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目的:本研究以α-萜品醇为先导化合物与饱和直链脂肪酸合成系列萜品醇酯衍生物,包括:丁酸萜品醇酯(T-BUT)、己酸萜品醇酯(T-HEX)、庚酸萜品醇酯(T-HEP)、癸酸萜品醇酯(T-DEC)、月桂酸萜品醇酯(T-DOD)、肉豆蔻酸萜品醇酯(T-TET)、硬脂酸萜品醇酯(T-STE)、油酸萜品醇酯(T-OA),并考察d-萜品醇酯类衍生物对美洛昔康(MLXC)的促透活性.方法:采用双室扩散池以离体兔皮为屏障进行体外渗透实验,系统考察了合成萜品醇酯及常用促透剂[N-甲基吡咯烷酮(NMP)、月桂氮卓酮(agone)、薄荷醇(M)]在肉豆蔻酸异丙酯(IPM)系统和压敏胶型贴剂系统中对MLXC渗透行为的影响.结果:与不加促透剂(空白)相比,浓度为5％的0α-萜品醇,T-BUT,T-HEX,T-HEP,M及NMP对MLXC均有显著的促透作用(P＜0.05);与萜品醇相比,NMP和T-HEX的促渗作用均显著提高(P＜0.05);而制成压敏胶分散型(DIA)贴剂后,仅α-萜品醇,T-HEX,M,NMP表现出促透作用(P＜0.05),当5％ NMP与5％ T-HEX联用时,MLXC的8h累积透过量是空白组的5.08倍.结论:合成的0α-萜品醇脂肪酸酯对MLXC有显著促透作用,有望成为一种有应用价值的促透剂.“,”Objective:To develop O-acylterpineol derivative as transdermal penetration enhancers for meloxican (MLXC),including 2-(4-methylcyclohex-3-en-l-yl) propan-2-yl butanoate (T-BUT),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl hexanoate (T-HEX),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl heptanoate (T-HEP),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl decanoate (T-DEC),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl dodecanoate (T-DOD),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl tetradecanoate (T-TET),2-(4-methylcyclohex-3-en-l-yl)propan-2-yl stearate (T-STE) and (E)-2-(4-methylcyclohex-3-en-l-yl) propan-2-yl octadec-9-enoate (T-OA).Methods:The compounds were synthesized by using α-terpineol and fatty acid.The in vitro permeation studies of MLXC were conducted in isopropyl myristate(IPM) solution or from patches in side-by-side diffusion cells,and the enhancing effects of O-acylterpineol,l-menthol,azone and N-methylpyrrolidone(NMP) on the permeation behavior of MLXC were also investigated.Results:The results of in vitro permeation experiment showed that the compounds including 5 ％ terpineol,5 ％ T-BUT,5％ T-HEX,5 ％ T-HEP,5 ％ menthol and 5 ％ NMP had significant enhancing effects on the penetration of MLXC compared with the control(P ＜ 0.05),additionally,NMP and T-HEX had higher penetration activity than terpineol(P ＜ 0.05).While in the DIA patches only α-terpineol,menthol,T-HEX and NMP could promote the penetration of MLXC.The combination of 5％ NMP and 5％ T-HEX could provide the largest penetration amount of MLXC within 8 h (5.08-fold) compared with the control group (P ＜ 0.05).Conclusion:O-acylterpineol derivatives have significant promoting effects on the penetration of MLXC,which indicates that O-acylterpineol might be a promising enhancer.