乌头碱、人参皂苷Rg_1与延胡索乙素经皮渗透及协同促渗研究

Study on Percutaneous Absorption and Synergistic Penetration Enhancement Effect of Aconitine,Ginsenoside Rg_1 and Tetrahydropalmatine

目的研究乌头碱、人参皂苷Rg1与延胡索乙素的透皮吸收及其相互间经皮渗透的影响。方法采用PermcellKH-5P型横式扩散池分别进行全皮和去角质层皮肤的体外透皮实验,用高效液相色谱法测定乌头碱、人参皂苷Rg1与延胡索乙素的累积透过量,并计算出它们的经皮渗透动力学参数。测定有效成分的油水分配系数(LogP),考察2种及3种有效成分组合的透皮行为及相互影响。结果乌头碱、人参皂苷Rg1与延胡索乙素在全皮中的扩散系数分别为123.95、50.32、96.25(×10-10cm2/s),在活性表皮中的扩散系数分别为539.00、93.60、354.70(×10-10cm2/s),LogP依次分别为1.66、0.66、0.57。在3种有效成分共存的体系中,三者的累积透过量出现64%～293%不同程度的提高。结论3种有效成分合用对经皮吸收会产生协同促进作用,其中乌头碱与人参皂苷Rg1间的经皮协同促渗作用最明显。

Objective To study percutaneous absorption kinetics and synergistic penetration enhancement of tetrahydropalmatine, aconitine and ginsenoside Rg1. Methods The in vitro intact and stripped skin permeation experiments were carried out by using Permcell KH-SP horizontal proliferation system. The percutaneous kinetic parameters of tetrahydropalmatine, aconitine and ginsenoside Rg1 were determined by HPLC, and the transdermal behaviors of the three active ingredients and interactions of combination were investigated. Result The cumulative amounts in 24 h of intact skin of tetrahydropalmatine, aconitine and ginsenoside Rgl were 123.95, 50.32, 96.25 （× 10^-10 cm^2/s）. The cumulative amounts in 24 h of stripped skin of them were 539.00, 93.60, 354.70 （×10^-10 cm^2/s）. The LogP were 1.66, 0.66 and 0.57 respectively. Each component had cumulated amount permeated of improvement by 64%-293% in coexistence system of three active ingredients. Conclusion The combination of three active ingredients results in a synergistic enhancement effect on percutaneous absorption of every active ingredient, and it is shown that the maximal enhancement effect appears between aconitine and ginsenoside Rg1.