强的松龙·葡聚糖连接物在大鼠胃肠道内容物中的水解

Prednisolone-dextran conjugate hydrolysis in rat gastrointestinal tract contents

目的 观察强的松龙·葡聚糖 (平均 Mr5 0万 )连接物的结肠定向释放特性 .方法 通过将所合成的强的松龙·葡聚糖连接物与大鼠胃肠道不同部位内容物稀释液一起孵育 ,观察强的松龙的释放情况 .结果 在 1 6 0 min的孵育过程中 ,强的松龙·葡聚糖连接物在胃肠道上部内容物中水解释放出少量强的松龙及强的松龙琥珀酸半酯 ,最大释放量小于3μm ol·L- 1 ;而在胃肠道下部内容物中水解释放出大量强的松龙及强的松龙琥珀酸半酯 ,最大释放量为 1 4μmol· L- 1 .结论 葡聚糖可保护其与强的松龙相连接的酯键免受胃肠道上部酯酶的水解 ,使强的松龙集中在结肠释放 .强的松龙·葡聚糖连接物可为一种能在结肠定向转释的药物 .

AIM To observe whether prednisolone·dextran (average K relative molecular mass 50×10 4) conjugate has potential in colon specific delivery of prednisolone. METHODS Prednisolone·dextran conjugate was incubated in rat contents of different part of gastrointestinal (GI) tract at 37℃, and the release of prednisolone was detected. RESULTS In 160 minutes incubation with 10 fold dilution of gastrointestinal tract contents, the concentration of drug released as prednisolone and prednisolonehemisuccinate in up per gastrointestinal tract was less than 3 μmol·L -1 ; whereas the concentration of drug released as prednisolone and prednisolonehemisuccinate in large intestine was 14 μmol·L -1 . CONCLUSION Dextran backbone protects drug polymer ester bound from hydrolysis by small intestinal esterases, and prednisolone·dextran conjugate has potential in colon specific delivery of prednisolone.