通栓救心pH依赖型缓释胶囊在犬体内的药动学和药效学研究

目的制备通栓救心pH依赖型缓释胶囊，并进行犬体内药动学和药效学的研究。方法以牡丹皮、川芎、香附的超临界CO2萃取物及冰片为原料，经β—CD包合固化后用粉末层积法制备含药微丸，分别用HPMC、Eudragit L-30D-55、Eudragit L100-S100（1：5）包衣制备pH依赖型延迟释药微丸，将延迟类型不同的包衣微丸按预设剂量分别混合填充胶囊，制得通栓救心pH依赖型缓释胶囊。采用血药浓度法测定方剂中指标性成分丹皮酚的血药浓度，研究其药动学；采用血清药理学方法研究其药效学。结果血药浓度测定法表明通栓救心pH依赖型缓释胶囊和通栓救心片的体内平均滞留时间分别为8．04、2．89h，相对生物利用度为126．3％。药效学研究结果表明两者的平均效应维持时间分别为11．27、5．94h，相对生物利用度为129．1％。结论通栓救心片在体内具有吸收快、消除快和作用维持时间较短的特点，而通栓救心pH依赖型缓释胶囊在体内有起效迅速、药效持久、缓释的特点。

Pharmacokinetics and pharmacodynamics of Tongshuan Jiuxin pH-Dependent Delayed-release Capsula in dogs in vivo

Objective To prepare Tongshuan Jiuxin pH-Dependent Delayed-release Capsula and study its pharmacokinetics and pharmacodynamics in dogs in vivo. Methods Borneol and the extracts of Cortex Moutan,Rhizoma Chuanxiong, and Rhizoma Cyperi prepared by COZ supercritical fluid extraction method were solidified or included withp-cyclodextrin.Pellets were prepared by means of powder layering with the solidified extracts and borneol.The pH-dependent delayed-release pellet system was prepared by coating with HPMC,Eudragit L-30D-55,and Eudragit L100-S100 (15)combinations,respectively.Tongshuan Jiuxin pH-Dependent Delayed-release Capsula was prepared by mixing the three kind of pellets at the ratio of 1,11.The concentration of paeonol in plasma was determined by HPLC and the pharmacodynamic parameters were evaluated by serum pharmacology method. Results The results from the paeonal concen-tration in plasma showed that the mean residence time Conclusion Tongshuan Jiuxin Tablet has the characteristics of rapid absorption,-qucik elimination,and shorter action-maintaining time.Whereas Tongshuan Jiuxin pH Dependent Delayed-release Capsula has the characteristics of rapid absorption,prolonged and relaxed effective action compared with Tongshuan Jiuxin Tablet.