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脲酶抑制剂的发展:在儿童幽门螺杆菌感染的更好治疗方面存在哪些机遇?

The Development of Urease Inhibitors: What Opportunities Exist for Better Treatment of Helicobacter pylori Infection in Children?

作者信息

Hassan Sherif T S, Šudomová Miroslava

机构信息

Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 61242 Brno, Czech Republic.

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6-Suchdol, Czech Republic.

出版信息

Children (Basel). 2017 Jan 4;4(1):2. doi: 10.3390/children4010002.

Abstract

Stomach infection with ( causes severe gastroduodenal diseases in a large number of patients worldwide. The infection breaks up in early childhood, persists lifelong if not treated, and is associated with chronic gastritis and an increased risk of peptic ulcers and gastric cancer. In recent years, the problem of drug-resistant strains has become a global concern that makes the treatment more complicated and the infection persistent at higher levels when the antibiotic treatment is stopped. Such problems have led to the development of new strategies to eradicate an infection. Currently, one of the most important strategies for the treatment of infection is the use of urease inhibitors. Despite the fact that large numbers of molecules have been shown to exert potent inhibitory activity against urease, most of them were prevented from being used in vivo and in clinical trials due to their hydrolytic instability, toxicity, and appearance of undesirable side effects. Therefore, it is crucial to focus attention on the available opportunities for the development of urease inhibitors with suitable pharmacokinetics, high hydrolytic stability, and free toxicological profiles. In this commentary, we aim to afford an outline on the current status of the use of urease inhibitors in the treatment of an infection, and to discuss the possibility of their development as effective drugs in clinical trials.

摘要

幽门螺杆菌(Helicobacter pylori,Hp)感染在全球大量患者中引发严重的胃十二指肠疾病。幽门螺杆菌感染在儿童早期开始,若不治疗会终身持续,并与慢性胃炎以及消化性溃疡和胃癌风险增加相关。近年来,耐药菌株问题已成为全球关注的焦点,这使得治疗更加复杂,且在停止抗生素治疗后感染持续处于较高水平。此类问题促使人们开发根除幽门螺杆菌感染的新策略。目前,治疗幽门螺杆菌感染最重要的策略之一是使用脲酶抑制剂。尽管大量分子已显示出对幽门螺杆菌脲酶具有强大的抑制活性,但由于其水解不稳定性、毒性以及出现不良副作用,大多数分子无法用于体内和临床试验。因此,关注开发具有合适药代动力学、高水解稳定性和无毒性特征的脲酶抑制剂的现有机会至关重要。在本评论中,我们旨在概述脲酶抑制剂在治疗幽门螺杆菌感染方面的当前使用状况,并讨论其在临床试验中作为有效药物开发的可能性。

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