含5-氟尿嘧啶的氨基甲酸聚乙二醇酯前药的合成与表征

采用异氰酸-α-氯乙酰酯与不同相对分子质量的聚乙二醇反应得到双氯乙酰氨基甲酸聚乙二醇酯,由于端基的α-氯具有良好的反应活性,将它与抗肿瘤药物5-氟尿嘧啶结合制备不同相对分子质量的高分子前药。对产物进行红外、核磁、紫外表征,证明5-氟尿嘧啶已经成功接到聚乙二醇链的末端,由紫外分光光度法测得最大载药量为22.6%。与5-氟尿嘧啶相比,前药的水溶性得到增强,而且具有长效缓释的功能。前药在不同pH的缓冲液中可以释放5-氟尿嘧啶或其衍生物,当聚乙二醇相对分子质量为2000时水解速度最快,20h的最大释药率为71.5%。

Synthesis and characterization of polyethylene glycol urethane prodrugs containing 5-fluorouracil

A series of polyethylene glycol derivates was synthesized by the reaction of α-chloroacetyl isocyanate with polyethylene glycol.Owing to the good reactive activity of α-chlorin in terminal,it can react with 5-fluorouracil,and the prodrug could be obtained.The prodrug was characterized by FTIR,1HNMR and UV spectroscopy and confirmed that the 5-fluorouracil unit was successfully connected to polyethylene glycol terminal.The maxmium loading content of prodrug was 22.6% measured by UV and it showed enhanced water solubility and longer duration of activity due to slow release compared with 5-fluorouracil.The prodrugs could release 5-fluorouracil or its derivatives in different pH solutions.When the molecular weight reaches 2 000,it has the fastest hydrolyzation speed.The maximum drug release percentage was 71.5% in 20 h.