Transdermal therapeutic system and method of use thereof for treating parkinsonism

• US 10,251,844 B2
• Filed: 10/31/2007
• Issued: 04/09/2019
• Est. Priority Date: 03/30/1998
• Status: Active Grant

• Current Assignee: LTS Lohmann Therapie-Systeme AG, Ucb Biopharma Sprl (UCB SA)
• Original Assignee: LTS Lohmann Therapie-Systeme AG, UCB Manufacturing Ireland Limited (UCB SA)
• Inventors: Muller, Walter, Peck, James V.
• Primary Examiner(s): Ghali, Isis A
• Application Number:
  US11/931,762
• Publication Number:
  US 20080138389A1
• Time in Patent Office: 4,178 Days
• Field of Search: None
• 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. A transdermal therapeutic system (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.

2. The TTS of claim 1, wherein the matrix is substantially solvent-free.

3. The TTS of claim 1, 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.

4. The TTS of claim 1, 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.

5. The TTS of claim 4, wherein the size of the TTS is 2 to 40 cm².

6. The TTS of claim 4, wherein the size of the TTS is approximately 20 cm².

7. The TTS of claim 1, 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.

8. The TTS of claim 1, wherein the matrix layer has a coat weight of approximately 50 g/m².

9. The TTS of claim 1, wherein the free base is present in the matrix layer in an amount of approximately 0.45 mg/cm².

10. The TTS of claim 1, 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.

11. The TTS of claim 1, wherein the free base is present in an amount of about 5% to 25% by weight.

12. The TTS of claim 1, wherein the free base is present in an amount of about 5% to about 15% by weight.

13. The TTS of claim 1, wherein the free base is present in an amount of approximately 9% by weight.

14. The TTS of claim 1, wherein the silicone adhesive is amine-resistant.

15. The TTS of claim 1, wherein the silicone-based adhesive system comprises BIO-PSA Q7-4301 or BIO-PSA Q7-4201.

16. The TTS of claim 10, 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.

17. The TTS of claim 10, wherein the additive comprises polyvinylpyrrolidone in an amount of about 1.5-5% by weight of the matrix.

18. The TTS of claim 17, wherein the polyvinylpyrrolidone is present in an amount of about 1.5% to 3% by weight of the matrix.

19. The TTS of claim 17, wherein the polyvinylpyrrolidone is of type 90F.