摘要
以米托蒽醌为模型药物，用乳化热固化法制备了米托蒽醌白蛋白微球。以D-半乳糖为原料，经溴代、缩合、置换、加成等反应合成了2-亚氨基-2-甲氧基乙基-1-硫化-β-D-半乳吡喃糖苷（IME－thiogalactose）。以此为中间体与米托蒽醌白蛋白微球在室温下反应制备了联糖米托蒽醌白蛋白微球及其冻干剂。并对冻干剂的形态、球径及其分布、再分散性、糖密度、载药量、体外释药特性进行了研究，为白蛋白微球与联糖白蛋白微球在体内的肝靶向性探讨奠定了基础。
Bovin serum albumin microspheres loaded mitoxantrone(DHAQ-BSA-MS)were prepared by an emulsion-heat stabilization technique.2 imino2-methoxyethyl-thiogalactose(IME-thiogalactose)was synthesized by bromization,condensation, substitution and addition of D-galactose.Subsequently, galactosyl-DHAQ-BSA-MS(Gal-DHAQ-BSA-MS)were prepared by the convalent coupling of IME- thioga-lactose to DHAQ-BSA-MS at room temperature. Then, Gal-DHAQ-BSA-MS was lyophilized and its morphology, size and distribution, redispersion, carbohydrate density, drug loading and the characteristic of the release test in vitro were studied. The results showed that the surface of GalDHAQBSA-MS was coated with a thin film. Its diameter range from 0. 497μm to 3. 71μm with a mean diameterof about 1. 342μm. The lyophilization had a good redispersion after dispersing injection water, the mean carbohydrate density and drug loading among three batches were 34% and 3.044%, respectively. The release of DHAQ from the carrier at the initial phase could be described by Higuchi equation:Q=0. 05461 +0. 1859 (r=0. 9993); the terminal phase could be simulated by first-order process: Q=1- 0. 7265 e-3.875×10-3 (r=0. 9999), the release provides a base for the study of the liver targeting effect in vivo of DHAQ-BSA-MS and Gal-DHAQ-BSA-MS.
出处
《华西药学杂志》
CAS
CSCD
北大核心
1998年第4期217-222,共6页
West China Journal of Pharmaceutical Sciences
基金
国家自然科学基金!39670862
关键词
米托蒽醌
白蛋白微球
制备
微球联糖
体外释放
Galactosyl-mitoxantrone-bovin serum albumin-microspheres
Drug release in vitro
Liver targeted drug delivery system
IME-thiogalactose
