5-氨基水杨酸甘氨酸盐在胃肠道内的稳定性研究

Study on the stability of 5-Aminosalicylyl-Glycine in the gastrointestinal tract

目的 研究5-氨基水杨酸甘氨酸盐(5-ASA-Gly)在大鼠胃肠道中的稳定性。方法 以SD大鼠为实验动物,采用高效液相色谱法考察了5-ASA-Gly在体内外胃、小肠环境下及大鼠盲肠内容物中5-氨基水杨酸(5-ASA)的分布情况。结果 5-ASA-Gly在胃和小肠环境下相当稳定,未释放出5-ASA;而在与人体结肠部位细菌环境非常类似的大鼠盲肠内容物中则有5-ASA出现。结论 5-ASA-Gly经盲结肠相关菌丛或酶丛的作用释放出游离药物5-ASA,大大降低了5-ASA的全身吸收,可作为一种有希望的结肠定位释药特定性前体药物加以研究与开发。

Purpose To study the stability of 5-Aminosalicylyl-Glycine in gastrointestinal tract. Methods Distribution of 5-Aminosalicylic acid(5-ASA)in lumina contents of GI tract was measured by HPLC after some experiments were performed in vitro and in vivo with SD rats. Results Stability of 5-ASA-Gly by peptidases was investigated by incubation of the drug with the contents of stomach or small intestine at 37℃. 5-ASA was not detected, indicating that the prodrug was stable in the upper intestine. The amount of 5-ASA liberated from incubation of the prodrug in cecal or colonic contents of rats was higher, which indicated that the prodrug activation took place more readily in the rat cecum whose bacterial counts are high like human colon. Conclusion Results from the experiments suggested that 5-ASA-Gly can obviate drug in upper GI tract and can be as a promising candidate of colon-specific prodrug of 5-ASA.