5-氨基水杨酸和丁酸盐的结肠靶向互用前药治疗溃疡性结肠炎,RSC Advances

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5-氨基水杨酸和丁酸盐的结肠靶向互用前药治疗溃疡性结肠炎
RSC Advances ( IF 3.9 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1039/c7ra13011b
Yan Yan ₁ , Jinyao Sun ₂ , Xianting Xie ₂ , Pengchong Wang ₁ , Ying Sun ₁ , Yalin Dong ₂ , Jianfeng Xing ₁

Affiliation

本研究的目的是设计和合成 5-氨基水杨酸 (5-ASA) 和丁酸盐的四种结肠靶向互用前药，并评估它们对溃疡性结肠炎的治疗效果。在此，制备并表征了5-ASB、5-ASDB、Ols-DB和Ols-DBP，并研究了它们的亲油性、溶解性、体外和体内稳定性。最后，通过以下方法评估前药对实验性结肠炎的改善作用一系列指标，包括小鼠体重和存活率、结肠指数和结肠损伤评分、疾病活动指数、髓过氧化物酶活性和结肠组织中超氧化物歧化酶、丙二醛、谷胱甘肽和谷胱甘肽过氧化物酶的水平。结果，5-ASB 非常稳定，但 Ols-DB 在胃肠道环境中表现出极端的不稳定性，而 5-ASDB 和 Ols-DBP 表现出理想的结肠靶向特性。四种前药对实验性结肠炎均有一定的治疗作用。当对小鼠口服给药时，5-ASDB 和 Ols-DBP 的效果明显大于 5-ASA 和丁酸钠的混合物。Ols-DB 被用作灌肠剂，其效果与 5-ASDB 和 Ols-DBP 一样。此外，

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Colon-targeting mutual prodrugs of 5-aminosalicylic acid and butyrate for the treatment of ulcerative colitis

The aim of this study was to design and synthesize four colon-targeting mutual prodrugs of 5-aminosalicylic acid (5-ASA) and butyrate, and evaluate their therapeutic effects on ulcerative colitis. Herein, 5-ASB, 5-ASDB, Ols-DB and Ols-DBP were prepared and characterized, and their lipophilicity, solubility, in vitro and in vivo stability were investigated. Finally, the ameliorative effects of the prodrugs on experimental colitis were evaluated via a series of indicators, including the body weight and survival rates of mice, the colon index and colonic damage score, the disease activity index, the myeloperoxidase activity and levels of superoxide dismutase, malondialdehyde, glutathione and glutathione peroxidase in colonic tissues. As a result, 5-ASB was very stable but Ols-DB showed extreme instability in the environment of the gastrointestinal tract, while 5-ASDB and Ols-DBP showed desirable colon-targeting properties. The four prodrugs all had certain therapeutic effects on the experimental colitis. When orally administered to mice, 5-ASDB and Ols-DBP had significantly greater effects than the mixture of 5-ASA and sodium butyrate. Ols-DB was used as an enema and could be as effective as 5-ASDB and Ols-DBP. In addition, the therapeutic effects of the synthesized prodrugs might be associated with their anti-oxidative damage ability.

更新日期：2018-01-11

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