TRANSDERMAL THERAPEUTIC SYSTEM FOR TREATING PARKINSONISM

• US 20080138389A1
• Filed: 10/31/2007
• Published: 06/12/2008
• Est. Priority Date: 03/30/1998
• Status: Active Grant

• Current Assignee: LTS Lohmann Therapie-Systeme AG, Ucb Biopharma Sprl (UCB SA)
• Original Assignee: Ucb Biopharma Sprl (UCB SA)
• Inventors: Peck, James V., Muller, Walter
• Granted Patent: US 10,251,844 B2
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7038 Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61K 9/7092 Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A substantially solvent-free matrix layer containing (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol is produced by adding an active substance to an adhesive solution, coating the resultant active substance-containing adhesive solution onto a suitable sheet, and removing the solvents in a drying process to give said substantially solvent-free matrix layer.

Claims

1-16. -16. (canceled)

17. A self-adhesive matrix comprising an acrylate-based or silicone-based polymer adhesive system having distributed therein (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base in an amount of about 5% to 40% by weight of the matrix.

18. The matrix of claim 17, said matrix being substantially solvent-free.

19. The matrix of claim 17, wherein the adhesive system is acrylate-based, comprising a polymer containing at least two types of monomer selected from the group consisting of acrylic acid, acrylamide, hexylacrylate, 2-ethylhexylacrylate, hydroxyethylacrylate, octylacrylate, butylacrylate, methyl-acrylate, glycidylacrylate, methacrylic acid, methacrylamide, hexylmethacrylate, 2-ethylhexylmethacrylate, octylmethacrylate, methylmethacrylate, glycidyl-methacrylate, vinylacetate and vinylpyrrolidone, at least one of said types being an acrylic or methacrylic acid derivative.

20. The matrix of claim 17, wherein the adhesive system is silicone-based, comprising (a) an amine-resistant polydimethylsiloxane adhesive wherein methyl groups are optionally replaced by ethyl or phenyl groups, and (b) an additive having increased solubility for the free base, in an amount effective to increase dissolving capacity of the matrix for the free base.

21. The matrix of claim 20, wherein the free base is present in an amount of about 5% to 25% by weight.

22. The matrix of claim 20, wherein the free base is present in an amount of about 5% to about 15% by weight.

23. The matrix of claim 20, wherein the free base is present in an amount of approximately 9% by weight.

24. The matrix of claim 20, wherein the silicone adhesive is amine-resistant.

25. The matrix of claim 20, wherein the silicone-based adhesive system comprises BIO-PSA Q7-4301 or BIO-PSA Q7-4201.

26. The matrix of claim 20, wherein the additive comprises polyvinylpyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate, polyethylene glycol, polypropylene glycol, glycerol, a fatty acid ester of glycerol and/or a copolymer of ethylene and vinyl acetate.

27. The matrix of claim 20, wherein the additive comprises polyvinylpyrrolidone in an amount of about 1.5-5% by weight of the matrix.

28. The matrix of claim 27, wherein the polyvinylpyrrolidone is present in an amount of about 1.5% to 3% by weight of the matrix.

29. The matrix of claim 27, wherein the polyvinylpyrrolidone is of type 90F.

30. A transdermal therapeutic system (TTS) comprising (a) a self-adhesive matrix that comprises an acrylate-based or silicone-based polymer adhesive system having distributed therein (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base in an amount of about 5% to 40% by weight of the matrix, (b) a backing layer inert to the components of the matrix, and (c) a protective layer that is removable prior to use.

31. The TTS of claim 30, wherein the matrix is substantially solvent-free.

32. The TTS of claim 30, wherein the adhesive system is acrylate-based, comprising a polymer containing at least two types of monomer selected from the group consisting of acrylic acid, acrylamide, hexylacrylate, 2-ethylhexylacrylate, hydroxyethylacrylate, octylacrylate, butylacrylate, methyl-acrylate, glycidylacrylate, methacrylic acid, methacrylamide, hexylmethacrylate, 2-ethylhexylmethacrylate, octylmethacrylate, methylmethacrylate, glycidyl-methacrylate, vinylacetate and vinylpyrrolidone, at least one of said types being an acrylic or methacrylic acid derivative.

33. The TTS of claim 30, said TTS being of sufficient size, when applied to skin of a subject, to administer a daily dose of the free base and to achieve thereby a therapeutic level of the free base.

