analysis, TGA were performed to give additional insight into the material structure in solution and solid state. These results can be the foundation for more detailed investigations on usefulness of PHMB in new complex materials and devices.

  16. β-Cyclodextrin-promazine hydrochloride interaction: Conductometric and viscometric studies

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    Mohd. Sajid Ali

    2015-01-01

    Full Text Available Herein we have studied the interaction of β-cyclodextrin (β-CD with the amphiphilic drug promazine hydrochloride (PMZ by using conductimetry and viscometry. From the observed results it was concluded that critical micelle concentration (cmc of the pure drug was lower than the apparent critical micelle concentration (cmc∗ of the drug in the presence of β-CD. The cmc∗ increased on increasing the concentration of β-CD due to the encapsulation of the amphiphilic drug to the hydrophobic cavities of the β-CD which delayed the micelle formation. Viscosity of the solution decreased drastically on the addition of β-CD which further increased on increasing the drug solution. Free energies of micellization (ΔGmic were calculated with the help of degrees of micelle ionization and cmc obtained from the specific conductivity−[PMZ] plots. Micellization was found to be less spontaneous in the presence of cyclodextrin.

  17. Permanent-wave dermatitis: contact allergy to cysteamine hydrochloride.

    Science.gov (United States)

    Landers, Maeran C; Law, Sandra; Storrs, Frances J

    2003-09-01

    Cysteamine hydrochloride (CHC) is a newly recognized sensitizer found in permanent-wave solutions. We report the case of a hairdresser who was found to be allergic to CHC. Our allergic patient was patch-tested to various chemicals found in permanent-wave solutions, including CHC (1.0% in petrolatum). Patch-test reactions were positive to CHC, glyceryl thioglycolate, diglyceryl thioglycolate, p-phenylenediamine (PPD), and PPD through a piece of latex glove. Sixty-four controls to CHC (1.0% in petrolatum) had negative results. Household-weight latex gloves were protective against CHC allergy. Persons with CHC-waved hair were not allergic. CHC contained in "neutral" permanent-wave preparations has been used in American beauty salons since 1993. We briefly discuss the introduction and significance of CHC in permanent waves.

  18. Betahistine hydrochloride in Méniére's disease.

    Science.gov (United States)

    Frew, I J; Menon, G N

    1976-08-01

    A double-blind, placebo-controlled, cross-over clinical trial was performed to assess the effect of betahistine hydrochloride (Serc) in Ménière's disease. The diagnosis was based on paroxysmal attacks of rotational vertigo, with tinnitus, and a fluctuating sensori-neural deafness, together with the results of auditory and vestigular tests. Twenty-eight patients were admitted to the trial over 3 years. Twenty-two patients completed the trial. In total, they received betahistine 32 mg daily, for a period of 16 weeks, and placebo also for the same length of time, preceded in every case by a 4-week pre-treatment period. Daily symptom score cards were kept. There was a statistically significant improvement in favour of the drug with regard to vertigo, tinnitus and deafness. Vertigo was the most responsive symptom. No adverse reactions were observed.

  19. [Characteristics and selectivity of photocatalytic-degradation of tetracycline hydrochloride].

    Science.gov (United States)

    Song, Chen-Yi; Yin, Da-Qiang

    2014-02-01

    The photocatalytic-degradation behavior of tetracycline hydrochloride (TTC) was studied. The catalyst used was photosensitive semiconductor titanium dioxide (TiO2). The results showed that the photocatalytic degradation of TTC was well fitted to first order reaction kinetics model, and the adsorption was the control step of the whole photocatalytic-degradation process, indicating that the main degradation path was the photocatalytic reaction of TTC adsorbed on the surface of TiO2. Besides, through photocatalytic-degradation of the mixed solution of TTC and sulfamethoxazole or amoxicillin, the degradation of the two antibiotics showed obvious selectivity when the pH, TiO2 dosage and other conditions were changed.

  20. FORMULATION AND EVALUATION OF SUSTAINED RELEASE PELLETS OF TRAMADOL HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Baskara Haripriya

    2013-02-01

    Full Text Available The aim of the present research is to develop and evaluate a better sustained release multiple unit pellets (MUP formulation of Tramadol hydrochloride. Dissolution and diffusion controlled systems have classically been of primary importance in oral delivery of medication because of their relative ease of production and cost compared with other methods of sustained or controlled delivery. Most of these systems are solids, although a few liquids and suspension have been recently introduced. The present work aimed at developing SR pellets of Tramadol HCl by Wurster process. FTIR studies showed no unacceptable extra peaks which confirm the absence of chemical interaction between the drug and polymer. Angle of repose, tapped density, bulk density values for the formulations were within the range which indicates that pellets prepared by Wurster process were satisfactory for further studies. The percentage drug content of Tramadol was determined by extraction with methanol and analyzed by using UV-visible spectrophotometer at 271nm.

