聚乙二醇化重组人尿酸氧化酶质控难点研究进展

Progress in Study on Difficulties of Quality Control of PEGylated UOX

聚乙二醇化重组人尿酸氧化酶(PEG-UOX)是对重组人尿酸氧化酶(UOX)进行聚乙二醇修饰以降低其免疫原性和延长体内半衰期为目的的改构药物。由于它是聚乙二醇随机多位点修饰的蛋白药物,使得修饰后的蛋白质在理化性质以及体内外活性上的复杂程度都远远超出重组人尿酸氧化酶。对于此类药物,目前国内外无标准化的质量分析方法。笔者通过整理、归纳近年来关于聚乙二醇修饰药物质控分析技术的文献,对聚乙二醇化重组人尿酸氧化酶的3个关键质量控制难点——聚乙二醇对重组人尿酸氧化酶的平均修饰率、修饰均一度以及聚乙二醇在重组人尿酸氧化酶上的修饰位点所涉及的分析手段进行了综述,以期对国内企业开发此药物提供技术指导。

PEGylated UOX is a kind of modified pharmaceuticals designed by coupling PEG with UOX to increase in vivo circulation half-life and reduce immunogenicity. UOX is modified by PEG at random multiple sites, which RESULTS in more complicated physical and chemical characteristics and in vivo and in vitro activities than UOX. At present, there is no standardized quality analysis method for such drugs. Through collecting and summarizing references about the quality control method of PEG-modified drugs in recent years, this article summarizes the analysis METHODS for three difficulties of the quality control of UOX namely the average extent of modification, consistency of modification and PEGylation sites so as to provide technical guidance for enterprises to develop the drug.