Details for Patent: 6,165,508
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| Title: | Controlled release of metal cation-stabilized interferon |
| 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. |
| Inventor(s): | Tracy; Mark A. (Arlington, MA), Bernstein; Howard (Cambridge, MA), Khan; M. Amin (Downington, PA) |
| Assignee: | Alkermes Controlled Therapeutics, Inc. (Cambridge, MA) |
| Filing Date: | Mar 07, 1997 |
| Application Number: | 08/765,558 |
| Claims: | 1. A composition for the controlled release of interferon from a polymeric matrix, comprising: a) a biocompatible polymer; and b) particles of metal cation-complexed interferon, wherein said particles are dispersed within the biocompatible polymer. 2. A controlled release composition of claim 1 wherein the biocompatible polymer is a biodegradable polymer. 3. A controlled release composition of claim 2 wherein the biodegradable 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 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 and copolymers thereof. 4. A controlled release composition of claim 2 wherein said polymer comprises poly(lactide-co-glycolide). 5. A controlled release composition of claim 1 wherein the biocompatible polymer is non-biodegradable. 6. A controlled release composition of claim 5, further comprising a pore forming agent which is dispersed within the non-biodegradable polymer. 7. A controlled release composition of claim 5 wherein the non-biodegradable polymer is selected from the group consisting of non-biodegradable polyurethanes, polyacrylates, poly(ethylene-vinyl acetates), poly(acyl-substituted cellulose acetates), polysaccharides, polystyrenes, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chlorosulphonated polyolefins, polyethylene oxides, blends and copolymers thereof. 8. A controlled release composition of claim 1 wherein said polymer is selected from the group consisting of blocked polymers, unblocked polymers and blends thereof. 9. A 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. 10. A controlled release composition of claim 9 wherein said multivalent cation is selected from the group consisting of Zn.sup.+2, Ca.sup.+2, Cu.sup.+2, Mg.sup.+2 and combinations thereof. 11. 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. 12. A controlled release composition of claim 11 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. 13. A method for forming a composition for the controlled release of interferon, comprising the steps of: a) dissolving a biocompatible polymer in a polymer solvent to form a polymer solution; b) dispersing metal cation-complexed interferon particles in the polymer solution; and c) solidifying the polymer to form a polymeric matrix containing a dispersion of said interferon particles. 14. A method of claim 13 wherein the metal cation of the metal cation-complexed interferon contains at least one type of biocompatible multivalent cation, which is not significantly oxidizing to interferon. 15. A method of claim 14 wherein the multivalent cation is selected from the group consisting of Zn.sup.+2, Ca.sup.+2, Mg.sup.+2, Cu.sup.+2 and a combination thereof. 16. A method of claim 13 further comprising the step of dispersing a second metal cation component within the polymer solution, wherein the second metal cation component is not contained in said interferon particles. 17. A method of claim 16 wherein the second metal cation component is multivalent. 18. A method of claim 17 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. 19. A composition for the controlled release of interferon from a polymeric matrix, comprising: a) poly(lactide-co-glycolide) with a molecular weight between 5000 Daltons and 42,000 Daltons; b) particles of Zn.sup.+2 -complexed interferon, with a zinc-to-interferon molar ratio between 1:1 and 10:1, wherein said particles are dispersed within the poly(lactide-co-glycolide), and wherein the proportion of interferon in the controlled release composition is between 0.5 and 15 weight percent. 20. A composition for the controlled release of interferon from a polymeric matrix, comprising: a) blocked poly(lactide-co-glycolide) with a molecular weight of about 4,000-15,000 Daltons; b) particles of Zn.sup.+2 -complexed interferon, with a zinc-to-interferon molar ratio of about 2:1, wherein the Zn.sup.+2 ions are from zinc acetate wherein the weight ratio of polymer to Zn.sup.+2 -complexed interferon is about 10:1, and wherein said particles are dispersed within the polymeric matrix, and c) zinc carbonate particles dispersed in the polymeric matrix, wherein the weight ratio of zinc carbonate to Zn.sup.+2 -complexed interferon is about 1:1. 21. A controlled release composition of claim 19 wherein the particles of Zn.sup.+2 -complexed interferon also contain sodium bicarbonate. 22. A controlled release composition of claim 19 wherein the interferon is interferon-.alpha.. 23. A composition of claim 1 wherein the interferon is interferon-.alpha.. 24. A composition of claim 1 wherein the interferon is complexed with Zn.sup.+2 ions using zinc acetate. 25. A method of providing a therapeutically effective serum level of interferon in a subject for a sustained period comprising administering to the subject a dose of a composition for the controlled release of interferon from a polymeric matrix, comprising: a) a biocompatible polymer; and b) particles of metal cation-complexed interferon, wherein said particles are dispersed within the biocompatible polymer. 26. A method of claim 25 wherein the interferon is interferon-.alpha.. 27. A method of claim 25 wherein the metal cation, in the particles of metal cation-complexed interferon is selected from the group consisting of Zn.sup.+2, Ca.sup.+2, Cu.sup.+2, Mg.sup.+2 and combinations thereof. 28. A method of claim 25 wherein the interferon is complexed with Zn.sup.+2 ions using zinc acetate. 29. A method of claim 25 wherein the polymeric material is a biodegradable polymer. 30. A method of claim 29 wherein the biodegradable polymer is poly(lactide-co-glycolide). 31. A method of claim 30 wherein particles of zinc carbonate are dispersed within the poly(lactide-co-glycolide). |
