|Title:|| Pharmaceutical formulation of human-growth hormone pretreated with zinc salt|
|Abstract:||A pharmaceutical formulation comprising a growth hormone pretreated with zinc and optionally lysine or calcium ions 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 formulation at ambient temperature.|
|Inventor(s):|| S.o slashed.rensen; Hans Holmegaard (Virum, DK), Olsen; Ole Hvilsted (Br.o slashed.nsh.o slashed.j, DK), Thim; Lars (Gentofte, DK), Thorkild; Christensen (Aller.o slashed.d, DK), Balschmidt; Per (Esperg.ae butted.rde, DK) |
|Assignee:|| Novo Nordisk A/S (Bagsvaerd, DK) |
|Filing Date:||Jul 23, 1998|
|Claims:||1. A pharmaceutical formulation comprising a human growth hormone pretreated with zinc salt for at least one hour before addition of other components to the formulation and optionally containing lysine or calcium ion. |
2. The formulation according to claim 1, futher comprising a buffered aqueous solution.
3. The formulation according to claim 1, wherein said formulation has a pH between about 2 to about 9.
4. The formulation according to claim 1, wherein the concentration of zinc salt is between about 0.01-2 mM.
5. The formulation according to claim 1, further comprising salt and saccharide.
6. A method of preparing the pharmaceutical formulation according to claim 1, comprising (a) dissolving growth hormone in a solution comprising zinc chloride and optionally lysine or calcium ions, (b) letting the solution of (a) stand for at least one hour, (c) adding benzyl alcohol to the solution of step (b) and (d) optionally adjusting the pH to from about 2 to about 9.
7. The method according to claim 6, which further comprises after step (b) and before step (c) subjecting the solution of step (b) to gel filtration chromatography.
8. The method according to claim 6, further comprising adding salts and an excipient, filling the solution into a container and lyophilizing said solution.
9. A method for treating a patient having a disorder affectable by growth hormone deficiency, comprising administering to said patient the formulation of claim 1.