Naveh N, Muchtar S, Benita S
Goldschleger Eye Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel.
J Ocul Pharmacol. 1994 Fall;10(3):509-20. doi: 10.1089/jop.1994.10.509.
Pilocarpine, a widely used antiglaucoma drug, was incorporated into a newly developed submicron emulsion (pilocarpine emulsion) suitable for local ocular administration. Pilocarpine-Emulsion effect on the intraocular pressure (IOP) was studied following a single dose application in normotensive rabbits. Membrane filtration (steam autoclaving) was found not to affect particle size distribution, zeta potential or pH of the pilocarpine emulsion preparation. A single dose application of pilocarpine emulsion 1.7% (equivalent to 2% pilocarpine hydrochloride) induced a prolonged progressive decrease in IOP in normotensive rabbits, which started at eleven hours post instillation and reached its maximal value of 6.0 +/- 0.2 mmHg at 29 hours. The pressure decreasing effect induced by pilocarpine emulsion treatment followed a pattern different from that generated by generic pilocarpine (Pilocarpine Hydrochloride 2% eye drops); In the latter group, IOP reduction (starting at two hours) persisted during the initial five hours post-instillation, while in the former, the hypotensive effect started at a later stage, and was maintained during a twenty nine hour follow-up causing a greater IOP decrease than in the generic group (% delta IOP of 28.5% and 18%, respectively). In the contralateral eyes of Pilocarpine Emulsion treated rabbits, an ocular hypotensive effect was noted late after application (11 hours through 29 hours post-instillation), while this effect was negligible in rabbits-treated with aqueous pilocarpine. Our findings point to the possibility that the novel preparation of pilocarpine incorporated into submicron emulsion might serve as a long-acting form of pilocarpine which might require a single daily application. Further studies are required to elucidate the mechanism and action of this preparation.
毛果芸香碱是一种广泛使用的抗青光眼药物，被制成一种新开发的适用于眼部局部给药的亚微米乳剂（毛果芸香碱乳剂）。在正常血压的兔子单剂量应用后，研究了毛果芸香碱乳剂对眼压（IOP）的影响。发现膜过滤（蒸汽高压灭菌）不影响毛果芸香碱乳剂制剂的粒径分布、ζ电位或pH值。单剂量应用1.7%的毛果芸香碱乳剂（相当于2%的盐酸毛果芸香碱）可使正常血压的兔子眼压持续长时间逐渐降低，滴注后11小时开始，29小时达到最大值6.0±0.2 mmHg。毛果芸香碱乳剂治疗引起的降压效果与普通毛果芸香碱（2%盐酸毛果芸香碱滴眼液）产生的模式不同；在后者组中，眼压降低（从两小时开始）在滴注后的最初五小时内持续，而在前者组中，降压作用在后期开始，并在29小时的随访期间维持，导致眼压降低幅度大于普通组（分别为28.5%和18%的眼压变化百分比）。在接受毛果芸香碱乳剂治疗的兔子的对侧眼中，应用后较晚（滴注后11小时至29小时）出现眼压降低作用，而在用毛果芸香碱水剂治疗的兔子中这种作用可忽略不计。我们的研究结果表明，掺入亚微米乳剂中的新型毛果芸香碱制剂可能作为毛果芸香碱的长效形式，可能只需每日应用一次。需要进一步研究以阐明该制剂的作用机制。
