MPEG-5-FU前药的合成与性能研究

Synthesis and Properties of Methoxypolyethylene Glycol-5-Fluorouracil Prodrugs

以不同分子量的聚乙二醇单甲醚(MPEG)钠盐与1-(氯代乙酰)-5-氟尿嘧啶反应,通过威廉森反应合成了聚乙二醇单甲醚-5-氟尿嘧啶(MPEG-5-FU)前药,采用红外光谱,核磁氢谱,紫外光谱进行了表征,证明5-氟尿嘧啶单元已经成功接载到聚乙二醇链的末端;随着MPEG分子量的提高,前药的水溶性增强。水解实验结果表明MPEG-5-FU前药具有长效缓释的功能,可以在不同pH值的缓冲液中释放出5-FU,当MPEG的分子量达到2 000时,前药的水溶性和释药速率最大。

A series of novel methoxypolyethylene glycol-5-Fluorouracil prodrugs were synthesized by Williamson reaction of sodium methoxypolyethylene glycol and 1-(chloroacetyl)-5-Fluorouracil.The MPEG-5-FU prodrugs were characterized by IR,1H-NMR and UV spectroscopy.The result showed that 5-FU was successfully connected to the ends of MPEG.As the molecular weight of MPEG increased,the water solubility of prodrugs improved.The hydrolysis measurement showed that the prodrugs had the function of longer duration of activity,due to slow release.The prodrugs obtained could release 5-FU in different pH buffer solution.When the molecular weight of MPEG reached 2000,the prodrug had the best water solubility and the highest drug release rate.