Pharmaceutical formulation
AssigneeNovo Nordisk A/S
InventorsHans Holmegaard S.o slashed.rensen, Lars Skriver, Annie Rassing Hoelgaard
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Abstract
A pharmaceutical preparation comprising a growth hormone and histidine or a derivative of histidine as additive or buffering substance shows a very high stability against deamidation, oxidation and cleavage of peptide bonds. The stability of the product allows for the storing and shipment thereof in a lyophilized state or in the form of a dissolved or re-dissolved preparation at ambient temperature. Crystallization of growth hormone in the presence of histidine or a derivative thereof gives rise to a higher yield of crystals having a higher purity than known methods.
Claims21
A pharmaceutical composition in the form of a lyophilized powder comprising a growth hormone or a derivative thereof and histidine or histidine derivative, in which said derivative is selected from the group consisting of an amide or ester of histidine, imidazole, imidazole-4-acetic acid, des-amino-His, His--Leu, His--Ala, His--Lys, and His--Phe, in an amount of from about 0.1 to about 12 mg histidine per mg of growth hormone or a derivative thereof.
A pharmaceutical composition in the form of a buffered aqueous solution comprising a growth hormone or derivative thereof buffered with histidine or histidine derivative, in which said derivative is selected from the group consisting of an amide or ester of histidine, imidazole, imidazole-4-acetic acid, des-amino-His, His--Leu, His--Ala, His--Lys, and His--Phe at a concentration from about 1 mM to about 100 mM.
Crystalline growth hormone or a derivative thereof comprising histidine or histidine derivative, in which said derivative is selected from the group consisting of an amide or ester of histidine, imidazole, imidazole-4-acetic acid, des-amino-His, His--Leu, His--Ala, His--Lys, and His--Phe and a cation.
Dependencies are inferred from the claim text.