穿心莲内酯衍生物ISA胆盐/磷脂混合胶束的制备及大鼠体内药动学研究  

Preparation of Andrographolide Derivative ISA-Loaded Bile Salt-Phosphatidy-I Choline-Mixed Micelles and Pharmacokinetics Evaluation in Rats

作　　者：焦文温[1] 张生杰[1] 张瑜[1] 高兴荣[1] 韩光[1] 

机构地区：[1]河南大学药物研究所,河南开封475004

出　　处：《中国药学杂志》2012年第20期1643-1648,共6页Chinese Pharmaceutical Journal

基　　金：河南省科技创新人才项目(094100510020)

摘　　要：目的制备ISA胆盐/磷脂混合胶束,并对其体外释放特性和大鼠体内药动学特征进行研究。方法采用薄膜水化法制备ISA胆盐/磷脂混合胶束,以星点设计-效应面法优化处方,透析法考察其体外释放行为,大鼠灌胃给药考察其体内药动学特征。结果优化所得ISA胆盐/磷脂混合胶束药物浓度为0.87 mg.mL-1,包封率为86.34%,载药量为4.87%,平均粒径为148.3 nm;经拟合ISA胆盐/磷脂混合胶束释放行为符合Rither-Peppas方程;药动学数据经房室模型拟合,ISA与ISA胆盐/磷脂混合胶束均符合二室模型,与原药组相比,胶束组吸收速度常数增加,达峰时间缩短,消除半衰期延长,分布体积减小,清除率降低,AUC增大,MRT延长。结论 ISA胆盐/磷脂混合胶束可增加药物溶解度,提高生物利用度。OBJECTIVE To prepare ISA-loaded bile sah-phosphatidylcholine-mixed micelles （ISA-BS/PC-MM） and study the release characteristics in vitro and pharmacokinetics in rats. METHODS ISA-BS/PC-MM were prepared by film dispersion method. The formulation was optimized by the central composite design-response surface method. The release behaviors in vitro of the micelles were studied by dialysis method and its pharmacokinetic characteristics were studied by intrastrie administration in rats. RESULTS The drug concentration, entrapment efficiency, drug loading and average diameter of the optimized ISA-BS/PC-MM were 0. 87 mg · mL-1 , 86. 34% , 4. 87% and 148.3 nm, respectively. The release characteristics of ISA-BS/PC-MM were well fitted with Rither-Peppas equation. The pharmacokinetic data of ISA and I-SA-BS/PC-MM were in accord with two-compartment model. Compared with the original drug, mieelles increased the absorption rate constant, shortened t prolonged the elimination half-life and MRT, reduced the volume of distribution and clearance rate, and increased AUC. CONCLUSION ISA-loaded bile salt-phosphatidy-lcholine-mixed mi- celles can increase drug solubility and enhance bioavailability.

关 键 词：ISA 混合胶束 星点设计 体外释放 药动学 

分 类 号：R969.1[医药卫生—药理学]