Okagawa T, Fujita T, Murakami M, Yamamoto A, Shimura T, Tabata S, Kondo S, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Life Sci. 1994;55(9):677-83. doi: 10.1016/0024-3205(94)00674-1.
In order to estimate the intestinal stability of ebiratide [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], a novel adrenocorticotropic hormone (ACTH) analogue, after oral administration, the hydrolytic properties of ebiratide were determined in the rat small intestinal fluid and mucosal homogenates. Ebiratide was extremely stable in the rat small intestinal fluid, while it was degraded in various intestinal mucosal homogenates. Regional differences were observed in its proteolytic properties; e.g., the hydrolytic rates of ebiratide in jejunal and ileal mucosal homogenates were 2-3 times faster than that in duodenal and colonic homogenates. Degradation of ebiratide was markedly inhibited by aminoprotease inhibitors such as sodium glycocholate, puromycin, bestatin and bacitracin. These results suggest that co-administration of certain protease inhibitors are useful to improve the stability of ebiratide in the intestine.
为了评估新型促肾上腺皮质激素（ACTH）类似物依比拉肽[H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2]口服给药后的肠道稳定性，在大鼠小肠液和黏膜匀浆中测定了依比拉肽的水解特性。依比拉肽在大鼠小肠液中极其稳定，而在各种肠道黏膜匀浆中会降解。观察到其蛋白水解特性存在区域差异；例如，依比拉肽在空肠和回肠黏膜匀浆中的水解速率比在十二指肠和结肠匀浆中快2至3倍。氨基蛋白酶抑制剂如甘氨胆酸钠、嘌呤霉素、贝司他汀和杆菌肽可显著抑制依比拉肽的降解。这些结果表明，联合使用某些蛋白酶抑制剂有助于提高依比拉肽在肠道中的稳定性。
