| 摘要 |
Stabilized liquid pharmaceutical composition (I) comprising a polypeptide or its variant, an amino acid base comprising arginine, lysine, aspartic acid or glutamic acid and a buffering agent. New stabilized liquid pharmaceutical composition (I) comprises: (a) an active agent consisting polypeptide (or one of its variants), exhibiting aggregate formation during storage in a liquid formulation; (b) an amino acid base present in an amount sufficient to decrease aggregate formation of the polypeptide or its variant during storage of the composition, the amino acid base comprising at least one amino acid selected from arginine, lysine, aspartic acid and glutamic acid; and (c) a buffering agent selected from an acid free of its salt forms and/or an acid in its salt form. Independent claims are also included for: (1) a stabilized liquid pharmaceutical composition comprising interleukin-2 (IL-2) or one of its variants, arginine in its free base form (150-350 mM) and succinic acid substantially free of its salt form (80-190 mM); (2) a stabilized liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or one of its variants, arginine in its free base form (175-325 mM) and succinic acid substantially free of its salt form (80-190 mM); (3) a stabilized liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or one of its variants, arginine in its free base form (175-400 mM) and citric acid substantially free of its salt form (40-200 mM); and (4) a method for increasing the stability of a polypeptide or one of its variants in a liquid pharmaceutical composition, where the polypeptide or it variant exhibits aggregate formation during storage in a liquid formulation, by incorporating into the composition an amino acid base in an amount sufficient to decrease aggregate formation of the polypeptide or one of its variants and a buffer selected from acids free of their salt forms, acids in their salt forms and a mixture of an acids and its salt form, the amino acid base comprising at least one amino acid selected form arginine, lysine, aspartic acid and glutamic acid. |