  1. Accumulation of porphyrins in Propionibacterium acnes by 5-aminolevulinic acid and its esters.

    Science.gov (United States)

    Ogata, Arisa; Hasunuma, Yuya; Kikuchi, Emii; Ishii, Takuya; Ishizuka, Masahiro; Tokuoka, Yoshikazu

    2017-09-01

    We have investigated the accumulation of porphyrins in Propionibacterium acnes (P.acnes) by 5-aminolevulinic acid hydrochloride (ALA) and its esters, ALA methyl ester hydrochloride (mALA), ALA octyl ester hydrochloride (oALA), and ALA benzyl ester hydrochloride (bALA). From the fluorescence spectra of porphyrins accumulated in P.acnes, the order of porphyrin accumulation is as follows: ALA≫mALA≈bALA>oALA (≈0). Moreover, the PDT efficacy is reduced in the order of ALA>mALA≈bALA>oALA (≈without additives). These results confirm that ALA is superior to ALA esters in accumulating porphyrins in P.acnes. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Design and Evaluation of Chronomodulated Drug Delivery of Tramadol Hydrochloride.

    Science.gov (United States)

    Alekya, Thota; Narendar, Dudhipala; Mahipal, Donthi; Arjun, Narala; Nagaraj, Banala

    2017-09-26

    Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

    Directory of Open Access Journals (Sweden)

    Yu Jiang

    2015-01-01

    Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

  4. Sinomenine hydrochloride protects against polymicrobial sepsis via autophagy.

    Science.gov (United States)

    Jiang, Yu; Gao, Min; Wang, Wenmei; Lang, Yuejiao; Tong, Zhongyi; Wang, Kangkai; Zhang, Huali; Chen, Guangwen; Liu, Meidong; Yao, Yongming; Xiao, Xianzhong

    2015-01-23

    Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs). The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN) is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl) is widely used to treat rheumatoid arthritis (RA). However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP) in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA) was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3) puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS)-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM). 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

  5. Formulation optimization of propranolol hydrochloride microcapsules employing central composite design

    Directory of Open Access Journals (Sweden)

    Shivakumar H

    2008-01-01

    Full Text Available A central composite design was employed to produce microcapsules of propranolol hydrochloride by o/o emulsion solvent evaporation technique using a mixture of cellulose acetate butyrate as coat material and span-80 as an emulsifier. The effect of formulation variables namely levels of cellulose acetate butyrate (X 1 and percentage of Span-80 (X 2 on encapsulation efficiency (Y 1 , drug release at the end of 1.5 h (Y 2 , 4 h (Y 3 , 8 h (Y 4 , 14 h (Y 5 , and 24 h (Y 6 were evaluated using the F test. Mathematical models containing only the significant terms were generated for each response parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables exerted a significant influence (P < 0.05 on Y 1 whereas the cellulose acetate butyrate level emerged as the lone factor which significantly influenced the other response parameters. Numerical optimization using desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , and Y 6 for the optimized formulation was found to be 92.86±1.56% w/w, 29.58±1.22%, 48.56±2.56%, 60.85±2.35%, 76.23±3.16% and 95.12±2.41%, respectively which were in close agreement with those predicted by the mathematical models. The drug release from microcapsules followed first order kinetics and was characterized by Higuchi diffusion model. The optimized microcapsule formulation developed was found to comply with the USP drug release test-1 for extended release propranolol hydrochloride capsules.

  6. Biowaiver monographs for immediate release solid oral dosage forms: ciprofloxacin hydrochloride.

    Science.gov (United States)

    Olivera, M E; Manzo, R H; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2011-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing ciprofloxacin hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ciprofloxacin hydrochloride's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and BA data indicate that ciprofloxacin hydrochloride is a BCS Class IV drug. Therefore, a biowaiver based approval of ciprofloxacin hydrochloride containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

  7. Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement

    National Research Council Canada - National Science Library

    Wairkar, Sarika; Gaud, Ram

    The aim of the present work was to prepare a co-amorphous mixture (COAM) of Nateglinide and Metformin hydrochloride to enhance the dissolution rate of poorly soluble Nateglinide. Nateglinide (120 mg...

  8. Myocardial perfusion imaging with higenamine hydrochloride stress studies in diagnosis of coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    周维

    2013-01-01

    Objective To evaluate the stress test efficacy and safety of higenamine hydrochloride,MPI studies were performed in patients with coronary artery disease. Methods Sixty-eight patients with suspected coronary artery

  9. Synthesis of 2-Heterocyclomethyl-5-diphenylmethylenecyclopentanone Hydrochlorides and their Inhibitory Effect on Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Yun Hai ZHANG; Lin Xiang ZHAO; Zhen Jun BIAN; Rui WANG; Fu Yuan SUN

    2006-01-01

    Sixteen new 2-heterocyclomethyl-5-diphenylmethylenecyclopentanone hydrochlorides were designed and synthesized. The growth inhibitory effect of these compounds in vitro was conducted using a MTT assay in human breast cancer T47D cells.

