稳定蛋白质药品通过像类型的zwitterionsons稳定蛋白质药品
Ai Tajiri1, Takeru Ishizaki1, Takahiro Takekiyo2
1Faculty of Biological Science and Technology, Institute of Science and Engineering, Kanazawa University, Kakuma-Machi, Kanazawa, 920-1192, Japan.
Physical chemistry chemical physics : PCCP
|February 6, 2025
概括
伊米达-碳酸盐zwitterion OE2imC3C稳定胰岛素的结构和功能在热和震动下. 60%重量%的溶液有效地防止了聚合,并维持了胰岛素.
科学领域:
- 生物化学 生物化学
- 材料科学 材料科学 材料科学
- 制药科学 制药科学
背景情况:
- 蛋白质制药在制造和分销过程中容易受到热和机械应力的损伤.
- 像OE2imC3C这样的伊米达-碳酸盐zwitterions已经显示出稳定血红蛋白的潜力,例如cytochrome c.
- 在保持治疗性蛋白质的结构完整性和功能方面,OE2imC3C的有效性仍然在很大程度上未被探索.
研究的目的:
- 研究OE2imC3C作为蛋白质药品稳定剂的潜力.
- 评估OE2imC3C在压力条件下对胰岛素结构稳定性和生物活性的影响.
- 为了确定OE2imC3C的最佳度以有效稳定蛋白质.
主要方法:
- 具有不同度的OE2imC3C (20%重量,40%重量和60%重量%) 的胰岛素溶液经过震动 (1000rpm) 和加热 (80°C).
- 通过监测二级结构的变化来评估结构完整性.
- 通过细胞增殖试验来评估功能活性.
主要成果:
- 60%重量%OE2imC3C溶液中的胰岛素在和加热后保持其折叠结构并表现出正常功能.
- 相比之下,20%重量OE2imC3C溶液中的胰岛素和40%重量OE2imC3C溶液中的胰岛素在相同条件下显示出二次结构的改变.
- 这项研究表明,OE2imC3C对胰岛素具有度依赖的稳定作用.
结论:
- 60%重量%的OE2imC3C溶液显示出稳定胰岛素等蛋白质制药对热和机械应力的显著潜力.
- OE2imC3C可以保留胰岛素的结构和功能,这表明它在制药配方和运输中的实用性.
- 对OE2imC3C配方的进一步研究可能会导致敏感的基于蛋白质的治疗药物的稳定性得到改善.
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