在冷干燥单克隆抗体配方中的放松过程――糖度的作用
N S Krishna Kumar1, Zhiyi Lin2, Yunhua Chen3
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Molecular pharmaceutics
|June 11, 2025
概括
单克隆抗体 (mAb) 与糖的最佳比率用于稳定冷干燥蛋白质配方是 4:1. 这种比率确保了抗体本质结构的最佳保留,并影响了热和放松行为.
科学领域:
- 生物物理化学 生物物理化学
- 蛋白质稳定 蛋白质稳定
- 配方科学科学 配方科学
背景情况:
- 糖糖是冷干燥蛋白质配方中常见的稳定剂.
- 了解稳定剂与蛋白质比率的影响对于配方稳定性至关重要.
研究的目的:
- 为了研究单克隆抗体 (mAb) 与糖的重量比对冷干燥配方特性的影响.
- 为了确定保持mAb原生结构和配方稳定性的最佳比例.
主要方法:
- 差分扫描热量计 (DSC) 用于测量热行为.
- 放松动态的介电光谱学.
- 固态核磁共振 (NMR) 用于1H T1放松.
- 红外光谱学用于二次结构保留.
主要成果:
- 降低mAb与糖的比率降低了玻璃过渡温度 (DSC).
- 放松时间 (α,β,γ) 和1H T1放松时间因比例而异.
- 在 4:1 mAb-to-sucrose比率下观察到最佳的本地类二次结构保留.
- 在1:1或更低的比率下没有检测到相位分离.
结论:
- mAb与糖的重量比率显著影响冷制剂的热和放松性能.
- 4:1的mAb-to-sucrose比率是保持单克隆抗体原生结构的最佳.
- 这些发现提供了关于固态抗体-糖糖系统行为的见解.
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