麝香酮对不同log P中药成分的经皮促透作用及其促透机制的初步研究

Enhancing effect and mechanism of muscone on transdermal penetration of traditional Chinese medicine ingredients with different log P value

为考察麝香酮对中药不同成分的促透作用,探究麝香酮的经皮促透作用机制。该研究以具有较大范围油水分配系数(log P)的中药成分蛇床子素、阿魏酸、栀子苷为模型药物,采用体外透皮实验研究麝香酮对模型药的经皮促透效果;测定模型药物的饱和溶解度、角质层/供给液分配系数,研究麝香酮对药物热力学活性以及药物向角质层分配的影响;采用衰减全反射-傅里叶变换红外光谱(ATR-FTIR)研究麝香酮对皮肤角质层分子结构的影响。结果显示,麝香酮可以显著提高不同脂溶性药物的经皮渗透,且随药物log P的减小其促透倍数增加,其促透作用机制主要是通过与角质层脂质的相互作用,扰乱脂质的堆积并增加脂质流动性,进而增加皮肤通透性促进药物的经皮吸收,为麝香酮在中药经皮给药制剂中的使用提供科学依据。

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action.The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values.The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC.Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR)was employed to explore the effect of muscone on the molecular structure of SC.The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs,and the enhancement ratio(ER)increased with the decrease in the log P.Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing,which improved skin permeability and promoted transdermal absorption of drugs.This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.