摘要
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t1/2(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。
Abstract
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 t1/2 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.
关键词
阿斯匹林 /
单硝酸异山梨酯 /
孪药 /
抑制血小板聚集
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Key words
aspirin /
isosrbide mononitrate(ISMN) /
twin drugs /
platelet inhibition
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徐春丽;吴燕燕;汪静;陈永顺;阮启蒙;束家有.
单硝酸异山梨酯孪药合成及其性能研究[J]. 中国药学杂志, 2009, 44(08): 634-636
XU Chun-li;WU Yn-yn;WNG Jing;CHEN Yong-shun;RUN Qi-meng;SHU Ji-you.
Synthesis and Evaluation of Twin Drugs of Isosorbide Mononitrate and Aspirin [J]. Chinese Pharmaceutical Journal, 2009, 44(08): 634-636
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参考文献
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脚注
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