Composition for sustained release of human growth hormone

• US 5,891,478 A
• Filed: 03/02/1998
• Issued: 04/06/1999
• Est. Priority Date: 12/02/1992
• Status: Expired due to Fees

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Ganmukhi, Medha M., Auer, Henry, Bernstein, Howard, Khan, M. Amin, Johnson, OluFunmi Lily
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/033,193
• Time in Patent Office: 400 Days
• Field of Search: 424/423, 424/426, 424/489, 424/499, 424/500, 424/501, 424/502, 514/21, 530/399, 530/839
• US Class Current: 424/502
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 530/839 Nerves; brain
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer

Abstract

The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Claims

1. A method of forming a composition for the sustained release of human growth hormone from a polymeric matrix comprising the steps of:

a) forming a mixture comprising a biocompatible polymer, particles of metal cation-complexed hGH and a polymer solvent; and

b) solidifying the mixture to form a polymeric matrix containing a dispersion of said hGH particles.

2. The method of claim 1 wherein step (a) further comprises the steps of:

(i) forming droplets of the mixture; and

(ii) freezing the droplets of step (i), prior to the solidifying of step (b).

3. The method of claim 2 wherein the polymer is solidified by removing the polymer solvent by extraction with a polymer non-solvent.

4. The method of claim 1 wherein the biocompatible polymer is selected from the group consisting of:

poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acids)s, polycaprolactones, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polycyanoacrylates, poly(p-dioxanone)s, poly(alkylene oxalate)s, biodegradable polyurethanes, blends and copolymers thereof.

5. The method of claim 4 wherein the biocompatible polymer is poly(lactide-co-glycolide).

6. The method of claim 1 wherein the metal cation-complexed human growth hormone contains a multivalent metal cation component.

7. The method of claim 6 wherein the multivalent metal cation component is zinc.

8. The method of claim 7 wherein the particles of hGH have a zinc to hGH molar ratio between 4:

1 and 100;

1.

9. The method of claim 1 further comprising the step of dispersing a second metal cation component in the mixture wherein the second metal cation is not complexed to said human growth hormone.

10. The method of claim 9 wherein the second metal cation component is zinc carbonate.

11. The method of claim 1 wherein the polymeric matrix is in the form of microparticles.

12. The method of claim 1 wherein the final proportion of human growth hormone in the sustained release composition is between 10 and 30 weight percent.