肉豆蔻酸单萜醇酯对布南色林经皮透过的影响  

Effects of Myristic Acid Monoterpene Alcohol Ester on Transdermal Permeation of Blonanserin

作　　者：张金伟 李翰铭 尹虹 邢佳丽 赵利刚 Zhang Jinwei;Li Hanming;Yin Hong;Xing Jiali;Zhao Ligang(School of Pharmacy,North China University of Science and Technology,Tangshan,063210;Tangshan Important Laboratory of Novel Preparations and Drug Release Technology,Tangshan,063210)

机构地区：[1]华北理工大学药学院,唐山063210 [2]唐山新型制剂与药物释放技术重点实验室,唐山063210

出　　处：《化学通报》2022年第7期853-859,共7页Chemistry

基　　金：河北省自然科学基金项目(H2019209254);华北理工大学杰出青年基金项目(JQ201713)资助。

摘　　要：本文以环状单萜醇α-萜品醇、L-薄荷醇及链状单萜醇香叶醇、香茅醇为先导化合物,采用酰氯酯化法合成肉豆蔻酸α-萜品醇酯(TER-C14)、肉豆蔻酸-L-薄荷醇酯(MEN-C14)、肉豆蔻酸香叶醇酯(GER-C14)和肉豆蔻酸香茅醇酯(CIT-C14),并考察单萜醇及其肉豆蔻酯作为促透剂对布南色林(Blo)的促透效果。通过体外经皮渗透实验、体外释放实验和分子模拟技术初步探究单萜醇及其肉豆蔻酯的促透机制。结果显示,当GER-C14或CIT-C14为促透剂时,均有显著的促透效果(P<0.05),并且24h经皮累积透过量是空白组的4.84倍和4.45倍。促透机制为肉豆蔻酸单萜醇酯破坏药物与神经酰胺之间的氢键相互作用,增加脂质迁移率和药物的自由能,从而促进药物的渗透。肉豆蔻酸单萜醇酯有望作为新型促透剂在经皮给药系统中广泛应用。In this paper, 2-(4-methylcyclohex-3-en-1-yl)propan-2-yl tetradecanoate(TER-C14),(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl tetradecanoate(MEN-C14),(E)-3,7-dimethylocta-2,6-dien-1-yl tetradecanoate(GER-C14) and 3,7-dimethyloct-6-en-1-yl tetradecanoate(CIT-C14) were synthesized by α-terpineol, L-menthol, geraniol, citronellol and myristic acid using acyl chloride esterification method. The penetration promoting activity of monoterpene alcohol and its myristate on blonanserin(Blo) was investigated, and its penetration mechanism was studied using in vitro release experiment and molecular docking technology. When GER-C14 or CIT-C14 was added, the accumulative 24 h premeation amount of Blo was 4.84 and 4.45 times of the enhancer-free control group, respectively. Mechanism research showed that myristic acid monoterpene alcohol ester disrupts the hydrogen bonding interaction between the drug and ceramide, increasing lipid mobility and the free energy of the drug, thereby promoting drug penetration. These myristates are expected to be widely used as a new type of penetration enhancer in transdermal drug delivery system.

关 键 词：肉豆蔻酸单萜醇酯 经皮给药系统 促透剂 促透机制 

分 类 号：TQ460.4[化学工程—制药化工]