醛糖还原酶抑制剂治疗糖尿病周围神经病变的临床试验研究进展  

Progress in Clinical Trials of Aldose Reductase Inhibitors in the Treatment of Diabetic Peripheral Neuropathy

作　　者：周健[1] 方莲花[1] 吕扬[1] 杜冠华[1] ZHOU Jian;FANG Lianhua;LÜYang;DU Guanhua(Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Research for Cerebrovascular Diseases,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,脑血管病新药发现及晶型研究北京市重点实验室,北京100050

出　　处：《中国药学杂志》2025年第6期553-558,共6页Chinese Pharmaceutical Journal

基　　金：北京市自然科学基金项目资助(7232258)。

摘　　要：糖尿病周围神经病变是糖尿病最常见的并发症之一,醛糖还原酶是糖尿病周围神经病变等多种糖尿病并发症发病机制中的关键酶。笔者系统综述了5种醛糖还原酶抑制剂用于治疗糖尿病周围神经病变临床试验的有效性与安全性研究进展。依帕司他是至今唯一在临床应用的醛糖还原酶抑制剂,多项临床试验表明其对于糖尿病周围神经病变具有一定的治疗作用且具有足够的安全性,但是长期研究表明其治疗效果不优于甲钴胺。托瑞司他、唑泊司他、泊那司他及非达司他均由于有效性或安全性问题未能上市或被撤市,可能与药物的结构特征有关。从药物结构出发,研究和开发更为有效和安全的醛糖还原酶抑制剂治疗糖尿病周围神经病变将成为未来的研究重点之一。Diabetic peripheral neuropathy is one of the most common complications of diabetes.Aldose reductase is a key enzyme in the pathogenesis of diabetic complications.This review systematically reviews the efficacy and safety of five kinds of aldose reductase inhibitors in the treatment of diabetic peripheral nerves.Epalrestat is the only aldose reductase inhibitor in clinical application so far.A number of clinical trials have shown that epalrestat has a certain therapeutic effect on diabetic peripheral neuropathy and has sufficient safety,but long-term studies have shown that its therapeutic effect is not better than mecobalamine.Torrestat,zoporestat,ponastat,and fedastat were all withheld from the market or withdrawn from the market due to efficacy or safety concerns,which was inferred to be related to the structural characteristics of the drugs.Development of more effective and safer aldose reductase inhibitors from the perspective of drug structure will become one of the future research focuses on diabetic peripheral neuropathy.

关 键 词：醛糖还原酶抑制剂 糖尿病周围神经病变 临床试验 依帕司他 

分 类 号：R969[医药卫生—药理学]