手性薄荷醇酯衍生物对氟比洛芬经皮促渗透作用的考察

Effect of Chiral O-Acylmenthol Derivatives on in vitro Permeation of Flubiprofen

分别以薄荷醇手性对映体(d-薄荷醇、l-薄荷醇)为先导化合物合成其脂肪酸酯衍生物:薄荷醇癸酸酯(l-M-DEC、d-M-DEC)和薄荷醇月桂酸酯(l-M-DOD、d-M-DOD)。采用卧式双室扩散池,以离体兔皮为屏障进行体外渗透试验,考察了合成得到的手性薄荷醇酯衍生物在肉豆蔻酸异丙酯(IPM)系统和压敏胶型贴剂系统中对氟比洛芬(1)渗透行为的影响。结果表明在IPM系统中,各促透剂在浓度3%时对1均有显著的促透作用(P<0.05);而制成压敏胶(Duro-Tak 87-4098)分散型贴剂后,各促透剂对1同样有显著的促透作用(P<0.05),对1促透作用由大到小依序为:d-M-DOD>l-MDOD>d-M-DEC>l-M-DEC>d-薄荷醇>l-薄荷醇。结果显示,手性薄荷醇酯衍生物在IPM系统和压敏胶贴剂系统中对1均有良好的促透作用。

The aim of this paper was to investigate the penetration effect of chiral O-acylmenthol derivatives, including 2-isopropyl-5-methylcyclohexyl decanoate （l-M-DEC, d-M-DEC） and 2-isopropyl-5-methylcyclohexyl dodeconoate （I-M-DOD, d-M-DOD）, on permeation behavior of flubiprofen （FP） in the isopropyl myristate （IPM） system and the dug-in-adhesive （DIA） patches. The in vitro percutaneous permeability test was carried out with twochamber cells and excised rabbit skin as the barrier. The results showed that all enhancers at 3 % had significant enhancing effects on the penetration of FP in the IPM system compared with the blank control （P〈0.05）. In the DIA patches with Duro-Tak 87-4098 pressure sensitive adhesive, all enhancers could also promote the penetration activity compared with the blank control （P〈0.05）, and the promoting effects were in the following order of d-M-DOD〉l-M-DOD〉d-M-DEC〉l- M-DEC〉d-menthol〉l-menthol. FP could penetrate the rabbit skin well with O-acylmenthol derivatives as the penetration enhancers in both the IPM system and the DIA patches.