羟丙基-β-环糊精对甲氧苄啶包合过程研究  

Inclusion of trimethoprim with hydroxypropyl-β-cyclodextrin

作　　者：卢朝成[1] 符华林[1] 邹玉珠 张伟[1] 周涛[1] 金超[1] 罗莉[1] 曹航[1] 

机构地区：[1]四川农业大学动物医学院,动物疫病与人类健康四川省重点实验室,四川雅安625014 [2]重庆安格龙翔医药科技有限公司,重庆400039

出　　处：《计算机与应用化学》2014年第2期175-180,共6页Computers and Applied Chemistry

摘　　要：采用Chem3D Ultra 8.0和SYBYL进行分子模拟以及相溶解度法探讨羟丙基-β-环糊精对甲氧苄啶包合的可能性,在此基础上用溶剂搅拌法制备甲氧苄啶羟丙基-β-环糊精包合物;单因素实验考察有机溶媒浓度、主客分子物质的量比、温度、搅拌时间、搅拌速度、pH值对包合性能的影响;选择影响较大的因素进行正交实验,以甲氧苄啶的回收率、包合率和载药率为指标,优选出最优工艺条件;并采用薄层色谱法和差示扫描量热法对包合物进行表征和确认。结果表明甲氧苄啶能被羟丙基-β-环糊精包合;最优工艺为主客分子物质的量比为3:1,反应体系pH为7.5,搅拌时间为4 h;薄层色谱法和差示扫描量热法均验证了包合物的形成。甲氧苄啶包合物溶解度较甲氧苄啶原药增加约26倍。The complexation of trimethoprim （TMP） with hydroxypropyl-β-cyclodextrin （HP-β-CD） was studied. The feasibility of including TMP into the cavity of HP-β-CD was investigated by Chem3D Ultra 8.0 and SYBYL molecular simulation and phase solubility techniques, respectively. And then the Solution-stirring method was selected to preparation the Trimethoprim-hydroxypropyl-β-cyclodextrin inclusion complex （TMP-HP-β-CD）. Their yield, inclusion ratio, drug loading ratio effected by concentration of solvent, inclusion molar ratio of HP-β-CD to TMP, temperature, time, Stirring speed and pH value were studied. Complex formation was evaluated by thin layer chromatography （TLC） and differential scanning calorimetry （DSC）. The results showed that TMP able to be inclusion into HP-β-CD. The optimum process was obtained as： the molar ratio （HP-β-CD： TMP） =3：1, pH=7.5, time=4 h. TLC and DSC verify TMP-HP-β-CD inclusion complex formation. The results showed saturation solubility of TMP was increased up to 26 times by complexation with HP-β-CD （1.109±0.24 g/100 mL） compared with the unprocessed TMP （0.042±0.05 g/100 mL）.

关 键 词：甲氧苄啶 羟丙基-Β-环糊精 包合物 溶解度 

分 类 号：TQ015.9[化学工程]