溶液系统中单萜醇酯类促透剂对茶碱经皮渗透的影响  

Effect of Monoterpene Alcohol Esters as Permeation Promoters in Solution Systems on Transdermal Penetration of Theophylline

作　　者：逯新坤 刘慧杰 张金伟 张志兰 魏文静 赵利刚 LU Xinkun;LIU Huijie;ZHANG Jinwei;ZHANG Zhilan;WEI Wenjing;ZHAO Ligang(School of Pharmacy,North China University of Science and Technology,Tangshan 063210;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》2023年第6期919-926,共8页Chinese Journal of Pharmaceuticals

基　　金：河北省“第三批青年拔尖人才”项目。

摘　　要：采用酰氯法以单萜醇[α-萜品醇(TER)、L-薄荷醇(MEN)、香叶醇(GER)和香茅醇(CIT)]作为先导化合物与脂肪酸[庚酸(C7)、肉豆蔻酸(C14)、硬脂酸(C18)和油酸(dC18)]反应合成系列脂肪酸单萜醇酯衍生物。以离体兔皮为屏障,利用水平卧式双室扩散池进行体外渗透试验,考察单萜醇及其系列单萜醇酯衍生物对肉豆蔻酸异丙酯(IPM)溶液中茶碱(1)体外渗透行为的影响。与空白组(不加促透剂)相比,α-萜品醇庚酸酯(TER-C7)、L-薄荷醇庚酸酯(MEN-C7)、香叶醇油酸酯(GER-dC18)、香茅醇油酸酯(CIT-dC18)对1均有显著促透效果(P<0.05)。在所探究的环状单萜醇酯中,MEN-C7对1的促透效果最佳;在受试的链状单萜醇酯中,GER-dC18对1的促透效果最佳。上述2组中1的8h累积透过量分别是空白组的3.02和1.86倍。环状及链状单萜醇酯衍生物对1均有显著促透效果,其中环状单萜醇酯MEN-C7的促透效果更优,有望用于经皮给药制剂的开发。A series of fatty acid monoterpene alcohol ester derivatives were synthesized via chlorination reaction of monoterpene alcohols[α-terpineol(TER),L-menthol(MEN),geraniol(GER) and citronellol(CIT)],as lead compounds,and fatty acids[heptanoic acid(C7),myristic acid(C14),stearic acid(C18) and oleic acid(dC18)].The in vitro permeation experiments were conducted with horizontal double chamber diffusion cell and excised rabbit skin as a skin barrier.The effects of the monoterpene alcohols and their monoterpene alcohol ester derivatives on in vitro permeation behavior of theophylline(1) in the isopropyl myristate(IPM) solutions was investigated.Compared with the blank group(without any permeation promoter),α-terpinol heptanoate(TER-C7),L-menthol heptanoate(MEN-C7),geraniol oleate(GER-dC18) and citronellol oleate(CIT-dC18) showed significant permeation promoting effects on 1(P0.05).Among the cyclic monoterpene esters explored,MEN-C7 showed the best permeation promoting effect on 1.While among the tested chain monoterpene esters,GER-dC18 showed the best permeation promoting effect on 1.The cumulative permeation amount of 1 at 8 h of above two groups were 3.02 and 1.86 times higher than that of the blank group,respectively.Both cyclic and chain monoterpene alcohol ester derivatives showed significant permeation promoting effects on 1.Among which the cyclic monoterpene alcohol ester,MEN-C7,had the superior permeation promoting effect and was promised practical use in future transdermal application.

关 键 词：茶碱 促透剂 单萜醇酯 体外渗透 分子模拟 

分 类 号：R944.9[医药卫生—药剂学]