生物类似药(YD057)与杜拉鲁肽关键质量属性比对研究  

Comparison Study on the Critical Quality Attributes between Similar Biological Medicine(YD057) and Dulaglutide

作　　者：代亚东 彭红卫 苟凡铖 侯怡铃[1] 丁祥[1] 

机构地区：[1]西华师范大学生命科学学院,西南野生动植物资源保护省部共建教育部重点实验室,四川南充637009

出　　处：《中国药学杂志》2018年第4期300-305,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(31400016,31200012)

摘　　要：目的通过基因重组表达的生物类似药GLP-1-Fc融合蛋白(YD057)与上市产品杜拉鲁肽进行关键质量属性比对研究,分析其有无显著差异。方法采用聚丙烯酰胺凝胶电泳(SDS-PAGE)、分子排阻色谱法(SEC)、毛细管电泳法(CE-SDS)、毛细管等电聚焦(CIEF)分析其理化性质在相对分子质量、纯度、电荷异质性是否存在差异,通过肽图分析其在氨基酸一级序列是否一致,通过寡糖分布测定N糖修饰比例是否一致,在体外生物学活性测定以及GLP-1受体结合力分析来评价细胞学功能与分子结合力方面是否一致。结果生物类似药(YD057)与杜拉鲁肽在理化性质、氨基酸一级序列、N糖修饰比例、细胞生物学功能与受体结合力都无显著差异。结论两者关键质量属性(CQA)基本一致。OBJECTIVE To investigate whether there is significant difference between the GLP-1-Fc fusion protein（ YD057 ） that is expressed by gene recombination and the marketed drug dulaglutide （Lilly）. METHODS SDS-PAGE, SEC, CE-SDS and ClEF were used to analyze the differences in molecular weight, purity and charge heterogeneity. The amino acid sequence, biological activity and receptor binding analysis were measured to assess whether the cytological function and molecular binding capacity were consistent. Oligosaccharide distribution was measured to assess whether N-linked glycosylation modification ratio was consistent. RESULTS There was no significant difference in physicochemical properties, amino acid primary sequence, N-linked glycosylation modification ratio, cell biology function and receptor binding capacity between the biological similar drugs（YD057） and dulaglutide. CONCLUSION Their critical quality attributes are basically the same.

关 键 词：生物类似药 杜拉鲁肽 关键质量属性 

分 类 号：R917[医药卫生—药物分析学]