单硝酸异山梨酯孪药合成及其性能研究

 目的设计并合成单硝酸异山梨酯与阿司匹林组成的孪药,评价该类前药的药理作用和生物活性。方法对单硝酸异山梨酯孪药进行了IR、MS、NMR结构确证,测定了脂水分配系数、血浆酶催化水解速率、体外药理活性、胃肠道刺激性。结果单硝酸异山梨酯孪药(Prodrug 1,Prodrug 2)的logP值分别为0.89、0.45,在血浆中水解t_1/2(2～4min);对二磷酸腺苷(ADP)诱导血小板聚集抑制率为50.9%～52.4%。结论单硝酸异山梨酯组合前药在血浆迅速水解为原药及相关产物,与阿司匹林比较抗血小板活性相近,胃肠道刺激性明显减小。

Synthesis and Evaluation of Twin Drugs of Isosorbide Mononitrate and Aspirin

OBJECTIVE To design and synthesize twin drugs of isosorbide mononitrate and aspirin and to evaluate their pharmacological character,hydrolysis and anti-platelet effects.METHODS Both compounds were identified by elementary analysis.IR,MS and NMR.The hydrolysis and anti-platelet effects of both compounds were studied in buffer solution and 10% buffered rabbit plasma.RESULTS Both compounds are hydrolysed rapidly t_1/2 2～4 min.The rate of platelet aggregation inhibition was in the range of 50.9%～52.4%.CONCLUSION Both compounds had good anti-platelet effect,for gastrointestinal irritation was reduced significantly.