Vrkljan M, Foster T M, Powers M E, Henkin J, Porter W R, Staack H, Carpenter J F, Manning M C
School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262.
Pharm Res. 1994 Jul;11(7):1004-8. doi: 10.1023/a:1018935420680.
Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein.
比浊法或光散射测定法可用于确定蛋白质制剂中的聚集程度。以低分子量尿激酶（LMW-UK）作为模型蛋白，评估了聚合物添加剂对热诱导聚集的影响。先前的研究表明，在60摄氏度热处理条件下，LMW-UK最初会变性，展开的蛋白缔合形成可溶性聚集体。最终，这些聚集体进一步缔合形成沉淀。研究了聚合物对初始聚集阶段的影响。发现羟乙基（heta）淀粉、聚乙二醇4000和明胶是有效的、浓度依赖性的聚集抑制剂，而聚乙烯吡咯烷酮（PVP）和聚乙二醇300则无效。总体而言，聚合物添加剂对热应激LMW-UK稳定性的影响可通过溶质从蛋白质表面的优先排除来解释。