34. The TTS of claim 33, wherein the size of the TTS is 2 to 40 cm².

35. The TTS of claim 33, wherein the size of the TTS is approximately 20 cm².

36. The TTS of claim 30, wherein the free base is present in the matrix in an amount that makes available for transdermal delivery a 1-10 mg dose of the free base.

37. The TTS of claim 30, wherein the matrix layer has a coat weight of approximately 50 g/m².

38. The TTS of claim 30, wherein the free base is present in the matrix layer in an amount of approximately 0.45 mg/cm².

39. A method for treating Parkinson'"'"'s syndrome in a subject, comprising administering to the subject a TTS comprising a self-adhesive matrix that comprises an acrylate-based or silicone-based polymer adhesive system having distributed therein (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base in an amount of about 5% to 40% by weight of the matrix.

40. The method of claim 39, wherein the matrix of the TTS is substantially solvent-free.

41. The method of claim 39, wherein the adhesive system of the TTS matrix is acrylate-based, comprising a polymer containing at least two types of monomer selected from the group consisting of acrylic acid, acrylamide, hexylacrylate, 2-ethylhexylacrylate, hydroxyethylacrylate, octylacrylate, butylacrylate, methyl-acrylate, glycidylacrylate, methacrylic acid, methacrylamide, hexylmethacrylate, 2-ethylhexylmethacrylate, octylmethacrylate, methylmethacrylate, glycidyl-methacrylate, vinylacetate and vinylpyrrolidone, at least one of said types being an acrylic or methacrylic acid derivative.

42. The method of claim 39, wherein the adhesive system of the TTS matrix is silicone-based, comprising (a) an amine-resistant polydimethylsiloxane adhesive wherein methyl groups are optionally replaced by ethyl or phenyl groups, and (b) an additive having increased solubility for the free base, in an amount effective to increase dissolving capacity of the matrix for the free base.

43. The method of claim 42, wherein the free base is present in the TTS matrix in an amount of about 5% to 25% by weight of the matrix.

44. The method of claim 42, wherein the free base is present in the TTS matrix in an amount of about 5% to about 15% by weight of the matrix.

45. The method of claim 42, wherein the free base is present in the TTS matrix in an amount of approximately 9% by weight of the matrix.

46. The method of claim 42, wherein the silicone adhesive in the TTS matrix is amine-resistant.

47. The method of claim 42, wherein the silicone-based adhesive system of the TTS matrix comprises BIO-PSA Q7-4301 or BIO-PSA Q7-4201.

48. The method of claim 42, wherein the additive in the adhesive system of the TTS matrix comprises polyvinylpyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate, polyethylene glycol, polypropylene glycol, glycerol, a fatty acid ester of glycerol and/or a copolymer of ethylene and vinyl acetate.

49. The method of claim 42, wherein the additive in the adhesive system of the TTS matrix comprises polyvinylpyrrolidone in an amount of about 1.5-5% by weight of the matrix.

50. The method of claim 49, wherein the polyvinylpyrrolidone is present in an amount of about 1.5% to 3% by weight of the matrix.

51. The method of claim 49, wherein the polyvinylpyrrolidone is of type 90F.

52. The method of claim 39, wherein the TTS is of sufficient size, when applied to skin of the subject, to administer a daily dose of the free base and to achieve thereby a therapeutic level of the free base.

53. The method of claim 52, wherein the size of the TTS is 2 to 40 cm².

54. The method of claim 52, wherein the size of the TTS is approximately 20 cm².

55. The method of claim 39, wherein the free base is present in the TTS matrix in an amount that makes available for transdermal delivery a 1-10 mg dose of the free base.

56. The method of claim 39, wherein the TTS matrix layer has a coat weight of approximately 50 g/m².

57. The method of claim 39, wherein the free base is present in the TTS matrix layer in an amount of approximately 0.45 mg/cm².

58. The method of claim 39, wherein the TTS is administered daily to the subject.

59. A method for treating Parkinson'"'"'s syndrome in a subject, comprising administering to the subject a TTS comprising (a) a self-adhesive matrix layer of coat weight approximately 50 g/m², that comprises a silicone-based polymer adhesive system having distributed therein (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base in an amount of approximately 9% by weight of the matrix layer;

said adhesive system comprising an amino-resistant silicone adhesive and polyvinylpyrrolidone in an amount of about 1.5-5% by weight of the matrix;

(b) a backing layer inert to the components of the matrix layer; and

(c) a protective layer that is removable prior to use;

the TTS being in a form of a 2 to 40 cm² patch or plaster.