Patent EA-001792-B1 (EA)
Title: Composition comprising il-1 inhibitor and hydrogel ester and methods administering thereof
Inventor: COLLINS DAVID S
IPC: A61K38/20
Filed: 1997-02-10
Abstract: 1. A pharmaceutical composition comprising a controlled release hydrogel ester and a proteinaceous interleukin-l inhibitor (IL-1). 2. The composition of Claim 1, wherein the hydrogel ester controlled release polymer is hyaluronan or a salt thereof. 3. The composition of claim 2, wherein the hyaluronan is hyaluronic acid. 4. The composition of claim 2, wherein the hyaluronan is hylan. 5. The composition of claim 2, wherein the hyaluronan is sodium hyaluronate. 6. The composition of claims 2 to 5, wherein the hyaluronan is present in a range of 0.1-5% w/v. 7. The composition of claim 1, wherein the hydrogel ester is poly(vinylpyrrolidone). 8. The composition of claim 1, wherein the hydrogel ester is cellulose. 9. The composition of claim 8, wherein the cellulose is carboxymethylcellulose.  10. The composition of claims 1 to 9, wherein said proteinaceous interleukin-1 inhibitor is an IL-1 receptor antagonist (IL-1ra). 11. The composition of claim 10, wherein said IL-1ra comprises amino acid sequence, which, at least, by 70% is homologous SEQ ID N 2. 12. The composition of claim 10, wherein said IL-1ra comprises amino acid sequence, which, at least, by 80% is homologous SEQ ID N 2. 13. The composition of claim 10, wherein said IL-1ra comprises amino acid sequence, which, at least, by 90% is homologous SEQ ID N 2. 14. The composition of claim 10, wherein said IL-1ra comprises amino acid sequence, which, at least, by 95% is homologous SEQ ID N 2. 15. The composition of claim 10, wherein said IL-1ra comprises amino acid SEQ ID N 2 or its deleted biologically-active variant. 16. The composition of claim 15, wherein said IL-1ra comprises SEQ ID N 2 with N- or C- terminal deletion. 17. The composition of claim 15, wherein said IL-1ra comprises amino acid SEQ ID N 2. 18. The composition of claim 15, wherein said IL-1ra is non-glycosylated. 19. The composition of claims 15, wherein said IL-1ra is methionyl IL-1ra. 20. The composition of claims 10 to 17, wherein said IL-1ra is glycosylated. 21. The composition of claims 10 to 20, wherein said IL-1ra is produced by recombinant DNA methods. 22. The composition of claims 10 to 21, wherein said IL-1ra is fused on the crboxy-terminal region with a partial or full-sized constant domein of heavy or light chain of human's immunoglobuline. 23. The composition of claims 10 to 22, wherein said IL-1ra is conjugated with dextane. 24. The composition of claims 10 to 23, wherein the IL-1ra concentration is present in a range of 0.1-200 mg/ml. 25. The composition of claims 2 to 24, wherein the hyaluronan concentration is present in a range of 0.1-5% w/v. 26. The composition of claims 2 to 25, wherein the hyaluronan is present in a concentration of about 2% w/v and the IL-1ra is present in a concentration of about 100 mg/ml. 27. A method for treating a patient afflicted with an IL-1 mediated disease, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claims 1 to 26. 28. The method for treating a patient afficted with inflammatory diseases of joints, disseminated sclerosis, leucaemia, from ischemic and reperfusion trauma, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claims 1 to 26. 29. The method of claim 27, wherein said disease is an inflammatory disease of a joint selected from the group consisting of rheumatoid arthritis, osteo arthritis and other inflammatory conditions resulting from strain, sprain, trauma, infection, cartilage damage or orthopedic surgery. 30. The method of claims 27 to 29, wherein the composition is administered by intravenous, intramuscular, intraarticular or subcutaneous administration. 31. The method of claims 27 to 29, wherein the composition is administered prior to, during or after administering anti-inflammoatory medicaments. 32. The method of claim 31, wherein said anti-inflammoatory medicament is selected from non-steriods, NSAIDs anti-inflammatory preparation, corticosteroids, low-active anti-reumatic preparations (SAARDs) or preparations modifying a disease. 33. Use of a pharmaceutical composition of claims 1 to 26 in the preparation of a medicament for treating IL-1 mediated disease. 34. Use of a pharmaceutical composition of claims 1 to 26 in the preparation of a medicament for treating inflammatory diseases of joints, disseminated sclerosis, leucaemia, ischemic and reperfusion trauma. 35. Use of a pharmaceutical composition of claim 34, wherein an inflammatory disease comprises rheumatoid arthritis, osteo arthritis and other inflammatory conditions resulting from strain, sprain, trauma, infection, cartilage damage or orthopedic surgery. 36. Use of a pharmaceutical composition of claims 33 to 35, wherein said pharmaceutical composition is administered by intravenous, intramuscular, intraarticular or subcutaneous administration. 37. Use of a pharmaceutical composition of claims 33 to 36, wherein said composition is administered prior to, during or after administering anti-inflammoatory medicaments. 38. Use of a pharmaceutical composition of claim 37, wherein said anti-inflammoatory medicament is selected from non-steriods, NSAIDs anti-inflammatory preparation, corticosteroids, low-active anti-reumatic preparations (SAARDs) or preparations modifying a disease.