中国药物警戒 ›› 2026, Vol. 23 ›› Issue (8): 848-851.
DOI: 10.19803/j.1672-8629.20250932

• 基础与临床研究 • 上一篇    下一篇

长效促红细胞生成素体内生物学活性检测方法研究

刘学1, 王巧旭1,Δ, 王涵1, 齐莉莉1, 航艾1, 张静娴2, 冯震1,*   

  1. 1上海市药品检验研究院药理毒理研究所,上海 201203;
    2国家药品监督管理局监管科学创新研究基地,上海市药品检验研究院中药天然药物研究所,上海 201203
  • 收稿日期:2025-12-24 出版日期:2026-08-15 发布日期:2026-08-17
  • 通讯作者: *冯震,男,博士,副主任技师,药检药理。E-mail: fengzhen@yjj.shanghai.gov.cn
  • 作者简介:刘学,男,硕士,药师,药检药理。Δ为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（81903800）; 上海市市场监督管理局科技项目（2025KJ74）; 上海市科学技术委员会科研计划（19DZ2202600）; 国家重点研发计划（2017YFC1702004）

An in vivo biological activity detection method for long-acting erythropoietin

Liu Xue1, Wang Qiaoxu1,Δ, Wang Han1, Qi Lili1, Hang Ai1, Zhang Jingxian2, Feng Zhen1,*   

  1. 1Division of Pharmacology and Toxicology, Shanghai Institute for Drug Control, Shanghai 201203, China;
    2NMPA Center for Innovation and Research in Regulatory Science, Division of Traditional Chinese Medicines and Natural Medicines, Shanghai Institute for Drug Control, Shanghai 201203, China
  • Received:2025-12-24 Online:2026-08-15 Published:2026-08-17

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摘要： 目的 研究长效促红细胞生成素（Erythropoietin, EPO）在小鼠体内的药效学特征,探索建立适用于长效EPO的体内生物学活性检测方法。方法 依据《中华人民共和国药典》中EPO生物学活性测定法（网织红细胞法）,给予小鼠皮下注射不同剂量的长效或短效EPO,连续考察给药后d 1~d 10小鼠血液中网织红细胞百分比的变化趋势,设计科学合理的给药剂量和取血检测时间,建立长效EPO体内生物学活性测定方法,并开展长效EPO的生物学活性检查。结果 按照量反应平行线3.3法生物统计模型,小鼠给予低、中、高剂量的长效EPO分别0.2、0.4、0.8 IU•只-1时,3批长效EPO的体内生物学活性分别为94%（FL% 23%）、94%（FL% 17%）和92%（FL% 15%）;d 4为最佳采血时间,采血时间与短效EPO生物学活性测定时间相同。结论 长效EPO在小鼠体内生物学活性测定的采血时间为d 4,检测方法的建立应参照临床用药剂量和产品说明书,并通过方法适用性考察。

关键词: 长效促红细胞生成素, 网织红细胞法, 生物学活性, 采血时间, 小鼠

Abstract: Objective To investigate the pharmacodynamics of long-acting erythropoietin (EPO) in mice and explore a proper method for an in vivo biological activity detection of long-acting EPO. Methods According to the reticulocyte assay method for determining the biological activity of EPO specified in the Chinese Pharmacopoeia, mice were subcutaneously injected with different doses of long-acting EPO or short-acting EPO. The percentage of reticulocytes in the mouse blood was observed for ten consecutive days after administration. A well-conceived dosing regimen and blood sampling schedule were designed to establish an in vivo method for determining the biological activity of long-acting EPO and to conduct the biological activity assay of long-acting EPO. Results According the bio-statistical model using the (3. 3) parallel line method, the in vivo biological activities of three batches of long-acting EPO were 94% (FL% 23%), 94% (FL% 17%) and 92% (FL% 15%) respectively when mice were given low, medium and high doses of 0.2, 0.4 and 0.8 IU per mouse, and day 4 was the optimal blood sampling time, as with short-acting EPO. Conclusion The blood-sampling time for in vivo biological activity assay of long-acting EPO is on day 4. A method should be established based on clinical dosage and product instructions and verified by tests on its applicability.

Key words: Long-Acting Erythropoietin, Reticulocyte Method, Biological Activity Assay, Blood Sampling Time, Mice

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