金雀花碱经皮给药系统的设计及评价  

Design and Evaluation of Transdermal Delivery Systems for Cytisine

作　　者：邢佳丽 刘灵 唐靖禹[2] 刘雨欣 赵利刚 XING Jiali;LIU Ling;TANG Jingyu;LIU Yuxin;ZHAO Ligang(School of Pharmacy,North China University of Science and Technology,Tangshan 063210;Dept.of Pharmacy,Tangshan Maternal and Child Health Hospital,Tangshan 063000;Tangshan Key Lab.of Novel Preparations and Drug Release Technology,Tangshan 063210)

机构地区：[1]华北理工大学药学院,河北唐山063210 [2]唐山市妇幼保健院药剂,河北唐山063000 [3]唐山市新型药物制剂与释药技术重点实验室,河北唐山063210

出　　处：《中国医药工业杂志》2024年第6期829-836,共8页Chinese Journal of Pharmaceuticals

基　　金：河北省自然科学基金资助项目——芳香族化合物丁香酚/肉桂醇脂肪酸酯促透剂的构建及作用机制研究(H2023209029);河北省青年拔尖人才项目;唐山市第七批市管优秀专家(2020091)。

摘　　要：通过促透剂单用及联用2种方案设计金雀花碱经皮给药系统,旨在提高金雀花碱的经皮促透量。采用卧式双室透皮扩散仪进行体外渗透试验,以筛选对金雀花碱透皮效果较好的促透剂,并通过体外释放试验和分子模拟技术初步探究该方案的促透机制。结果显示,香叶醇、薄荷醇以及二者分别与肉豆蔻酸异丙酯联用时,均有显著的促透效果(P<0.05);其中,5%香叶醇+5%肉豆蔻酸异丙酯联合应用时促透效果最佳,24 h经皮累积透过量是空白组的2.02倍。促透机制的初步研究表明,最佳促透剂组合通过增加金雀花碱贴剂的释放量及与神经酰胺的紧密结合而增大药物透过量。上述方法有望应用于金雀花碱贴剂的进一步研究与开发。Two research approaches(using penetration enhancers individually and in combination)were employed to develop a transdermal drug delivery system of cytisine,with the aim of increasing the transdermal penetration of cytisine.In vitro permeation experiments were conducted using a horizontal double-chamber diffusion cell to evaluate the optimal approach for enhancing cytisine penetration.The preliminary investigation on the transdermal mechanisms involved in the optimal approach was carried out through in vitro release experiments and molecular simulation methods.The results demonstrated that geraniol,menthol,and their combination with isopropyl myristate exhibited a significant enhancement in permeability(P<0.05).Among them,the best enhancement was observed in a system with a combination of 5%geraniol and 5%isopropyl myristate as the enhancers,resulting in a 2.02 times increase in cumulative penetration amount at 24 h compared with the blank group.The in vitro release experiments and molecular simulation revealed that the best combination of penetration enhancers could promote the release of cytisine from patches and bind to skin action sites,thus increasing the penetration of cytisine.This combination is expected to be used as a promising method for cytisine permeation in future investigations.

关 键 词：金雀花碱 促透剂 促透剂联用 体外渗透 促透机制 分子模拟 

分 类 号：R944.9[医药卫生—药剂学]