复方配伍对三七总皂苷生物药剂学性质的影响

Effects of Compound Compatibility on Biopharmaceutical Characteristics of Panaxnotoginseng Saponins

目的:研究复方配伍对三七总皂苷(PNS)的胃肠道稳定性、膜渗透性及脂溶性的影响。方法:建立PNS中主要成分人参皂苷Rg1和Rb1含量的HPLC测定方法;考察PNS单方和PNS+丹参醇提物+冰片三联复方在人工胃肠液中孵育后两成分的稳定性;采用大鼠在体单向灌流模型,测定PNS单方、PNS+冰片二联方、PNS+丹参醇提物二联方和三联复方中两成分的表观渗透系数(Papp);并测定各方中两成分的油水分配系数(P)。结果:在人工胃液中孵育3小时后,单方和三联复方中Rg1和Rb1含量均下降80%以上,且与单方相比,复方中Rg1和Rb1的降解半衰期分别有所缩短和延长,但均无显著性差异(P>0.05);在人工肠液中孵育24小时后,单方和复方中两成分的相对含量均维持在90%以上。PNS与冰片配伍后,Rg1和Rb1的Papp值显著提高,分别为单方的2.56和1.58倍(P<0.05);而与丹参醇提物配伍后,两成分的Papp值也有所提高,但无显著性差异(P>0.05);三联复方中两成分的Papp值则分别为单方的4.87和2.33倍,具有显著性差异(P<0.05)。与单方相比,PNS的任何二联和三联复方中两成分的P值均有所提高,但无显著性差异(P>0.05)。结论:复方配伍可提高PNS的膜渗透性和脂溶性,促进其口服吸收,但并不能改善其胃肠道稳定性。

Objective： To investigate the effects of compound compatibility on the stability in gastrointestinal tract, membrane permeability and lipophilicity of panaxnotoginseng saponins （PNS）. Methods： HPLC method was established to determine the contents of ginsenoside Rgl and Rbl, the two main constituents of PNS. The stability of Rgl and Rbl in simple PNS and PNS ＋ borneol ＋ Salvia alcohol extract triple compound recipes in artificial gastrointestinal juice was examined. The rat in situ single pass perfusion model was used to measure the apparent membrane permeability （Papp） values of Rgl and Rbl in simple PNS, PNS ＋ borneol compound, PNS ＋ Salvia alcohol extract compound and PNS ＋ borneol ＋ Salvia alcohol extract compound recipes. The oil/water partition coefficient （P） values of Rgl and Rbl in the different recipes wene also determined. Results： The contents of both Rgl and Rbl in simple PNS and triple compound recipes decreased by more than 80% after being incubaled in artificial gastric juice for 3 h, and compared with simple PNS recipe, the degradation half-times of the two constituents in triple compound recipe were shortened or prolonged with no significant difference （P 〉 0.05）. The relative contents of the two constituents in simple PNS and triple compound recipes kept more than 90% after being incubated in artificial intestinal juice for 24 h. The P^pp values of Rgl and Rbl in PNS ＋ borneol compound recipe and in triple compound recipe significanlty increased respectively 2.56 and 1.58 times and 4.87 and 2.33 times as great as those in simple PNS recipe （P 〈0.05）, and the Papp values of the two constituents in PNS ＋ Salvia alcohol extract compound recipe increased with no significant difference compared with those in simple PNS recipe （P 〉 0.05）. The P values of the two constituents in all compound recipes increased with no significant differente compared with those in simple PNS recipe （P 〉 0.05）. Conclusion： The membrane permea- bility and lipophilicity of PNS could be increased so as to improve its oral absorption, however, its stability in gastrointestinal tract couldn＇t be improved, with compound compatibility.