疏水盐作为降低单克隆抗体浓缩溶液黏度的辅料的构效关系。
Structure-activity relationship for hydrophobic salts as viscosity-lowering excipients for concentrated solutions of monoclonal antibodies.
机构信息
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Pharm Res. 2012 Nov;29(11):3102-9. doi: 10.1007/s11095-012-0802-9. Epub 2012 Jun 13.
PURPOSE
To discover, elucidate the structure-activity relationship (SAR), and explore the mechanism of action of excipients able to drastically lower the viscosities of concentrated aqueous solutions of humanized monoclonal antibodies (MAbs).
METHODS
Salts prepared from hydrophobic cations and anions were dissolved into humanized MAbs solutions. Viscosities of the resulting solutions were measured as a function of the nature and concentration of the salts and MAbs.
RESULTS
Even at moderate concentrations, some of the salts prepared herein were found to reduce over 10-fold the viscosities of concentrated aqueous solutions of several MAbs at room temperature.
CONCLUSIONS
To be potent viscosity-lowering excipients, the ionic constituents of the salts must be hydrophobic, bulky, and aliphatic. A mechanistic hypothesis explaining the observed salt effects on MAb solutions' viscosities was proposed and verified.
目的
发现、阐明结构-活性关系（SAR），并探索能够显著降低人源化单克隆抗体（mAb）浓水溶液粘度的赋形剂的作用机制。
方法
将由疏水阳离子和阴离子制备的盐溶解在人源化 mAb 溶液中。测量所得溶液的粘度作为盐和 mAb 的性质和浓度的函数。
结果
即使在中等浓度下，本文制备的一些盐被发现可将几种 mAb 的浓水溶液在室温下的粘度降低 10 倍以上。
结论
作为有效的降低粘度赋形剂，盐的离子成分必须具有疏水性、大体积和脂肪族特性。提出并验证了一个解释观察到的盐对 mAb 溶液粘度影响的机制假说。
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