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用于评估受试物质/产品缓泻活性的临床前实验模型:文献综述

Preclinical experimental models for assessing laxative activities of substances/products under investigation: a scoping review of the literature.

作者信息

Kongdang Patiwat, Pruksakorn Dumnoensun, Koonrungsesomboon Nut

机构信息

Musculoskeletal Science and Translational Research (MSTR) Center, Faculty of Medicine, Chiang Mai University Chiang Mai, Thailand.

Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University Chiang Mai, Thailand.

出版信息

Am J Transl Res. 2022 Feb 15;14(2):698-717. eCollection 2022.

Abstract

Constipation is a common gastrointestinal problem worldwide. Its impact on health can range from an unpleasant problem to being seriously troublesome. When lifestyle modification fails to deal with constipation, laxatives are the mainstay of therapy. There are several types of laxatives currently available; however, there still remains a need for better laxatives because certain currently available laxatives are not appropriate for or accessible to some patients. Preclinical experiments to study the laxative potential of substances/products of interest are vital to improving that situation. The selection of appropriate experimental models for assessing the laxative activities of substances/products under investigation is crucial to achieving valid and meaningful results. This article provides a scoping review of the literature, outlining, and summarizing models currently being used in preclinical experiments assessing the laxative activities of substances/products under investigation. The review includes both screening models, e.g., the isolated organ bath system, fecal assessment and intestinal transit assay, and confirmation models, e.g., constipation models. Chemical substances/drugs used to induce constipation in constipation models, e.g., loperamide, diphenoxylate, montmorillonite, and clonidine, as well as standard laxative agents used as a positive control in experimental models, e.g., bisacodyl, carbachol, lactulose, sodium picosulfate, castor oil, phenolphthalein, and yohimbine, are described in detail. The purpose of this article is to assist researchers in the design and implementation of preclinical experimental models for assessing laxative activities of substances/products under investigation to achieve valid and meaningful preclinical results prior to experimentation in humans.

摘要

便秘是全球常见的胃肠道问题。其对健康的影响范围从一个令人不适的问题到严重困扰不等。当生活方式调整无法解决便秘问题时,泻药是主要的治疗手段。目前有几种类型的泻药;然而,仍然需要更好的泻药,因为某些现有的泻药对一些患者不合适或无法获得。研究感兴趣的物质/产品的缓泻潜力的临床前实验对于改善这种情况至关重要。选择合适的实验模型来评估所研究物质/产品的缓泻活性对于获得有效且有意义的结果至关重要。本文对文献进行了范围综述,概述并总结了目前在评估所研究物质/产品缓泻活性的临床前实验中使用的模型。该综述包括筛选模型,如离体器官浴系统、粪便评估和肠道转运试验,以及确认模型,如便秘模型。详细描述了用于在便秘模型中诱导便秘的化学物质/药物,如洛哌丁胺、地芬诺酯、蒙脱石和可乐定,以及在实验模型中用作阳性对照的标准泻药,如比沙可啶、卡巴胆碱、乳果糖、匹可硫酸钠、蓖麻油、酚酞和育亨宾。本文的目的是帮助研究人员设计和实施用于评估所研究物质/产品缓泻活性的临床前实验模型,以便在人体实验之前获得有效且有意义的临床前结果。

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