溶解型青蒿素贴剂探究.docVIP

溶解型青蒿素贴剂探究 　 作者：王乃婕,邱琳,杜丰,梁秉文,叶祖光 【摘要】 目的 通过对压敏胶、结晶抑制剂、促渗剂的筛选,研究溶解型青蒿素贴剂的处方工艺。方法 采用TK-6A型透皮扩散仪,以SD大鼠腹部皮肤为透皮屏障,以透皮速率为考察指标,筛选压敏胶、结晶抑制剂、促渗剂。结果 青蒿素在国民淀粉压敏胶中透皮速率最高,PVP K30对青蒿素结晶抑制效果较好,各促渗剂对青蒿素促渗作用大小依次为：丙二醇(PG)＞氮酮(Azone),两者配伍使用有协同作用。结论 国民淀粉压敏胶、PVP K30、PG＋Azone分别作为分散型青蒿素贴剂的压敏胶、结晶抑制剂、促渗剂。 【关键词】 青蒿素；贴剂；压敏胶；结晶抑制剂；促渗剂 　　Abstract: Objective To determine the effect of pressure-sensitive adhesives, additives and penetration enhancers on the percutaneous absorption of artemisinin, and study on the formulation of artemisinin transdermal delivery systems. Methods The effects of various additives on the crystallization of artemisinin in polyacrylate adhesive matrix were investigated. The effects of pressure- sensitive adhesives, various additives and penetration enhancers on the in vitro permeation of artemisinin across SD rat abdominal skin were studied. Results National Starch polyacrylate pressure-sensitive adhesive was found to be the most efficient adhesive matrix. PVP-K30 significantly inhibited the crystallization of artemisinin in polyacrylate adhesive matrix. The enhancing effectiveness of the enhancers decreased in the order: PG＞Azone. PG combined with azone showed a higher synergic effect of enhancing effectiveness. Conclusion National Starch polyacrylate pressure-sensitive adhesive was the most effective pressure-sensitive adhesive matrix, PVP-K30 was the most effective crystallization inhibitor, PG combined with azone were the most effective penetration enhancers. 　　Key words：artemisinin；patch；pressure-sensitive adhesive；crystallization inhibitor；penetration enhancers 青蒿素具有退热快、原虫转阴时间短的特点,尤其适于抢救凶险型疟疾,但存在半衰期短、疟原虫易复燃等缺点。为了克服青蒿素半衰期短的缺点,我们将其制备成经皮给药缓释制剂。经皮给药制剂可避免肝脏的首过效应和对胃肠道的破坏、维持较长的作用时间、减少给药次数、维持恒定的有效血药浓度、降低药物毒性和不良反应、提高疗效等,在减少给药剂量的同时,大大降低疟原虫复燃率。本研究通过体外透皮试验对溶解型青蒿素贴剂的处方工艺进行了研究,为青蒿素贴剂的新药开发提供参考。 　　1 仪器与试药 Waters高效液相色谱仪；工作站：2695-2996版；泵：Waters2695四元泵；检测器：Waters2996紫外检测器；透皮扩散使用仪TK-20A,上海锴凯科技贸易有限公司；电子天平,美国Mettler Toledo AB135-S；甲醇为色谱纯,水为自制超纯水,其他试剂均为分析纯；青蒿素对照品,批号10