薄荷醇对不同logP值中药有效成分经皮吸收的促透研究

Effect of menthol on transdermal absorption of Chinese herbal medicinal ingredients with different log P values

目的:考察薄荷醇作为经皮促透剂对系列不同log P值(即油水分配系数)中药有效成分经皮促透作用,探讨其对复杂中药成分的经皮促透作用规律。方法:选择系列不同log P值中药有效成分作为模型药物,即蛇床子素(OT,log P=3.85)、川芎嗪(TMP,log P=2.34)、阿魏酸(FA,log P=1.26)、葛根素(PR,log P=-0.35)和京尼平苷(GP,log P=-1.01),采用体外透皮试验测定不同浓度薄荷醇对各模型药物的经皮促透作用,并根据药物log P值与其对应促透倍数建立相关性,总结并推测薄荷醇对复杂中药有效成分的经皮促透特征和规律。结果:1%浓度薄荷醇对系列模型药物未表现出明显的经皮促透作用。但是,当其应用浓度达到3%时,薄荷醇可显著促进不同log P值有效成分的经皮吸收,经皮促透效果较为明显,且呈浓度依赖性。相关性分析结果显示,在薄荷醇作用下,药物log P值与其对应促透倍数对数值呈良好负线性关系。同时,当药物log P值低于一定值(估计log P值约为-1^-0.5)后,其促透倍数开始表现出下降趋势。结论:适宜浓度的薄荷醇可有效促进不同log P值有效成分的经皮吸收,而对log P值较低的成分,其经皮促透效率更高。

Objective： To investigate the effect of menthol on the transdermal absorption of model drugs with different log P values,and understand its penetration-enhancing characteristics for complex Chinese herbal medicinal ingredients. Methods： A series of Chinese herbal medicinal ingredients were selected as model drugs based on their lipophilicity（ log P value）,namely osthole（ OT,log P = 3. 85）,tetramethylpyrazine（ TMP,log P =2. 34）,ferulic acid（ FA,log P = 1. 26）,puerarin（ PR,log P =- 0. 35） and geniposide（ GP,log P =- 1. 01）.The Franz diffusion cells were employed to investigate the effect of menthol on the transdermal permeation of these model drugs,and the relationship between log P values and enhancement ratio was established to obtain the information about the transdermal penetration-enhancing characteristics of menthol. Results： Menthol at the concentrationof 1% had no obvious effect on the transdermal absorption of the selected model drugs. However,menthol could significantly promote the transdermal permeation of all model drugs in a concentration-dependent manner when the application concentration was above 3%. Meanwhile,the relationship analysis revealed that log P values had remarkable negative linear relationship with the logarithm of penetration enhancement ratio,suggesting that menthol exhibited higher efficiency for the active drugs with relative low log P value. In addition,the studies also showed the transdermal penetration ratio appeared to start to decline when the log P value was lower than a certain value（ an estimated log P value of- 1 -- 0. 5）. Conclusion： Menthol of proper concentration can significantly facilitate the transdermal permeation of the model drugs with different log P values,and exhibits better penetration efficiency for active drugs with relative low log P values.