麦冬多糖MDG-1聚乙二醇修饰物的合成和药动学的研究.pdfVIP

麦冬多糖MDG-1 聚乙二醇修饰物的合成与药动学研究 1,2 2 1 1,2 2,3 1,2 林晓 ，姜艳 ，王卓君 ，冯怡 ，徐德生 ，沈岚 （1. 上海中医药大学 中 药学院，上海 201203 ；2. 上海中医药大学 中药现代制剂技术教育部工程研究中心，上海 201203 ；3. 上海曙光医院，上海200021 ） 摘要:目的 探索通过聚乙二醇修饰技术以改善麦冬多糖MDG- 1的药动学性质。 方法 以氨基聚乙二醇单甲醚作为修饰剂，研究聚乙二醇修饰MDG- 1的合成反应 条件，用高效凝胶色谱法测定修饰物的分子量与接枝率，并考察其药动学性质。 结果 确定了优化的合成条件，制得多种用不同分子量聚乙二醇修饰的具有不同 接枝率的MDG- 1聚乙二醇修饰物，其生物半衰期较原药有明显的延长，延长程 度与修饰剂的分子量和修饰物的接枝率有关。结论 聚乙二醇修饰技术是一个具 有进一步研究前景的改善MDG- 1药动学性质的方法。 关键词：麦冬；多糖；聚乙二醇；药动学；生物半衰期 Study on Synthesis and Pharmacokinetics of Poly(ethylene glycol)-modified Polysaccharide MDG-1 from Ophiopogon Japonicus 1,2 2 1 1,2 2,3 1,2 1 Xiao Lin , Yan Jiang , Zhuojun Wang , Yi Feng , Desheng Xu , Lan Shen ( College of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 2 Shanghai 201203, China; Engineering Research Center of Modern Preparation Technology of 3 TCM of Ministry of Education, Shanghai 201203, China; Shuguang Hospital of Shanghai, Shanghai 200021, China) ABSTRACT :OBJECTIVE To improve the pharmacokinetics of polysaccharide MDG- 1 from Ophiopogon Japonicus by modifying MDG- 1 with polyethylene glyco l (PEG). METHODS Amino-methoxypoly(ethylene glycol) was used to modify MDG- 1 and the molecular weight and grafting degree of conjugates were determined by HPGPC. Pharmacokinetics of conjugates was assessed in rats. RESULTS Optimal modification conditions were obtained. Several conjugates having 1 molecular-weight-different PEG and different grafting degree were prepared. Biological half- lives of the conjugates were