难溶性药物BMCP25二甲基-β-环糊精包合物的表征及在大鼠体内的药动学  

Characterization and Pharmacokinetics of Dimethyl-β-cyclodextrin Inclusion Complexes of Water Insoluble Drug BMCP25 in Rats

作　　者：陈水娟[1] 付栋君[1] 高姗姗[1] 高峰[1,2,3] 左建平[4] 

机构地区：[1]华东理工大学药学院药剂教研组,上海200237 [2]华东理工大学上海市新药设计重点实验室,上海200237 [3]华东理工大学上海市功能性材料化学重点实验室,上海200237 [4]中国科学院上海药物研究所新药研究国家重点实验室,上海201203

出　　处：《中国医药工业杂志》2013年第2期171-174,共4页Chinese Journal of Pharmaceuticals

基　　金：上海市科学技术委员会项目资助(11DZ2260600和10DZ2220500)

摘　　要：采用研磨法制备难溶性药物BMCP25(1)-二甲基--环糊精(DM--CD)包合物。X射线衍射及扫描电镜结果提示1经包合后,由针状结晶转变为无定形,形成了新的物相。包合后,1溶解度从(0.36±0.08)g/ml提高至(123.82±9.81)g/ml。建立了大鼠血浆中1的HPLC测定法,考察大鼠静脉注射1混悬液(2 mg/kg)及灌胃给予1混悬液或1-DM--CD溶液(10 mg/kg)的药动学情况。结果表明,1混悬液灌胃给药组的大鼠血浆中药物浓度低于最低检测限,而1-DM--CD包合物的口服生物利用度为(16.84±5.88)%。可见1-DM--CD包合物可显著改善口服生物利用度。The inclusion complexes of a water insoluble drug BMCP25 （1） with 2,6-di-O-methyl-β- cyclodextrin （DM-13-CD） were prepared by grinding method. The results of X-ray diffraction and scanning electron microscopy indicated that the drug in inclusion was changed to amorphous phase from the needle-like crystalline phase. The solubilities of 1 before and after inclusion were （0.36±0.08） and （123.82±9.81） μg/ml. An HPLC method was established for the determination of 1 in rat plasma. The pharmacokinetics of 1 in rats after iv administration （2 mg/kg） of 1 suspension or ig administration （10 mg/kg） of 1 suspension or its inclusion solution were investigated. After ig administration, the drug concentration in rat plasma was below the limit of detection in the 1 suspension group, while the oral bioavailability of 1-DM-β-CD inclusion complexes was （16.84±5.88） %. It indicated that the 1-DM-β-CD inclusion complexes could significantly enhance oral bioavailability of 1.

关 键 词：难溶性药物 BMCP25 二甲基--环糊精 包合物 表征 药动学 

分 类 号：R944.9[医药卫生—药剂学]