麦冬多糖MDG-1聚乙二醇修饰物的合成与药动学研究

Synthesis and Pharmacokinetics of Poly(Ethylene Glycol)-Modified Polysaccharide MDG-1 from Ophiopogon japonicus

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表观相对分子质量与接枝率,并考察其药动学性质。结果确定了优化的合成条件,制得多种用不同相对分子质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相对分子质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。

OBJECTIVE To improve the pharmacokinetic properties of polysaccharide MDG-1 from Ophiopogon japonicus by modifying MDG-1 with polyethylene glycol（PEG）.METHODS Linear amino-terminated poly（ethylene glycol） methyl ether was used to modify MDG-1.The apparent molecular weight and grafting degree of conjugates were determined by high-performance gel permeation chromatography（HPGPC）.The pharmacokinetics of conjugates was investigated in rats.RESULTS Optimal modification conditions were obtained.Several conjugates with molecular-weight-different PEG and different grafting degree were prepared.The biological half-lives of the conjugates were significantly prolonged.And the prolongation was dependent not only on the molecular weight of PEG,but also on the grafting degree of the conjugates.CONCLUSION PEGylation is a promising method to improve pharmacokinetics of MDG-1.