  10. The effect of tramadol hydrochloride on early life stages of fish.

    Science.gov (United States)

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

    2016-06-01

    The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride.

  11. Effects of drotaverine hydrochloride on viability of rat cultured cerebellar granulocytes.

    Science.gov (United States)

    Demushkin, V P; Zhavoronkova, E V; Khaspekov, L G

    2012-02-01

    The neurocytotoxic effect of drotaverine hydrochloride was studied in culture of rat cerebellar granulocytes. Incubation of cells with 100 and 250 μM drotaverine reduced neuronal survival to 60 and 4%, respectively.

  12. Thiamine hydrochloride: An efficient catalyst for one-pot synthesis of quinoxaline derivatives at ambient temperature

    Indian Academy of Sciences (India)

    Omprakash B Pawar; Fulchand R Chavan; Venkat S Suryawanshi; Vishnu S Shinde; Narayan D Shinde

    2013-01-01

    Quinoxaline derivatives have been synthesized in high to excellent yields in the presence of thiamine hydrochloride (VB1) as an inexpensive, non-toxic and metal ion free catalyst at ambient temperature.

  13. Development and validation of new analytical methods for simultaneous estimation of Drotaverine hydrochloride in combination with Omeprazole in a pharmaceutical dosage form

    Directory of Open Access Journals (Sweden)

    Smita Sharma

    2017-02-01

    Full Text Available A rapid and precise method (in accordance with ICH guidelines is developed for the quantitative simultaneous determination of Drotaverine hydrochloride and Omeprazole in a combined pharmaceutical dosage form. Three methods are described for the simultaneous determination of Drotaverine hydrochloride and Omeprazole in a binary mixture. The first method was based on UV-Spectrophotometric determination of two drugs, using Vierordt!s simultaneous equation method. It involves absorbance measurement at 226.8 nm (λmax of Drotaverine hydrochloride and 269.4 nm (λmax of Omeprazole in methanol; linearity was obtained in the range of 5–30 μg ml−1 for both the drugs. The second method was based on HPLC separation of the two drugs using potassium dihydrogen phosphate buffer pH 5.0: Acetonitrile: Triethylamine (60:40:0.5, v/v as a mobile phase. Areas were recorded at 260 nm for both the drugs and retention time was found to be 2.71 min. and 3.87 min for Drotaverine hydrochloride and Omeprazole, respectively at 1.0 mL/min flow rate. The selected chromatographic conditions were found to determine Drotaverine hydrochloride and Omeprazole quantitatively in a combined dosage form without any physical separation. The method has been validated for linearity, accuracy and precision. Linearity was found over the range of 5–30 μg mL−1 for both drugs. The third method was based on HPTLC method for simultaneous quantification of these compounds in pharmaceutical dosage forms. Precoated silica gel 60 F254 plate was used as stationary phase. The separation was carried out using Glacial acetic acid:Cyclohexane:Methanol:(80:15:5 v/v/v as mobile phase. The proposed method was found to be fast, accurate, precise, reproducible and rugged and can be used for a simultaneous analysis of these drugs in combined formulations.

  14. RP-HPLC Determination of vitamins B1, B3, B6, folic acid and B12 in multivitamin tablets

    OpenAIRE

    2005-01-01

    Abstract:Asimple and sensitive reversed-phase, ion-pair HPLC method was developed and validated for the simultaneous determination of B-group vitamins, thiamine chloride hydrochloride (B1), nicotinamide (B3), pyridoxine hydrochloride (B6) and folic acid in Pentovit® coated tablets. The cyanocobalamine (B12) was determined separately, because of its low concentration in the investigated multivitamin preparation. RP-HPLC analysis was performed with a LKB 2150 HPLC system, equipped with a UV/VI...

  15. Fluphenazine hydrochloride radical cation assay: A new, rapid and precise method to determine in vitro total antioxidant capacity of fruit extracts

    Institute of Scientific and Technical Information of China (English)

    Muhammad Nadeem Asghar; Qadeer Alam; Sharoon Augusten

    2012-01-01

    A new procedure based on generation and subsequent reduction of orange-colored fluphenazine hydrochloride radical (FPH·+)is presented for the screening of total antioxidant capacity (TAC) of various fruit matrices.The FPH·+ was obtained by mixing fluphenazine hydrochloride with persulfate (final concentration 2 mmol/L and 0.05 mmmol/L,respectively) in 3 mol/L H2SO4 with constant shaking for 5 min.The solution formed showed maximum absorption as 0.8 ± 0.02 at 500 nm in first-order derivative spectrum.The percent inhibition of the solution increased linearly on addition of increasing mounts of standard antioxidants i.e.,ascorbic acid etc.The TACs of sample citrus juices were calculated in terms of ascorbic acid equivalents (AAEs) by comparing their inhibition curves with that of ascorbic