鬼臼毒素油/水分配系数测定及羟丙基-β-环糊精对其增溶作用研究  

Determination of Oil-Water Partition Coefficient and Solubilization of Hydroxypropyl-β-cyclodextrin on Podophyllotoxin

作　　者：韩立炜[1] 张丽芳[2] 杜守颖[1] 韩志东[3] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]国家知识产权局专利审查协作中心,北京100083 [3]天津红日药业股份有限公司,天津301700

出　　处：《中国实验方剂学杂志》2011年第10期11-15,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：科技部"重大新药创制"科技重大专项(2009ZX09502-008)

摘　　要：目的:考察室温下不同pH介质中鬼臼毒素的油水分配系数以及羟丙基-β-环糊精对鬼臼毒素的增溶作用。方法:采用摇瓶法测定鬼臼毒素在不同pH介质中的溶解度和油水分配系数;采用正交设计试验优选羟丙基-β-环糊精包合鬼臼毒素的最佳工艺;以相溶解度法考察羟丙基-β-环糊精对鬼臼毒素的增溶作用。结果:鬼臼毒素在水中溶解度为0.09 g.L-1,在正辛醇中的溶解度为12.91 g.L-1。在水和正辛醇两相中5 min即可达到分配平衡,油水分配系数P=179.067,疏水常数logP=2.249。相溶解度图属于AL型,包合常数为1 022.65 L.mol-1。结论:鬼臼毒素亲脂性较强,在油水两相分配平衡快;羟丙基-β-环糊精对鬼臼毒素具有很好的增溶作用,且可与之形成较稳定的包合物。Objective：To determine the oil-water partition coefficients of podophyllotoxin at variable pH and to assess the solubilizing effect of 2-hydroxypropyl-β-cyclodextrin（HP-β-CD） on podophyllotoxin.Method： The water solubility and oil-water partition coefficient of podophyllotoxin in different pH media were determined using the shake-flask method.The inclusion processes with HP-β-CD were optimized through orthogonal design.The solubilization effect of HP-β-CD on podophyllotoxin was investigated by a phase-solubility method.Result： The solubility of podophyllotoxin in water was 0.09 g·L-1,while the solubility in octanol was 12.91 g·L-1.The distribution of podophyllotoxin between water and octanol could be achieved balance in 5min.The oil-water partition coefficient（P） of podophyllotoxin was 179.067,so logP was 2.249.The phase solubility diagram was AL-type,and the inclusion constant（K） was 1 022.65 L·mol-1.Conclusion： Podophyllotoxin is high lipophilic,and distributes to be balanced rapidly between water and oil.The HP-β-CD has good solubilization effect on podophyllotoxin,which forms stable inclusion complexes with podophyllotoxin.

关 键 词：鬼臼毒素 油/水分配系数 羟丙基-Β-环糊精 包合 相溶解度 增溶 

分 类 号：R283.6[医药卫生—中药学]