天然水蛭素水凝胶的皮肤渗透性能及毒理学考察

目的：探讨天然水蛭素凝胶经皮渗透给药的可行性及其对动物皮肤的毒性作用。方法：制备天然水蛭素凝胶，采用改良的Franz扩散池进行经皮渗透试验，使用Markwardt法检测水蛭素活性。选择健康Wistar大鼠进行急性皮肤毒性试验、单次及多次给药皮肤刺激性试验，健康豚鼠进行皮肤致敏性试验。结果：试验组的纤维蛋白原凝结时间均有延迟（P<0.05），于3 h时达最大值（85.4±1.454）s，而对照组纤维蛋白原凝结时间则无明显延迟；短期内大剂量使用天然水蛭素凝胶对皮肤无毒性，对Wistar大鼠完整皮肤和破损皮肤均无刺激性，对豚鼠完整皮肤无致敏性。结论：天然水蛭素可渗透进入完整皮肤组织，其凝胶剂皮肤局部用药对试验动物较为安全。

Research of Skin Penetration Properties and Toxicology of Natural Hirudin Hydrogels

Objective: To discuss feasibility of permeation percutaneous administration of natural hirudin hydrogels and its toxic action on animal skin. Method: Natural hirudin hydrogels was prepared, improved Franz diffusion cells was adopted to make a permeability test, activity of natural hirudin was determined by Markwardt.Health Wistar rats were adopted to take an acute position skin test and single or multiple dose skin irritation test, health guinea pigs were used to make skin sensitization test. Result: Fibrinogen clotting times of experimental groups were delayed with P<0.05, it reached the maximum of (85.4±1.454) s at 3 h, while the control group had no significant delay;High-dose of natural hirudin hydrogels in short-term had no toxicity for skin, and no irritation for intact skin and broken skin of Wistar rats, no sensitization for intact skin of guines pigs. Conclusion: Natural hirudin could penetrate into intact skin tissue, its gels was safety for skin topical administration of experimental animals.