TRANSDERMAL THERAPEUTIC SYSTEM FOR ADMINISTERING THE ACTIVE SUBSTANCE BUPRENORPHINE

• US 20100119585A1
• Filed: 11/07/2007
• Published: 05/13/2010
• Est. Priority Date: 11/21/2006
• Status: Active Grant

• Current Assignee: LTS Lohmann Therapie-Systeme AG
• Original Assignee: LTS Lohmann Therapie-Systeme AG
• Inventors: Horstmann, Michael, Mueller, Walter, Hille, Thomas
• Granted Patent: US 9,308,202 B2
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• 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: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention relates to a transdermal therapeutic system for administering the active substance buprenorphine. Said system comprises at least one carboxylic acid that determines the solubility of buprenorphine in the matrix layer and that can likewise be absorbed. The transdermal therapeutic system according to the invention is used in the treatment of pain and is characterized by a considerably increased utilization of the active substance.

Claims

1. Transdermal therapeutic system for administering buprenorphine to the skin, comprising an active-ingredient-impermeable backing layer, at least one pressure-sensitive adhesive matrix layer comprising the active ingredient buprenorphine and at least one carboxylic acid, and, if desired, a protective layer to be detached before use, characterized in that the matrix layer is constructed on the basis of polysiloxanes or polyisobutylene, the buprenorphine is in solution in the carboxylic acid or carboxylic acids, and this solution is in dispersion in the form of droplets in the matrix layer.

2. Transdermal therapeutic system according to claim 1, characterized in that the polysiloxane is an amine-resistant dimethylpolysiloxane.

3. Transdermal therapeutic system according to claim 1, characterized in that the polysiloxane is a mixture of an amine-resistant and a non-amine-resistant dimethylpolysiloxane, in which the non-amine-resistant dimethylpolysiloxane is present at up to 40% by weight.

4. Transdermal therapeutic system according to claim 1, characterized in that the carboxylic acid diffuses into the skin more quickly than does the active ingredient buprenorphine.

5. Transdermal therapeutic system according to claim 1, characterized in that the amount of the dispersed solution is up to 40% by weight, preferably up to 20% by weight.

6. Transdermal therapeutic system according to claim 1, characterized in that the carboxylic acid is liquid at skin temperature.

7. Transdermal therapeutic system according to claim 6, characterized in that the carboxylic acid is selected from the group consisting of oleic acid, laevulinic acid, linoleic acid and linolenic acid.

8. Transdermal therapeutic system according to claim 6, characterized in that buprenorphine and laevulinic acid are present in the same weight ratio.

9. Transdermal therapeutic system according to claim 1, characterized in that the matrix layer is in diffusible contact with a layer based on polyacrylates.

10. Transdermal therapeutic system according to claim 9, characterized in that the polyacrylate layer is embodied as a self-adhesive skin contact layer.

11. Transdermal therapeutic system according to claim 10, characterized in that the polyacrylate adhesive possesses no free carboxyl groups.

12. Transdermal therapeutic system according to claim 1, characterized in that active substance utilization under in vivo conditions of at least 30% is achieved.

13. A method of treating pain which comprises administering to a patient in need thereof a therapeutically effective amount of the transdermal therapeutic system of claim 1.

14. Transdermal therapeutic system according to claim 2, characterized in that the polysiloxane is a mixture of an amine-resistant and a non-amine-resistant dimethylpolysiloxane, in which the non-amine-resistant dimethylpolysiloxane is present at up to 40% by weight;

the carboxylic acid diffuses into the skin more quickly than does the active ingredient buprenorphine and is liquid at skin temperature; and

the amount of the dispersed solution is up to 40% by weight.

15. Transdermal therapeutic system according to claim 14, characterized in that active substance utilization under in vivo conditions of at least 40%.

16. Transdermal therapeutic system according to claim 15, characterized in that active substance utilization under in vivo conditions of at least 50%.