氮酮对不同亲脂性中药有效成分的经皮促透作用研究

Percutaneous penetration enhancement effects of azone on TCM active ingredients with different lipophilicity

目的考察氮酮对不同亲脂性中药有效成分的经皮促透作用特征,探讨其对中药外用制剂中复杂成分的经皮促透效果。方法选择不同亲脂性中药有效成分,包括强亲脂性和强亲水性药物,即蛇床子素、川芎嗪、阿魏酸、葛根素、京尼平苷,采用体外透皮试验测定不同浓度氮酮对各药物的经皮促透吸收情况,并建立药物油水分配系数值(log Ko/w)与其对应促透倍数间的相关性。结果氮酮对不同亲脂性药物均表现出显著经皮促透作用,并呈现先随氮酮浓度增加而增强,达到一定浓度后其促透倍数开始下降的作用趋势;氮酮作用下药物log Ko/w值与促透倍数对数值呈抛物线关系,对log Ko/w值约为-0.5的药物具有最佳的经皮促透作用。结论氮酮对不同亲脂性中药有效成分均具有良好促透作用,且其促透倍数对数值与药物log Ko/w值呈抛物线关系。

Objective To investigate the effects of azone on transdermal absorption of TCM active ingredients with different lipophilicity,and further explore its percutaneous penetration enhancement effects on the complex TCM active ingredients. Methods Five model drugs,namely osthole,tetramethylpyrazine,ferulic acid,puerarin and geniposide,were selected based on their lipophilicity determined by log Ko / w,and then tested using in vitro permeation studies in which Franz diffusion cellsand rat skin were employed. Meanwhile,the association between the log Ko / wvalues of model drugs and enhancement ratio（ ER） was established. Results Different concentrations of azone could significantly promote the transdermal absorption of all model drugs. The ER value gradually increased with the increase of the azone concentration withina certain concentration range. It,however,started to decrease when exceedinga certain concentration level. The penetration enhancement ratio was roughly in parabolic curve relation with the drug lipophilicity after treatment with azone,and azone could achieve the optimal permeation effect for moderate hydrophilic drugs（ an estimated log Ko / wvalue of- 0. 5）. Conclusion azone could significantly promote the transdermal absorption of TCM components with different lipophilicity,and its penetration enhancement ratio was in parabolic curve relation with the drug lipophilicity.