我国近年人血源FⅧ制品主要功能成分的变化及分析*

doi:10.3969/j.issn.1671-2587.2025.03.013

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (3): 360-367.DOI: 10.3969/j.issn.1671-2587.2025.03.013

我国近年人血源FⅧ制品主要功能成分的变化及分析^*

赵韩¹, 裴仁俊^1,2, 王彩贤¹, 杜晞¹, 黎小月¹, 蒋鹏¹, 林方昭¹, 孙盼¹, 曹海军¹

¹中国医学科学院北京协和医学院输血研究所, 四川成都 610025;
²浙江大学医学院附属邵逸夫医院, 浙江杭州 310016

收稿日期:2024-12-23 发布日期:2025-06-23
通讯作者: 曹海军,主要从事输血医学研究,（E-mail）chjr007@163.com。共同通信作者孙盼,主要从事输血医学研究,（E-mail）sunpan_1@163.com。
作者简介:赵韩,主要从事输血医学及公共卫生研究,（E-mail）unicornzh2002@163.com。
基金资助:
*本课题受国家药品监督管理局血液制品质量控制重点实验室（依托单位：广东省药品检验所）开放课题（No.KF2021008）、中国输血协会威高科研基金项目（No.CSBT-WG-2021-02）、中国医学科学院医学与健康科技创新工程重大协同创新项目（No.2021-I2M-1-060）资助

Changes of Main Functional Components of Human Plasma-derived Factor Ⅷ Products in China in Recent Years

ZHAO Han¹, PEI Renjun^1,2, WANG Caixian¹, DU Xi¹, LI Xiaoyue¹, JIANG Peng¹, LIN Fangzhao¹, SUN Pan¹, CAO Haijun¹

¹Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052;
²Sir Run Run Shaw Hospital Affiliated with the Zhejiang University School of Medicine

Received:2024-12-23 Published:2025-06-23

摘要/Abstract

摘要： 目的分析我国近年人血源FⅧ制品主要功能成分的变化,为我国血浆蛋白制品的研发、人血源FⅧ制品制备工艺的改进及临床应用提供参考。方法将我国目前市售的9家公司生产的人血源FⅧ制品（A-I）按说明书要求溶解,采用BCA法检测蛋白浓度、一期法检测FⅧ活性、免疫比浊法检测VWF活性和VWF抗原含量,计算出FⅧ比活、VWF:Ac/FⅧ：C和VWF:Ac/VWF:Ag,并与2015—2017年生产的制品（a-g）进行对比,分析我国近年人血源FⅧ制品主要功能成分的变化。结果制品A-I中FⅧ活性均值为（20.70±2.06） IU/mL,与以往制品相比无显著差异;比活均值为（36.53±19.20） IU/mg,较以往显著提升（P<0.01）;VWF:Ac/FⅧ：C可反映制品中VWF活性占比,均值为0.43±0.12,与以往制品相比显著下降（P<0.000 1）;VWF:Ac/VWF:Ag可反映VWF的完整性和多聚体组成,均值为0.70±0.16,较以往明显下降（P<0.01）。与国外制品Wliate^®相比, 目前我国制品中FⅧ比活（P<0.05）与VWF活性（P<0.000 1）均明显低于Wliate^®。结论目前我国生产的人血源FⅧ制品纯度远高于《中国药典》（2020年版）的要求,且较以往显著提升,但药典要求外的VWF的质量活性下降,均不适宜于治疗VWD。此外,与国外制品相比,我国人血源FⅧ制品在FⅧ纯度和VWF活性上有较大的提升空间。

关键词: 人凝血因子Ⅷ制品, 血管性血友病因子, 血管性血友病, 人凝血因子Ⅷ, 甲型血友病

Abstract: Objective The changes in the main functional components of human plasma-derived factor Ⅷ (FⅧ)products in China in recent years were analyzed to provide a reference for the development of plasma protein products, improvement of the preparation processes of plasma-derived FⅧ, and their clinical application. Methods Nine commercially available FⅧ products (A-I) from Chinese manufacturers were dissolved according to the instructions. Protein concentration was measured using the BCA method, FⅧ activity was determined by a one-stage method, VWF activity and VWF antigen were assessed by immunoturbidimetry. The specific activity of FⅧ, the ratio of VWF:Ac/FⅧ:C and VWF:Ac/VWF:Ag were calculated and compared with products produced between 2015 and 2017 (a-g). The changes of main functional components of FⅧ were analyzed. Results The average FⅧ activity of product A-I was (20.70±2.06) IU/mL, showing no significant difference compared to previous products. The mean specific activity was (36.53±19.20) IU/mg, significantly higher than before (P<0.01). The average VWF:Ac/FⅧ:C was 0.43±0.12, indicating a significant decrease compared to previous products (P<0.000 1). The mean VWF:Ac/VWF:Ag was 0.70±0.16, also significantly lower than before (P<0.01). Compared with foreign product Wilate®, Chinese products exhibited significantly lower FⅧ specific activity (P<0.05) and VWF activity (P<0.000 1). Conclusion Currently, the purity of human plasma-derived FⅧ products in China exceeds the requirements of the Chinese Pharmacopoeia (2020 edition), and has significantly improved compared to the past. However, the quality of VWF activity has decreased making these products less suitable for treating von Willebrand disease (VWD). Compared with foreign products, human plasma-derived FⅧ products in China have a greater improvement in both FⅧ purity and VWF activity.

Key words: Human coagulation factor Ⅷ concentrates products, Von Willebrand factor, Von Willebrand disease, Human coagulation factor Ⅷ, Hemophilia A

中图分类号:

R977.8R331.1

赵韩, 裴仁俊, 王彩贤, 杜晞, 黎小月, 蒋鹏, 林方昭, 孙盼, 曹海军. 我国近年人血源FⅧ制品主要功能成分的变化及分析^*[J]. 临床输血与检验, 2025, 27(3): 360-367.

ZHAO Han, PEI Renjun, WANG Caixian, DU Xi, LI Xiaoyue, JIANG Peng, LIN Fangzhao, SUN Pan, CAO Haijun. Changes of Main Functional Components of Human Plasma-derived Factor Ⅷ Products in China in Recent Years[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(3): 360-367.

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我国近年人血源FⅧ制品主要功能成分的变化及分析^*

Changes of Main Functional Components of Human Plasma-derived Factor Ⅷ Products in China in Recent Years

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