Controlled release of metal cation-stabilized interferon

• US 6,780,434 B2
• Filed: 03/06/2002
• Issued: 08/24/2004
• Est. Priority Date: 07/25/1994
• Status: Expired due to Fees

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Khan, M. Amin, Bernstein, Howard, Tracy, Mark A.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US10/092,365
• Publication Number:
  US 20030031716A1
• Time in Patent Office: 902 Days
• Field of Search: 424/486-488, 424/499, 424/501, 424/422-23, 424/426, 530/814-15
• US Class Current: 424/487
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 14/56 IFN-alpha

Abstract

This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

Claims

1. A composition for the controlled release of interferon from a polymeric matrix, comprising:

a) a biodegradable polymer 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 acid)s, polycaprolactone, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polyacetals, polycyanoacrylates, polyetheresters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, biodegradable polyurethanes, blends thereof and copolymers thereof; and

b) particles of metal cation-complexed interferon, wherein said particles are dispersed within the biodegradable polymer and the interferon is present from about 0.1% (w/w) to about 50% (w/w) of the dry weight of the composition.

2. The composition of claim 1 wherein the interferon is present from about 0.1 (w/w) to about 30% (w/w) of the dry weight of the composition.

3. The controlled release composition of claim 1 wherein the metal cation-to-interferon molar ratio is from about 1:

1 and 10;

1.

4. The controlled release composition of claim 3 wherein the metal cation to interferon molar ratio is about 2:

1.

5. The controlled release composition of claim 1 wherein the metal cation of said metal cation-complexed interferon contains at least one type of biocompatible multivalent cation, wherein said cation is not significantly oxidizing to interferon.

6. The controlled release composition of claim 5 wherein said multivalent cation is selected from the group consisting of Zn⁺², Ca⁺², Cu⁺², Mg⁺² and combinations thereof.

7. The controlled release composition of claim 1 wherein the interferon is interferon-α

.

8. A controlled release composition of claim 1 wherein the biodegradable polymer is a poly(lactide-co-glycolide).

9. A controlled release composition of claim 1 further comprising a second metal cation component, wherein the second metal cation component is not contained in said interferon particles, and wherein the second metal cation component is dispersed within the biocompatible polymer to modulate the release of interferon from the polymeric matrix.

10. A controlled release composition of claim 9 wherein the second metal cation component is selected from the group consisting of magnesium hydroxide, magnesium carbonate, calcium carbonate, zinc carbonate, magnesium acetate, zinc acetate, magnesium sulfate, zinc sulfate, magnesium chloride, zinc chloride, zinc citrate, magnesium citrate and a combination thereof.