降糖多肽药物固相合成有关物质研究综述

Review on the Related Substances of Synthetic Peptides Drugs in Solid Phase

近年来糖尿病患病人数日益增多,鉴于此,糖尿病类药物发展很快,尤其以多肽类药物发展最快,但大多数多肽药物在体内半衰期短,生物利用度低,因此寻找长效的降糖药物势在必行。目前多肽药物主要通过动植物中提取、化学合成和基因重组三种方式来制备,多肽药物化学合成方法是主要制备工艺之一,但化学合成过程中产生的有关物质会对产品质量有一定的影响。目前多肽药物主要采用固相多肽合成技术,该方法反应容器单一,容易实现自动化,但是该过程容易产生有关物质,并且多肽药物在合成、储存过程中,容易形成相关结构杂质,例如氨基酸丢失、氨基酸插入、保护基残留、氧化/还原等。本文主要介绍多肽药物有关物质,重点从固相合成工艺杂质方面展开综述,调研了国内外目前的研究现状,以期能探索出多肽药物其他的开发关键点,为这类药物的产业开发奠定基础。

In recent years,the number of patients with diabetes is increasing day by day.In view of this,diabetes drugs have developed rapidly,especially polypeptide drugs,but most polypeptide drugs have short half-life in vivo and low bioavailability,so it is imperative to find long-term hypoglycemic drugs.At present,polypeptide drugs are mainly prepared by extraction from animals and plants,chemical synthesis and gene recombination.Chemical synthesis of polypeptide drugs is one of the main preparation processes,but the related substances produced in the process of chemical synthesis will have a certain impact on product quality.At present,solid-phase polypeptide synthesis technology is mainly used for polypeptide drugs,which has a single reaction vessel and is easy to realize automation,but the process is easy to produce related substances,and related structural impurities,such as amino acid loss,amino acid insertion,protective group residue,oxidation/reduction,etc.,are easy to form during the synthesis and storage of polypeptide drugs.This paper mainly introduces the related substances of polypeptide drugs,focusing on the impurities in solid-state synthesis process,and investigates the current research status at home and abroad,in order to explore other key points in the development of polypeptide drugs and lay a foundation for the industrial development of such drugs.