Hydrogel Interferon Formulations

• US 20070248674A1
• Filed: 05/13/2005
• Published: 10/25/2007
• Est. Priority Date: 05/17/2004
• Status: Active Grant

• Current Assignee: Ares Trading SA (Merck & Co., Inc.)
• Original Assignee: Ares Trading SA (Merck & Co., Inc.)
• Inventors: Zambaldi, Ilaria, Pompili, Silvia, Esposito, Pierandrea, Del Curto, Maria
• Granted Patent: US 7,879,320 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is related to pharmaceutical Poloxamer hydrogel formulations containing an interferon. In particular, the invention relates to sustained release hydrogel formulations of interferon-beta, method of preparation and use thereof.

Claims

1-20. -20. (canceled)

21. A pharmaceutical composition comprising an interferon (IFN) and a poloxamer hydrogel.

22. The composition according to claim 21 wherein the interferon is IFN-beta.

23. The composition according to claim 22, wherein the interferon is recombinant IFN-beta.

24. The composition according claim 23, wherein the interferon is recombinant IFN-beta 1a.

25. The composition according to claim 21, wherein the composition further comprises a buffer and an anti-oxidant.

26. The composition according claim 21, wherein the composition further comprises a buffer and a surfactant.

27. The composition according to claim 21, wherein the composition further comprises a solid-gel temperature transition modifier.

28. The composition according to claim 27, wherein the solid-gel temperature transition modifier is trehalose or cyclodextrin.

29. The composition according to claim 21, wherein the poloxamer is Poloxamer 407.

30. The composition according to claim 29, wherein the composition comprises 20 to 25% w/w of Poloxamer 407.

31. The composition according to claim 21, wherein said composition is a Poloxamer 407 hydrogel comprising recombinant IFN-beta 1a, a buffer and L-methionine.

32. The composition according to claim 31, wherein the composition further comprises Poloxamer 188.

33. The composition according to claim 32, wherein the composition further comprises trehalose.

34. The composition according to claim 31, wherein the composition further comprises hydroxypropyl beta cyclodextrin.

35. The composition according to claim 21, wherein the composition is selected from the group consisting of:

a) Poloxamer 407-25% w/w

Acetate buffer 50 mM/pH 3.8-74.7% w/w

r-hIFNbeta 1a-0.012% w/w

L-Methionine-0.03% w/w

Poloxamer 188-0.24% w/w;

b) Poloxamer 407-25% w/w

Acetate buffer 50 mM/pH 3.8-72.04% w/w

r-hIFNbeta 1a-0.012% w/w

L-Methionine-0.03% w/w

Poloxamer 188-0.24% w/w

Glycerol 30°

Bé

-2.6% w/w;

c) Poloxamer 407-25% w/w

Acetate buffer 50 mM/pH 3.8-72.04% w/w

r-hIFNbeta 1a-0.012% w/w

L-Methionine-0.03% w/w

Poloxamer 188-0.24% w/w

PEG (Lutrol®

E400)-2.6% w/w;

d) Poloxamer 407-25% w/w

Acetate buffer 50 mM/pH 3.8-72.04% w/w

r-h-IFNbeta 1a-0.012% w/w

L-Methionine-0.03% w/w

Poloxamer 188-0.24% w/w

Trehalose-2.6% w/w; and

e) Poloxamer 407-20% w/w

Acetate buffer 50 mM/pH 3.8-77.34% w/w

r-h-IFNbeta 1a-0.015% w/w

L-Methionine-0.04% w/w

Hydroxypropyl-β

-Cyclodextrin-2.6% w/w.

42. A method of treating multiple sclerosis comprising the administration of a composition according to claim 21 to an individual in need of treatment.

36. A method for preparing an IFN hydrogel composition comprising adding a calculated amount of poloxamer to a buffered solution at a temperature wherein a homogeneous polymer solution is formed and then adding an interferon.

37. The method according to claim 36, wherein the buffer solution contains a solution-to-gel temperature transition modifier.

38. The method according to claim 36, wherein the buffer solution contains a solution-to-gel temperature transition modifier selected from trehalose and cyclodextrin.

39. The method according to claim 36, wherein the interferon is added from an interferon solution comprising interferon and stabilizers selected from L-methionine, poloxamer 188 or a combination thereof.

40. The method according to claim 37, wherein the interferon is added from an interferon solution comprising interferon and stabilizers selected from L-methionine, poloxamer 188 or a combination thereof.

41. The method according to claim 38, wherein the interferon is added from an interferon solution comprising interferon and stabilizers selected from L-methionine, poloxamer 188 or a combination thereof.