Hong Taehun, Iwashita Kazuki, Shiraki Kentaro
Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
Curr Protein Pept Sci. 2018;19(8):746-758. doi: 10.2174/1389203719666171213114919.
Viscosity of protein solution is one of the most troublesome issues for the high-concentration formulation of protein drugs. In this review, we summarize the practical methods that suppress the viscosity of protein solution using small molecular additives. The small amount of salts decreases the viscosity that results from electrostatic repulsion and attraction. The chaotrope suppresses the hydrophobic attraction and cluster formation, which can lower the solution viscosity. Arginine hydrochloride (ArgHCl) also suppresses the solution viscosity due to the hydrophobic and aromatic interactions between protein molecules. The small molecular additives are the simplest resolution of the high viscosity of protein solution as well as understanding of the primary cause in complex phenomena of protein interactions.
蛋白质溶液的粘度是蛋白质药物高浓度制剂中最棘手的问题之一。在本综述中，我们总结了使用小分子添加剂抑制蛋白质溶液粘度的实用方法。少量盐可降低由静电排斥和吸引导致的粘度。离液剂可抑制疏水吸引和聚集体形成，从而降低溶液粘度。盐酸精氨酸（ArgHCl）也可因蛋白质分子间的疏水和芳香相互作用而抑制溶液粘度。小分子添加剂是解决蛋白质溶液高粘度问题的最简单方法，同时也有助于理解蛋白质相互作用复杂现象的主要原因。
