process for stabilizing proteins in a freezing and lyophilizing process or during storage at low temperatures, storage form and pharmaceutical composition.

摘要

Improved method for inhibiting formation of protein aggregates in a reconstituted lyophilizate of a pharmaceutical protein-containing composition comprises dissolving the protein in an aqueous solution that contains potassium phosphate (I) as buffering agent and has potassium to sodium ion ratio 10:1 or greater. The solution is frozen, thawed, divided into containers, each containing a dose for injection, then lyophilized. Independent claims are also included for the following: (1) thawable, solid storage form of a protein, with low content of aggregates, that is essentially amorphous, contains a frozen solution of protein in (I) buffer and has K:Na ion ratio at least 10:1; and (2) a pharmaceutical composition comprising a protein in aqueous buffer of pH 6-8 that contains (I) as buffering agent, has K:Na ion ratio at least 10:1 and has buffer concentration 10-300 mM.