含磷聚酸酐药物控制释放材料的研究

Studies on the Syntheses and Properties of Phosphorus containing Polyanhydrides for DDS

将二氯磷酸乙酯或苯酯与对羟乙氧基苯甲酸反应，制备了含磷酸酯键的二羧酸．将其转化为混合酸酐并通过熔融缩聚，合成了主链含磷酸酯键的聚酸酐．以含磷酸酯键二羧酸与1，3－双（4－羧基苯氧基）丙烷（CPP）熔融共聚，得到主链含磷酸酯键的共聚酸酐．研究了两类聚酸酐的体外降解、酶促降解．这些聚酸酐的降解过程既包含酸酐键的断裂，也包含磷酸酯键断裂，前者比后者更容易断裂．核糖核酸酶和碱性磷酸酶能加速这类聚酸酐的降解．还研究了这些聚酸酐对广谱抗菌素环丙沙星的释放性能．

Phosphorus-containing polyanhydrides (2a, 2b ) and copolyanhydrides (la-CPP,1b-CPP) were synthesized by melt polycondensation using monomers bis (p-carboxypheny-loxyethyl ), ethyl phosphate and bis (p-carboxyphenyloxyethyl), phenyl phosphate. Their chemical structures were confirmed by 1H NMR, FTIR, UV and elementary analysis. The average molecular weight and store stability as well as thermostability of these polyanhydries and copolyanhydrides were investigated. The degradation of polyanhydrides in vitro in phosphate buffer solution at 37℃ was monitored by HPLC. The experimental data revealed that fission of phosphate bond took place after that of the anhydride bond. Enzymatic degradation showed that ribonuclease and alkaline phosphatase can catalyze and accelerate the degradation of these phosphorus-cotaning polyanhydrides. Drug release profile of ciprofloxacin was also studied.