Ayaki, Masahiko; Yaguchi, Shigeo; Iwasawa, Atsuo; Koide, Ryohei
The cytotoxicity of a range of commercial ophthalmic solutions in the presence and absence of preservatives was assessed in human corneal endothelial cells (HCECs), corneal epithelia and conjunctival epithelia using in vitro techniques. Cell survival was measured using the WST-1 assay for endothelial cells and the MTT assay for epithelial cells. Commercially available timolol, carteolol, cromoglicate, diclofenac, bromfenac and hyaluronic acid ophthalmic solutions were assessed for cytotoxicity in the presence and absence of preservatives. The preservatives benzalkonium, chlorobutanol and polysorbate were also tested. The survival of cells exposed to test ophthalmic solutions was expressed as a percentage of cell survival in the control solution (distilled water added to media) after 48 h exposure. HCEC survival was 20-30% in ophthalmic solutions diluted 10-fold. The survival of HCEC was significantly greater in all solutions in the absence of preservative than in the presence of preservative. The survival of corneal and conjunctival epithelia was consistent with that of HCECs for all test ophthalmic solutions. The preservatives polysorbate and benzalkonium were highly cytotoxic with cell survival decreasing to 20% at the concentration estimated in commercial ophthalmic solutions. By comparison, the survival of cells exposed to chlorobutanol was 80% or greater. The cytotoxicity of ophthalmic solutions to HCEC, corneal epithelia and conjunctival epithelia decreased in the absence of preservative.
Nagaoka, S.; Masaki, H.; Aoyama, Y.; Yoshida, A.
Comparison of the effects of excess dietary tyrosine, DDT, chlorobutanol (Chloretone) or butylated hydroxyanisole (BHA) on serum cholesterol, hepatic activities of the rate-limiting enzyme of cholesterol synthesis,3-hydroxy-3-methylglutaryl coenzyme A reductase and in vivo rates of the hepatic cholesterol synthesis measured by 3 H 2 O incorporation were investigated in rats. Serum cholesterol concentration was significantly higher in rats fed the DDT, chlorobutanol, BHA or excess tyrosine diets than in rats fed the control diet for 7 days. Serum cholesterol concentration remained higher compared to control rats when excess tyrosine was fed for 21 d. When rats were fed a basal diet after feeding a tyrosine excess diet for 2 wk, liver weight and serum cholesterol level returned to normal within 7 d. The incorporation of 3 H 2 O into liver cholesterol and the activity of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase were greater in rats fed excess tyrosine or certain xenobiotics than in control rats. Present results suggested that the increase in serum cholesterol concentration due to excess dietary tyrosine or certain xenobiotics is mainly attributable to the stimulation of liver cholesterol synthesis
Gopal, N.G.S.; Rajagopalan, S.; Sharma, G.
The paper deals with some studies carried out to evaluate the feasibility of radiation sterilization or treatment of some medical products and pharmaceuticals of immediate importance to their respective industries. The products include penicillin G sodium, ampicillin sodium, tetracyclin hydrochloride ointment,hydrocortisone acetate and its ointment, aqueous sodium chloride solutions (0.9 and 20%), fluorescein sodium strips, urea, ethylmorphine hydrochloride, aqueous solution of chlorobutanol and one of its commercial preparations, phenylmercuric nitrate and its aqueous solutions, aqueous solutions of methyl and propyl paraben, lactose, gum karaya, absorbent cotton and poly-(vinyl chloride) based medical products. The irradiated products have been examined for pharmacopoeial specifications wherever available. In general the products have been examined for changes in colour, pH, ultra-violet and infra-red absorption spectra. Thin-layer chromatographic analyses have been carried out to establish the purity of some of the irradiated products. The feasibility or otherwise of radiation sterilization or treatment of the various products from the physicochemical and microbiological (pharmacological) clinical considerations is also described. (author)
Li, Xin; Du, Lina; Chen, Xu; Ge, Pingju; Wang, Yu; Fu, Yangmu; Sun, Haiyan; Jiang, Qingwei; Jin, Yiguang
Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its viscosity was up to 7.63 Pas at 37 °C. Furthermore, penetration enhancers and bacterial inhibitors were added and their fractions in the ISG were optimized based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether-β-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as the penetration enhancer and the bacterial inhibitor, respectively. The Fick's diffusion and dissolution of KT could drive it continuous release from the dually sensitive ISG according to the in vitro investigation. Two methods, writhing frequencies induced by acetic acid and latency time of tails retracting from hot water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse models. The writhing frequencies significantly decreased and the latency time of tail retracting was obviously prolonged (pthermo- and ion-sensitive KT ISG had appropriate gelation temperature, sustained drug release, improved intranasal absorption, obvious pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising intranasal analgesic formulation. Copyright © 2015. Published by Elsevier B.V.