Low-molecular-weight (LMW) aggregate is a critical determinant of subsequent protein aggregation, but the aggregate growth kinetics of solid proteins have not been fully characterized. In this study, the high-molecular weight (HMW) aggregate formation process for solid-state proteins and the relationship between aggregation and physical properties of tablets were evaluated using proteins with various initial aggregate ratios. Quantitative changes in monomers, LMW aggregates, and HMW aggregates during storage were measured. The monomer amount decreased uniformly for all proteins. Proteins with low initial LMW aggregates showed remarkable increases in LMW aggregates but little increases in HMW aggregates during storage. Proteins with high initial LMW aggregates showed decreases in LMW aggregates but remarkable increases in HMW aggregates. A correlation analysis and logistic regression indicated that HMW aggregate formation depended on the initial quantity of LMW aggregates. Furthermore, the initial LMW aggregate ratio was related to the disintegratability of protein-containing tablets after storage. These results provide novel insight into solid-state protein aggregation and may guide the prediction of the long-term quality of solid protein-containing pharmaceuticals and foods without storage.

中文翻译：

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低分子量聚集体对固态蛋白在储存过程中聚集体生长动力学和物理性质的影响。

低分子量（LMW）聚集体是后续蛋白质聚集的关键决定因素，但尚未完全表征固体蛋白质的聚集体生长动力学。在这项研究中，固态蛋白质的高分子量（HMW）聚集体形成过程以及片剂的聚集与物理性质之间的关系使用各种初始聚集体比率的蛋白质进行了评估。测量了储存期间单体，LMW聚集体和HMW聚集体的定量变化。所有蛋白质的单体量均一下降。具有低初始LMW聚集体的蛋白质在存储过程中显示LMW聚集体显着增加，但HMW聚集体几乎没有增加。具有高初始LMW聚集体的蛋白质显示LMW聚集体减少，但HMW聚集体显着增加。相关分析和逻辑回归表明，HMW聚集体的形成取决于LMW聚集体的初始数量。此外，初始LMW聚集比与储存后含蛋白质的片剂的崩解性有关。这些结果提供了对固态蛋白质聚集的新见解，并可能指导对不含储存固体蛋白质的药物和食品的长期质量的预测。