本课题拟通过具有不同表面疏水区域、表面带电性质等指标的蛋白质聚集体，构建蛋白质聚集体关键指标与蛋白质构象稳定性参数（二、三、四级构象参数）、胶体稳定性参数（蛋白质相互作用因子kD、第二维利系数B2等）的相关关系，揭示蛋白质聚集体与蛋白质构象稳定性、胶体稳定性的内在联系，并基于蛋白质聚集体关键指标构建蛋白质构象、胶体稳定性变化过程的模型，指导蛋白药物制剂工艺和储存条件的选择。通过研究蛋白药物生物稳定性参数(PK/PD参数、抗药性抗体水平、T细胞免疫应答参数)变化与蛋白质聚集体关键指标的关系，寻找蛋白质聚集体与蛋白制剂体内药效、不良反应的关联。通过调整和控制蛋白质聚集体关键指标以优化蛋白质稳定性，结合实证相图等可视化方法，实现高通量筛选蛋白多肽类药物制剂处方。进一步完成蛋白质在溶液状态下的稳定性研究方法探讨及体内外相关性研究，为蛋白制剂制备、储存以及体内活性的稳定性研究提供理论依据。

Intends to control and generate protein aggregates with different key indicators (surface hydrophobicity, surface electric property) through pharmaceutical methods, and construct the relationships between key indicators of protein aggregates and protein conformational stability parameters (secondary, tertiary, fourth conformational parameters) or colloidal stability parameters (protein interaction parameter kD, second virial coefficient B2). Reveal the intrinsic link of protein aggregates and protein conformational or colloidal stability, construct the change process models of protein conformational and colloidal stability based on key indicators of protein aggregates. To obtain intrinsic links of protein aggregates and efficacy or side effect, we intend to construct correlation model between biological stability parameters (PK/PD, anti-drug antibody level and T-cell immune response parameters) and key indicators of protein aggregates as well. In combination with empirical phase diagram visualization method, the optimization of protein stability and high-throughput screening of protein prescription could be achieved by adjusting these key indicators. Further fulfill the stability study of protein solution in vivo, and investigate correlation between in vivo and vitro. To provide a theoretical basis of stability for storage as well as in vivo activity of protein solution.