Thermal Stability of Low Molecular Weight Urokinase During Heat Treatment. II. Effect of Polymeric Additives.

Autor: Vrkljan, Michael, Foster, Thomas, Powers, Michael, Henkin, Jack, Porter, William, Staack, Harold, Carpenter, John, Manning, Mark
Zdroj: Pharmaceutical Research; Jul1994, Vol. 11 Issue 7, p1004-1008, 5p
Abstrakt: 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°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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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