Faculté de Pharmacie, Université Paris-Sud, UMR CNRS 8612, Châtenay-Malabry Cedex, France.
Eur J Pharm Biopharm. 2010 Nov;76(3):351-6. doi: 10.1016/j.ejpb.2010.08.002. Epub 2010 Aug 16.
This study of highly concentrated polyvalent immunoglobulin solutions, IgG, aimed at analyzing the relationships between protein concentration and aggregation on the one hand and viscosity on the other hand. Viscosity variations as a function of IgG concentration showed two well-defined behaviours: a Newtonian behaviour for low-concentrated solutions and a shear-thinning behaviour for highly concentrated ones. The viscosity data fitted very well with the Mooney model, suggesting the absence of intermolecular interactions in the IgG solutions that behaved like a non-interacting suspension of hard particles. The polyclonal nature of IgG seems to prevent intermolecular interaction. The shape factor, determined from Mooney fitting, revealed a non-spherical shape of the polyclonal IgG molecules. The rheological properties were also correlated with the injection force (F) through hypodermic needles by syringeability tests. Here, F was mainly affected by three parameters: the solution viscosity, the injection flow rate, and the needle characteristics. In fact, syringeability tests showed that F increased with IgG concentration and flow rate and decreased with the internal diameter of the needle. A zone for optimal injection conditions was then identified taking into account the different affecting parameters and mainly a maximum force for manual injection, which was fixed at 30N.
本研究针对高浓度多价免疫球蛋白溶液（IgG）展开，旨在分析蛋白浓度与聚集之间的关系，以及浓度与粘性之间的关系。IgG 浓度与粘性变化之间存在两种明确的关系：低浓度溶液呈牛顿行为，高浓度溶液呈剪切稀化行为。粘度数据与 Mooney 模型拟合得非常好，表明 IgG 溶液中不存在分子间相互作用，这些溶液的行为类似于非相互作用的硬颗粒悬浮液。IgG 的多克隆性质似乎阻止了分子间的相互作用。从 Mooney 拟合中确定的形状因子表明，多克隆 IgG 分子的形状是非球形的。流变性能也通过皮下针注射器的可注射性测试与注射力（F）相关联。在这里，F 主要受到三个参数的影响：溶液粘度、注射流速和针头特性。事实上，可注射性测试表明，F 随着 IgG 浓度和流速的增加而增加，随着针头内径的减小而减小。然后，考虑到不同的影响参数，特别是手动注射的最大力（固定为 30N），确定了一个最佳注射条件区域。
