Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA.
Pharm Res. 2011 Jul;28(7):1552-60. doi: 10.1007/s11095-011-0388-7. Epub 2011 May 15.
To assess the effect of sugar molecules on solution viscosity at high protein concentrations.
A high throughput dynamic light scattering method was used to measure the viscosity of monoclonal antibody solutions. The effects of protein concentration, type of sugar molecule (trehalose, sucrose, sorbitol, glucose, fructose, xylose and galactose), temperature and ionic strength were evaluated. Differential scanning fluorimetry was used to reveal the effect of the same sugars on protein stability and to provide insight into the mechanism by which sugars increase viscosity.
The addition of all seven types of sugar molecules studied result in a significant increase in viscosity of high concentration monoclonal antibody solutions. Similar effects of sugars were observed in the two mAbs examined; viscosity could be reduced by increasing the ionic strength or temperature. The effect by sugars was enhanced at higher protein concentrations.
Disaccharides have a greater effect on the solution viscosity at high protein concentrations compared to monosaccharides. The effect may be explained by commonly accepted mechanisms of interactions between sugar and protein molecules in solution.
评估高浓度蛋白质溶液中糖分子对溶液黏度的影响。
采用高通量动态光散射法测量单克隆抗体溶液的黏度。评估了蛋白质浓度、糖分子类型（海藻糖、蔗糖、山梨糖醇、葡萄糖、果糖、木糖和半乳糖）、温度和离子强度的影响。差示扫描荧光法用于揭示相同糖对蛋白质稳定性的影响，并深入了解糖增加黏度的机制。
研究的七种糖分子的添加都导致高浓度单克隆抗体溶液的黏度显著增加。在两种 mAb 中观察到相似的糖效应；通过增加离子强度或温度可以降低黏度。在较高的蛋白质浓度下，糖的作用增强。
与单糖相比，二糖在高蛋白质浓度下对溶液黏度的影响更大。该作用可以通过溶液中糖和蛋白质分子之间的相互作用的公认机制来解释。
