文章摘要
徐明明,赵沁,周勤,郑璐侠,陈钢,邵泓.人血白蛋白中蛋白聚合物的研究[J].中国药事,2021,35(11):1246-1252
人血白蛋白中蛋白聚合物的研究
Research of Protein Aggregates in Human Albumin
  
DOI:10.16153/j.1002-7777.2021.11.007
中文关键词: 人血白蛋白  蛋白聚合物  亚可见颗粒  不溶性微粒  可见颗粒/可见异物
英文关键词: human albumin  protein aggregates  subvisible particulate matter  particulate matter  visible particulates
基金项目:
作者单位
徐明明 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
赵沁 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
周勤 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
郑璐侠 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
陈钢 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
邵泓 上海市食品药品检验研究院,国家食品药品监督管理局治疗类单抗质量控制重点实验室,上海 201203 
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中文摘要:
      目的:研究人血白蛋白中不同尺寸的蛋白聚合物的现状,探讨不同尺寸蛋白聚合物之间的相关性,改进检测方法,提升血液制品类生物制品质量。方法:采用分子排阻色谱法、微流成像颗粒分析技术、光阻法、人工灯检法分别对5家企业的人血白蛋白样品中纳米级可溶的聚合物、1~100 µm亚可见颗粒、≥10 µm和≥25 µm的不溶性微粒、≥50 µm的可见颗粒进行检测。结果:纳米级可溶的聚合物结果在不同企业间存在一定差异,企业D、企业E的含量低于其他3家企业。亚可见颗粒结果在不同企业间存在较大差异,其中企业C约是企业B数量的10倍。不溶性微粒和可见异物结果各企业间基本无差异。结论:4种不同的分析方法检测到的不同尺寸蛋白聚合物结果相互之间没有明显的相关性,且蛋白的单体、低聚物、亚微米颗粒、亚可见颗粒、可见颗粒聚合途径受多种因素影响,小分子蛋白聚合物的含量多少并不是大分子亚可见颗粒和可见颗粒形成的唯一前提。因此,监测和控制部分蛋白聚合物不能获取其他蛋白聚合物的信息。在质量标准中应联合采用多种方法,分别对不同尺寸的蛋白聚合物进行检测和限定,全面控制药品质量。
英文摘要:
      Objective: To study protein aggregates of different sizes in human albumin and discuss their correlation, so as to improve the detection methods and promote the quality of biological products of human blood. Methods: SEC-HPLC, light obscuration particle count test, Micro-flow imaging (MFI) and lamp test were used separately to study the nanometer soluble aggregates, 1~100µm subvisible particulate matter, ≥10µm and ≥25µm particulate matter, ≥50µm visible particulates in human albumin from five enterprises. Results: The results of nanometer soluble aggregates shows some differences among different enterprises, and the content of enterprise D and E are lower than that in other three enterprises. The results of subvisible particulate matter vary greatly among different enterprises, and the number of the subvisible particulate matter of enterprise C is about ten times of enterprise B. The result of particulate matter and visible particulates shows little difference among enterprises. Conclusion: There is no significant correlation between the results of different size protein aggregates with four different analysis methods. And the polymerization pathway of protein monomer, oligomer, submicroparticulate matter, subvisible particulate matter and visible particulate matter is affected by many factors. The content of small molecule polymer is not the only premise for the formation of large molecule particulate matter and visible particles. Therefore, monitoring and controlling some protein aggregates can not obtain information about others. In the quality standard, various methods should be combined to detect and limit protein aggregates of different sizes in specification in order to control the quality of drugs.
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