Kitagawa S, Li H, Sato S
Niigata College of Pharmacy, Japan.
Chem Pharm Bull (Tokyo). 1997 Aug;45(8):1354-7. doi: 10.1248/cpb.45.1354.
Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability of coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butyl paraben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of hydrophilic paraben.
研究了对羟基苯甲酸甲酯、乙酯、丙酯和丁酯通过切除的豚鼠背部皮肤的透皮情况，并观察了渗透促进剂l-薄荷醇加乙醇本身以及N-十二烷基-2-吡咯烷酮的作用。对羟基苯甲酸酯的渗透系数与正辛醇/水分配系数相关。在15%乙醇中添加1% l-薄荷醇可使对羟基苯甲酸甲酯的渗透系数增加约16倍，而该促进剂可使对羟基苯甲酸丁酯的渗透系数降至对照值的约五分之一。对于15%乙醇本身的作用也观察到了类似但较弱的趋势。0.025%的N-十二烷基-2-吡咯烷酮悬浮液可使对羟基苯甲酸甲酯的渗透系数增加约7倍，而对羟基苯甲酸丁酯的渗透系数没有明显变化。因此，在该化合物存在下，对羟基苯甲酸酯的渗透系数对正辛醇/水分配系数的依赖性几乎消失。对角质层脂质脂质体的自旋标记研究表明，这些渗透促进剂使脂质双层流动性的增加与其对对羟基苯甲酸甲酯皮肤渗透的增强作用相对应。角质层脂质片层的扰动似乎与其对亲水性对羟基苯甲酸酯吸收的增强有关。
