淫羊藿苷在大鼠胃肠道内容物中的降解动力学研究

Study on the degradation kinetics of icariin in rat gastrointestinal contents

目的考察淫羊藿苷在大鼠胃肠道内容物中的稳定性与降解动力学特征,为淫羊藿苷口服制剂的开发及阐明淫羊藿苷的作用机制提供依据。方法制备大鼠胃内容物和各肠段内容物,采用HPLC法测定不同条件下匀浆液中淫羊藿苷的质量浓度。结果淫羊藿苷降解半衰期随肠道内容物质量浓度的升高而显著减小;淫羊藿苷在不同内容物中的代谢速率有差异,回肠、空肠、十二指肠、胃和结肠半衰期依次为0.83,1.26,2.81,18.48和87.72 h,降解速率常数依次为0.835 3 h^(-1),0.021 0 mL·μg^(-1)·h^(-1),0.018 3 mL·μg^(-1)·h^(-1),0.037 5 h^(-1)和0.007 9 h^(-1);其中十二指肠和空肠降解反应级数为二级,其余均为一级。结论淫羊藿苷在胃和结肠内容物中较稳定,易被小肠内容物降解。

Objective To research the oral preparation and elucidate the pharmacodynamic mechanism of icariin by investigating its degradation kinetics in gastrointestinal contents. Methods The contents of rat stomach and each intestinal segment were prepared,and the concentration of icariin in the contents was determined by HPLC. Results The half-life of icariin in the intestinal content was significantly reduced with increasing concentration.The metabolic rate of icariin was different in each content.The half-life periods were 0.83,1.26,2.81,18.48 and 87.72 h and the degradation rate constants were 0.835 3 h^-1 ,0.021 0 mL·μg^-1 ·h^-1 ,0.018 3 mL ·μg^-1 ·h^-1 ,0.037 5 h^-1 and 0.007 9 h^-1 in the contents of ileum,jejunum,duodenum,stomach and colon respectively.The degradation reactions of duodenal and jejunal were second-order reaction and the rest were first-order reaction. Conclusion Icariin is relatively stable in the contents of stomach and colon and is easily degraded by intestinal contents.