主链含膦酸酯的聚酸酐药物控制释放材料研究

Studies on the Syntheses and Drug Release Properties of Polyanhydrides Containing Phosphonoformic(or Acetic)Acid Ethyl Ester in the Main Chain

通过二氯膦甲（乙）酸乙酯与对羟乙氧基苯甲酸反应，制备了二羧苯氧乙氧基膦甲（乙）酸乙酯，将其转化成混合醋酐并通过熔融缩聚，合成了主链含膦甲（乙）酸乙酯的聚酸酐.以二羧苯氧乙氧基膦甲（乙）酸乙酯，分别与1，3-双（4－羧基苯氧基）丙烷（CPP）及癸二酸（SA）共聚，得到相应的共聚酸酐.对所合成的单体和聚合物的结构进行了表征．研究了它们的体外降解、酶促降解及其对抗肿瘤药物5-氟尿嘧陡和氨甲蝶呤的释放性能．

Polyanhydrides were synthesized by melt polymerization of his (p--carboxyphenyloxy ethoxy), phosphonoformic (or acetic) acid ethyl ester 1(or 2). Copolyanhydrides weresimilarly prepared from 1 (or 2) and his(p--carboxyphenoxy)propane (CPP), or sebacic acid(SA). The chemical stru ctures of these new polyanhydrides and copolyanhydrides wereconfirmed by iH NMR, FTIR and elemental analysis. The average molecular weight of thesepolymers was investigated. In vitro degradation of polyanhydrides and copolyandhydrides inphosphate buffer solution at 37 'C was monitored by HPLC. Experimental data revealed thatfission of phosphate bond took place after that of the anhydride bond. Enzymatic degradationshowed that Ribonuclease could catalyze and accelerate the degr adation of thesepolyanhydrides. Drug release profile of antitumor agents MTX and 5--Fu were also studied.