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阐明人类胰岛素在固态中的降解途径
Andrew Fagan1, Lorraine M Bateman2,3,4, Joseph P O'Shea2
1SSPC, the SFI Centre for Pharmaceutical Research, School of Pharmacy, University College Cork, Cork, T12 YT20 Ireland.
概括
开发用于固态降解的分析方法对于口服输送至关重要. 这项研究对胰岛素的基准技术进行了比较,揭示了固态胰岛素中的除氧化和聚合途径.
科学领域:
- 制药科学 制药科学
- 分析化学 分析化学
- 生物化学 生物化学
背景情况:
- 由于的不稳定性,口服的输送面临挑战.
- 固态降解途径与溶液状态降解途径不同.
- 胰岛素作为研究降解的模型.
研究的目的:
- 开发和基准分析技术,用于研究固态胰岛素降解.
- 将固态降解路径与溶液中的降解路径进行比较.
- 阐明固态胰岛素中脱和聚合的机制.
主要方法:
- 化学化,除化和聚合胰岛素样品的制备.
- 基准测量循环二重化谱学,逆相HPLC和大小排除色谱学.
- 使用这些方法分析固态降解胰岛素 (60°C,75%RH).
- 用dithiothreitol进行降低性二硫化物键裂解,用于链分离.
主要成果:
- 在固态胰岛素中没有观察到任何展开.
- 在固态胰岛素中检测到显著的脱化和共价聚合.
- 硫化物键裂解促进了对除化和聚合机制的评估.
结论:
- 固态降解分析的既定分析方法. 固态降解分析.
- 确定了除化和共价聚合作为固态胰岛素的关键降解途径.
- 提供了一种评估固态胰岛素降解机制的新方法.
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