茴三硫磷脂复合物的制备及其体内外评价Preparation of anethol trithione-phospholipid complex and studies on its pharmacokinetics in rats
姚婷婷,甘勇,韩思飞,朱春柳,胡申烨,潘卫三
YAO Ting-ting1,2,GAN Yong2,HAN Si-fei2,ZHU Chun-liu2,HU Shen-ye3
摘要(Abstract)：
目的制备茴三硫磷脂复合物,对比评价茴三硫磷脂复合物和市售胶囊在大鼠体内的药动学特征及口服生物利用度。方法采用溶剂挥发法制备茴三硫磷脂复合物,并对复合物进行红外、体外溶出度及体外消化实验的考察;SD大鼠口服分别给予茴三硫磷脂复合物和市售胶囊后,采用RP-HPLC法检测不同时间大鼠体内茴三硫及其代谢物对羟基茴三硫的浓度,通过DAS2.0程序计算药代动力学参数。结果红外图谱验证了复合物的形成;与市售制剂相比,形成的磷脂复合物改善了药物的溶出,降低了药物在模拟消化液中的沉淀率,提高了药物的溶解度;以茴三硫市售胶囊做参比制剂,口服茴三硫磷脂复合物后原型物与代谢物的主要药动学参数均发生一定程度改变;其中磷脂复合物的原型物与代谢物的AUC0-∞分别为1 270.08μg.h.L-1和4 001.31μg.h.L-1,而市售胶囊分别仅为573.21μg.h.L-1和1 348.64μg.h.L-1。结论将茴三硫制备成磷脂复合物后,可以改善药物的口服吸收,显著提高茴三硫的口服生物利用度。
Objective To prepare anethol trithione-phospholipid complex and compare the bioavailability and pharmacokinetic characteristics after oral administration of anethol trithione-phospholipid complex and commercial capsules in rats.Methods Digestion in vitro and IR properties of the complex was investigated.The concentration of parent drug and its metabolite after administration of anethol trithione-phospholipid complex and commercial capsules at different time in rats were determined by HPLC.The pharmacokinetic parameters were computed by software program DAS 2.0.Results The IR results proved that the complex was formed.Compared with the commercial capsules,the drug's dissolution was improved and its digestion precipitation rate in vitro was decreased by changing into the phospholide complex.The drug solubility in gastrointestinal tract was remarkably increased by making the preparation.And the capital pharmacokinetic parameters of the complex were changed,the AUC0-∞ of the parent drug and its metabolite of the complex were 1270.08 and 4 001.31 μg·h·L-1,respectively.Conclusions It is concluded that after oral administration of anethol trithione-phospholipid complex in rats,the bioavailability of anethol trithione is increased greatly.This is mainly due to an obvious improvement of the oral administration absorption.
关键词(KeyWords)：
茴三硫;磷脂复合物;药动学
anethol trithione;phospholipid complex;pharmacokinetics
基金项目(Foundation):
作者(Author):
姚婷婷,甘勇,韩思飞,朱春柳,胡申烨,潘卫三
YAO Ting-ting1,2,GAN Yong2,HAN Si-fei2,ZHU Chun-liu2,HU Shen-ye3
DOI: 10.14066/j.cnki.cn21-1349/r.2010.03.010
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