Sluzky V, Tamada J A, Klibanov A M, Langer R
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9377-81. doi: 10.1073/pnas.88.21.9377.
The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.
基于蛋白质的药物（如胰岛素）的稳定性对于其生产、储存和递送至关重要。为了了解胰岛素在水溶液中的聚集机制，研究了搅拌速率、界面相互作用和胰岛素浓度对整体聚集速率的影响。采用紫外吸收光谱、高效液相色谱和准弹性光散射分析来监测聚集反应并识别中间物种。反应分两个阶段进行；胰岛素在较高浓度下稳定性增强。采用所提出的动力学方案进行数学建模，以确定可能的反应途径并解释在较高胰岛素浓度下更高的稳定性。
