Mechanisms for Success or Failure of Excipients and Protein-Stabilizers

赋形剂和蛋白质稳定剂成功或失败的机制

• 批准号: 9816975
• 负责人: Theodore Randolph
• 金额: $ 35.89万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9816975&HistoricalAwards=false
• 关键词: Mechanisms; Success; Failure; Excipients; Protein

The objective of this project is to advance the understanding of the mechanisms for success and failure of excipients as protein stablilizers in solution, during freezing, drying, and reconstitution. Questions to be addressed during the course of the project include: (1) what are the implications of protein surface modification on protein stabilizer interactions and the capacity of such excipients to protect proteins during processing; (2) when and how do surfactants stabilize proteins in solution, and during freezing, drying, and reconstitution; (3) can the solution thermodynamic model developed by Timasheff and co-workers be used to explain the inhibition of protein chemical degradation kinetics by preferentially excluded solutes; and (4) what processes can account for apparent time-dependent degradation processes in samples stored in dried solids at temperatures below formulation glass transition temperatures.

本项目的目的是促进对辅料作为蛋白质稳定剂在溶液中、冷冻、干燥和重建过程中成败机理的理解。项目期间要解决的问题包括：(1)蛋白质表面修饰对蛋白质稳定剂相互作用以及这种辅料在加工过程中保护蛋白质的能力有何影响；(2)表面活性剂何时及如何稳定溶液中的蛋白质，以及在冷冻、干燥和重组过程中；(3)Timasheff及其同事开发的溶液热力学模型能否解释优先排除溶质对蛋白质化学降解动力学的抑制作用；以及(4)在低于配方玻璃化转变温度的干燥固体中存储的样品中，哪些过程可以解释明显的依赖时间的降解过程。