文献类型：期刊文献

中文题名：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

英文题名：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：[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

年份：2013

卷号：44

期号：2

起止页码：171

中文期刊名：中国医药工业杂志

外文期刊名：Chinese Journal of Pharmaceuticals

收录：CSTPCD;;北大核心:【北大核心2011】；CSCD:【CSCD2013_2014】；

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

语种：中文

中文关键词：难溶性药物;BMCP25;二甲基--环糊精;包合物;表征;药动学

外文关键词：water insoluble drug; BMCP25; 2,6-di-O-methyl-β-cyclodextrin; inclusion; characterization;pharmacokinetics

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.