氮唑类抗真菌药物多晶型与共晶研究进展  

Research Progresses on Polymorphs and Cocrystals of Azole Antifungal Drugs

作　　者：邢文慧 喻红梅 房政钰 龚宁波[1] 吕扬[1] XING Wenhui;YU Hongmei;FANG Zhengyu;GONG Ningbo;LYU Yang(Beijing Key Laboratory of Polymorphs Drugs Research,Institute of Materia Medical,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China)

机构地区：[1]北京协和医学院、中国医学科学院药物研究所晶型药物研究北京市重点实验室,北京100050

出　　处：《医药导报》2022年第5期649-655,共7页Herald of Medicine

基　　金：国家重点研发计划(2016YFC1000900);中国医学科学院医学与健康科技创新工程项目(2017-12M-1-010);天然/有效活性小分子高效获取鉴定的技术集成体系构建及应用(2018ZX09711001-001);国家科技重大专项-重大新药创制(2017ZX09101001003,2018ZX09711001-001-013,2018ZX09711001-010)。

摘　　要：药物的固体存在形式包括多晶型、共晶和盐等多种形式。晶型的变化可以改变固体化学物质的多种理化性质,进而影响药物的临床疗效和安全性。药物共晶(盐)能够在不改变药物结构的情况下修饰药物分子,从而改善溶解度、增加稳定性、提高生物利用度等。共晶和盐的主要区别在于是否存在质子转移。多晶型和共晶(盐型)研究已成为药物设计、审批、生产和质量控制中不可缺少的重要环节。氮唑类药物通过改变膜的通透性对曲霉菌、白念珠菌等多种真菌具有抑制作用,是临床上极具应用前景的抗真菌药物。该文从氮唑类抗真菌药物(包括咪唑类、三唑类、第2代三唑类)出发,综述了酮康唑、伊曲康唑、伏立康唑等氮唑类药物的多晶型和共晶的国内外研究进展,为后续新型氮唑类药物的开发和利用提供参考和借鉴。The solid forms of drugs include polymorphs,cocrystals,and salts.The change of crystal form can change a variety of physical and chemical properties of solid chemical substances,thereby affecting the clinical efficacy and safety of the drug.Drug cocrystals(salts)can modify drug molecules without changing the structure of the drug,thereby improving solubility,increasing stability,improving bioavailability,etc.The main difference between cocrystal and salt is whether there is proton transfer.The research of polymorphs and cocrystals(salts)has become an indispensable and important link in drug design,approval,production,and quality control.Azazole drugs can inhibit various fungi such as Aspergillus and Candida albicans by changing the permeability of the membrane,and are antifungal drugs with great clinical application prospects.This paper,starting from azole antifungal drugs(including imidazoles,triazoles,and second-generation triazoles),reviews the domestic and foreign research progress of polymorphs and cocrystals of azole drugs such as ketoconazole,itraconazole,and voriconazole.We hope to provide reference for the subsequent development and utilization of new azole drugs.

关 键 词：氮唑 抗真菌 多晶型 共晶 

分 类 号：R978.5[医药卫生—药品] R944[医药卫生—药学]