聚乙二醇负载葛根素前药的合成、表征及体外特性初步研究  

Synthesis,Characterization and Evaluation of Puerarin Prodrug in Vitro

作　　者：蒋福升[1] 刘霞[1] 王平[2] 谢捷[2] 余美荣[1] 金波[1] 丁志山[1] 

机构地区：[1]浙江中医药大学生命科学学院,杭州310053 [2]浙江工业大学药学院,杭州310014

出　　处：《中国药学杂志》2011年第7期522-526,共5页Chinese Pharmaceutical Journal

基　　金：浙江省自然科学基金资助项目(Y206776);浙江省中医药重点项目研究计划(2005Z001);浙江省教育厅科研项目(Y200805067);浙江省中医药青年课题研究计划(2009YB001);浙江工业大学重中之重学科开放研究基金

摘　　要：目的合成水溶性好,具有缓释特性并无溶血不良反应的葛根素前药。方法通过缩合反应以丁二酸为连接臂,将葛根素与单甲氧基聚乙二醇(Mr=5 000,mPEG5k)共价连接,制备聚乙二醇负载的葛根素前药,并通过TLC,UV,1H-NMR对其进行结构表征;同时测定葛根素前药的水溶性;考察前药在不同pH缓冲液中的释药特性;初步探索前药体外溶血特性。结果合成了聚乙二醇负载的葛根素前药,鉴定为预期产物。其水溶性较葛根素有较大提高;该前药在酸性的条件下稳定性较好,在pH 7.4的生理环境下能够缓慢持续的释药;体外抗溶血特性研究实验结果表明,该前药可避免葛根素的溶血性不良反应。结论与葛根素相比,前药水溶性好,并具有一定的缓释效果,而且可以避免溶血特性,有望成为新一代的葛根素制剂。OBJECTIVE To synthesize the prodrug of puerarin which has good water solubility,controlled release character and anhemolytic property.METHODS The puerarin prodrug was prepared by covalently linking puerarin to monomethoxy-polyethylene glycol（mPEG） via a butanedioic anhydride（DA） spacer,and the prodrug was verified by UV,FI-IR and 1H-NMR.The water solubility was determined.The drug release in different pH solutions and the hemolytic effect of the prodrug in vitro were evaluated.RESULTS The prodrug was synthesized and confirmed as expected products.The water solubility of the prodrug was improved dramatically;in addition,it was stable in low pH environment and could continuously release the active drug under physiological condition in vitro.Further more,the hemolytic study showed the prodrug could reduce the risk of hematotoxicity as often shown by puerarin.CONCLUSION Compar with puerarin,the prodrug shows better water solubility,sustained release behavior and absence of hematotoxicity.It can be a promising new drug.

关 键 词：葛根素 前体药物 聚乙烯二醇类 结构表征 溶血性 

分 类 号：R944[医药卫生—药剂学]