重组人促红素体内、体外生物学活性差异成因分析

目的分析造成重组人促红素(rHuEPO)体内、体外生物学活性差异的原因。方法按《中国药典》三部(2005版)方法检测rHuEPO样品体内、体外生物学活性,并通过等电聚焦电泳分析、唾液酸含量、纯度、N-糖链糖基化和相对分子质量检测,探讨样品体内、体外生物学活性产生差异的原因。结果体内、体外生物学活性有差异的rHuEPO样品中,存在糖链末端N-乙酰神经氨酸残基不完整的rHuEPO成分。纯度、N-糖链糖基化和相对分子质量检测结果未见异常。结论为提高rHuEPO产品质量,应在生产过程中有效去除N-乙酰神经氨酸残基不完整的rHuEPO。

Reason for Discrepancy between In Vitro and In Vivo Biological Activities of Re combinant Human Erythropoietin

Objective To analyze the reason for discrepancy between in vitro and in vivo biological activities of recombinant human erthropoietin(rHuEPO). Methods Take samples from rHuEPO for determination of in vitro and in vivo biological activities,as well as for isoelectric focusing elecrophoresis and for determination of sialic acid content,purity,N-glycosylation and relative molecular mass,according to the requirements in Chinese Pharmacopoeia (2005 edition). Results Incomplete N-acetylneuraminate components were observed in rHuEPO samples with discrepancy between in vitro and in vivo biological activities.However,no abnormalities were observed in purity,N-glycosylation or relative molecular mass. Conclusion The rHuEPO with incomplete N-acetylneuraminate components shall be removed effectively during production to improve the quality of final product.