制剂组成对抗表皮生长因子单克隆抗体稳定性的影响

目的: 研究制剂组成对抗表皮生长因子(epidermal growth factor,EGF)单克隆抗体稳定性的影响。 方法: 应用体积排阻色谱、离子交换色谱、酶联免疫反应对加速试验条件下的单克隆抗体的降解、多聚体的产生、表面电荷的不均一性和活性进行测定。 结果: 在pH相同的制剂中缓冲组分是稳定单克隆抗体的关键因素,制剂溶液中其他保护成分如非离子型表面活性剂的浓度、糖的类型及浓度对单克隆抗体稳定性有一定的影响。 结论: 选择合适的制剂组分与浓度能够有效地提高单克隆抗体的稳定性,在单克隆抗体药物制剂工艺开发中,对制剂组成进行优化是必要的。

Objective: To study the effect of formulation components on stability of anti-EGF monoclonal antibody. Methods: The aggregation,degradation,surface charge heterogeneity and activity of monoclonal antibody in stressed test have been detected by size exclusion chromatography,ion exchange chromatography and enzyme-linked immunosorbent assay(ELISA). Results: The buffer components in formulations with the same pH were the key factor to stabilize monoclonal antibody;the kind and concentration of other protective components such as non-ion surfactant and sugars also had a certain impact on its stability. Conclusion: Selection of optimal kind and concentration of formulation components was effective to enhance the stability of monoclonal antibody,and it was necessary to optimize the composition of formulation in the development process of monoclonal antibody-based drugs formulation.