TH73258B - A liquid interferon formulation stabilized by HSA free. - Google Patents

Abstract

DC60 (23/07/47) described a stabilized, HSA-free liquid pharmaceutical mixture incorporating interferon (IFN), where the formulation was a solution containing buffers, surfactants, isotonic agents, and antioxidants. Interferon was, in fact, recombinant human IFN-beta.

Claims (33)

Revised 10/10/2018, Page 1 of 3. Claims: 1. A stabilized, HSA-free liquid pharmaceutical compound containing interferon-beta (IFN-beta), whereby the compound is a solution containing buffers, surfactants, isotonic agents, and antioxidants, whereby the antioxidant is methionine. ---------------------------------------------------------------------------------------------------- 1. A stabilized, HSA-free liquid pharmaceutical formulation containing interferon-beta (IFN-beta), where the solution comprises buffers, surfactants, isotonic agents, and antioxidants, with the antioxidant being methionine. 2. The mixture according to claim 1, whereby the interferon is IFN-beta. 3. A combination of any prior claims where IFN-beta is human IFN-beta recombinant. 4. A mixture of any preceding claims where such buffer is present in sufficient quantity to maintain the pH of such mixture within plus or minus 0.5 units of the specified pH, where the specified pH is approximately 3.0 to approximately 5.0. 5. A mixture of any prior claims where the pH is 3.5 plus or minus 0.2. 6. A mixture of any prior claims where the pH is 4.5 plus or minus 0.2. 7. A mixture of any prior claims, where such buffer is present at concentrations of approximately 5 mM to 500 mM. 8. A mixture of any prior claims, where such buffer is present at a concentration of approximately 10 mM. 9. A mixture of any prior claims where the buffer is a cetate buffer. 10. A combination of any prior claims where such isotonic agent is mannitol. 11. A mixture of any prior claims where such isotonic acid is present at concentrations of approximately 0.5 mg/ml to approximately 500 mg/ml. 12. A mixture of any prior claims where such isotonic acid is present at a concentration of approximately 55 mg/ml. 13. A combination of any prior claims where such surfactant is selectable from Pluronic R F77, Pluronic F87, Pluronic F88 and Pluronic F68. 14. A combination of any prior claims where the surfactant is Pluronic F68. 15. A mixture of any prior claims where such surfactant is present at a concentration of approximately 0.01 mg/ml to approximately 10 mg/ml. 16. A mixture of any prior claims where such surfactant is present at a concentration of approximately 1 mg/ml. 17. A combination of any prior claims where the antioxidant is methionine. 18. A mixture of any prior claims where such antioxidant is present at a concentration of approximately 0.01 to approximately 5.0 mg/ml. 19. A mixture of any prior claims where such antioxidant is present at a concentration of approximately 0.1 mg/ml. 20. A mixture of any prior claims where such interferon is present at a concentration of approximately 10 µg/ml to approximately 800 µg/ml. 21. A mixture of any prior claims where such interferon is present at a concentration of approximately 44, 88, or 264 mg/ml. 22. A mixture of any prior claims, whereby such mixture is an aqueous solution. 23. A mixture of any prior claims that also includes an antibacterial agent. 24. A mixture of any prior claims where the antibacterial agent is benzyl alcohol. 25. A mixture of any prior claims where such antibacterial agent is present at a concentration of approximately 0.1% to approximately 2.0%. 26. A mixture of any prior claims where such antibacterial agent is present at a concentration of approximately 0.2 or 0.3%. 27. Method for preparing HSA-free liquid pharmaceutical mixtures stabilized according to Patent 1-26, whereby calculated amounts of surfactants, antioxidants and isotonic agents are added to a buffer solution and then interferon (IFN) is added. 28. A hermetically sealed, sterile container suitable for storage before use, containing a liquid pharmaceutical mixture as per any of the claims from clauses 1 to 26. 29. The container of claim 28, whereby the container is a pre-filled syringe intended for single-dose dosing. 30. The container of claim 28, whereby that container is a bottle. 31. The container of claim 28, whereby such container is an automatic injection cartridge. 32. Container of claim 30 or 31, where such container is for dispensing single or multiple doses of medication. 33. A complete kit for the administration of multiple doses of any pharmaceutical mixture as per any of the claims 23 through 26, whereby the kit comprises a first container filled with any pharmaceutical mixture as per any of the claims 1 through 22 and a second cartridge filled with a solution of an antibacterial agent.