三七总皂苷胃肠道生物黏附片的体外释药及黏附特性考察

 目的考察三七总皂苷胃肠道生物黏附片中的总皂苷及主要单体皂苷的体外释药动力学、生物黏附片体外对离体家兔肠粘膜的黏附力。方法释放度测定按中国药典2000年版附录转篮法,采用显色法测定黏附片中三七总皂苷的释放,采用高效液相方法测定三七皂苷R₁,人参皂苷Rg₁,人参皂苷Rb₁的释放特征,分别用零级释放、一级释放模型、Higuchi方程P、eppas方程对4者的释放曲线进行动力学模拟,阐明其释药机制,并采用相似因子法判断各单体皂苷和总皂苷的释放曲线是否相似;采用自制的黏附力测试装置测定生物黏附片对兔肠粘膜的黏附力,对黏附力进行体外评价。结果三七总皂苷,三七皂苷R₁,人参皂苷Rb₁的释放符合Peppas方程,人参皂苷Rg₁的释放曲线符合一级释放动力学;相似因子法判断3种单体的释放曲线均与总皂苷的释放曲线相似。生物黏附片对肠粘膜的黏附力明显大于普通片(P<0.01)。结论三七总皂苷胃肠道生物黏附片中单体皂苷与总皂苷的释放机制不同,但释放曲线相似。生物黏附片对于肠粘膜具有较大的黏附力。

Evaluation of Adhesion and Release Kinetics of Panax Notoginseng Saponines Bioadhesive Tablets in vitro

OBJECTIVE To study the release kinetics of Panax Notoginseng Saponines(PNS) and various ginsenosides from gastrointestinal bioadhesive tablets,and to evaluate their bioadhesive force to rabbit small intestine in vitro.METHODS Using rotating basket method,the dissolubility was determined with water as dissolution medium at speed of 100 r·min^-1.The concentrations of PNS and three ginsenosides(notoginsenoside R₁,ginsenoside Rg₁ and ginsenoside Rb₁) were determined by coloration method and HPLC method respectively.To study the release mechanism of PNS and three ginsenosides,Zero order model,first order model,Higuchi equation and Peppas equation were used to simulate the dissolution curves.Similarity factor method was used to determine whether the release curves of PNS and three ginsenosides were similar.A self-made apparatus was used to compare the adhesive force between the bioadhesive tablets and regular tablets in rabbit small intestine in vitro.RESULTS The release kinetics of PNS,notoginsenoside R₁ and ginsenoside Rb₁ in bioahesive-tablets was discribed by Peppas equation,and the release kinetics of ginsenoside Rg₁ was fitted by first order model.The bioadhesion study showed that there were obvious differences between bioadhesive tablets and regular tablets in adherering to small intestine mucosa(P<0.01).CONCLUSION The release mechanism of PNS,notoginsenoside R₁,ginsenoside Rg₁ and ginsenoside Rb₁ in bioadhesive tablets are different,but their release curves are similar.The adhesive force of PNS bioadhesive tablets is stronger than that of regular tablets.