Hormone-containing transdermal therapeutic system with an active substance reservoir based on vinylacetate-vinylpyrrolidone copolymer with improved cohesion

• US 20060088580A1
• Filed: 03/12/2003
• Published: 04/27/2006
• Est. Priority Date: 03/16/2002
• Status: Abandoned Application

• Current Assignee: LTS Lohmann Therapie-Systeme AG
• Original Assignee: LTS Lohmann Therapie-Systeme AG
• Inventors: Meconi, Reinhold, Seibertz, Frank, Becker, Franz-Josef, Klein, Ursula Hildegard, Cotte, Ursula, Klein, Robert-Peter
• Application Number:
  US10/507,628
• Publication Number:
  US 20060088580A1
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

A transdermal therapeutic system in patch form for the controlled delivery of active substances to the human or animal skin comprises a backing layer, an active substance-containing reservoir attached thereto and a detachable protective layer, is characterized in that the active substance-containing reservoir contains as main components thereof at least one film former as well as at least one polymer which prevents or suppresses the crystallisation of the active substance or active substances.

Claims

1. Transdermal therapeutic system in the form of a plaster, for the controlled delivery of estrogens and/or gestagens to human or animal skin, said system having a backing layer, an active substance-containing, mono- or multilayer reservoir connected thereto, and a detachable protective layer, characterized in that the active substance-containing reservoir contains vinyl pyrrolidone-vinyl acetate copolymer and cohesion-enhancing substances, said cohesion-enhancing substances being selected from the group consisting of polyethylene, polypropylene, salts of ethylene-methacrylic acid copolymers, polystyrene, polybutene, polyisobutylene, styrene-butadiene-styrene block polymers, polyvinyl chloride, polyvinylidene chloride, polyurethane, polyamide, polysulfone, polyvinyl acetate, polyvinyl alcohol, polyethylene glycol, polyoxyethylene, polyvinyl butyral, and ethylene-vinyl acetate copolymers.

2. Transdermal therapeutic system according to claim 1, characterized in that the content of vinyl pyrrolidone-vinyl acetate copolymer in the active substance-containing reservoir is 1.0 to 95.0%-wt, preferably 2.0 to 90.0%-wt.

3. Transdermal therapeutic system according to claim 1 or 2, characterized in that the vinyl pyrrolidone/vinyl acetate ratio of the vinyl pyrrolidone-vinyl acetate copolymer is 15:

85 to 85;

15, preferably 20;

80 to 70;

30.

4. Transdermal therapeutic system according to claim 1, characterized in that the content of cohesion-improving substances in the active substance-containing reservoir is 1.0 to 60.0%-wt, preferably 2.0 to 50.0%-wt.

5. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir contains 3.0 to 70.0%-wt, preferably 5.0 to 60.0%-wt, of ethylene-vinyl acetate copolymer.

6. Transdermal therapeutic system according to claim 5, characterized in that the vinyl acetate content of the ethylene-vinyl acetate copolymer is 15 to 50%-wt, preferably 18 to 40%-wt.

7. Transdermal therapeutic system according claim 1, characterized in that the active substance-containing reservoir consists of at least two spatially separated parts.

8. Transdermal therapeutic system according to claim 7, characterized in that one spatially separated part of the active substance-containing reservoir contains an estrogen, and that the other spatially separated part contains a gestagen, either alone or in combination with an estrogen.

9. Transdermal therapeutic system according to claim 1, characterized in that the estrogen concentration in the active substance-containing reservoir is 0.5 to 10.0%-wt, preferably 1 to 5.0%-wt, and that the gestagen concentration is 0.5 to 20.0%-wt, preferably 1.0 to 10.0%-wt.

10. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir contains tack-enhancing resins in a concentration of 5.0 to 70.0%-wt, preferably 10.0 to 60.0%-wt.

11. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir contains skin permeation-enhancing substances in a concentration of 1.0 to 50.0%-wt, preferably 3.0 to 45.0%-wt.

12. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir contains emulsifiers and/or plasticizers and/or antioxidants in a respective concentration of up to 25.0%-wt, preferably 1.0 to 15.0%-wt.

13. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir contains fillers.

14. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir is made up of two or more layers.

15. Transdermal therapeutic system according to claim 14, characterized in that the individual layers of the active substance-containing reservoir contain different active substances and/or differ from each other in terms of their active substance concentration and/or their composition.

16. Transdermal therapeutic system according to claim 14 or 15, characterized in that between the layers of the active substance-containing reservoir there is interposed a flat body, preferably a membrane, a film, a textile fabric, a nonwoven fabric, or a woven fabric.

17. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir has a layer thickness of 0.02 mm to 0.5 mm, preferably 0.03 to 0.3 mm.

18. Transdermal therapeutic system according to claim 1, characterized in that the active substance-containing reservoir is provided with a pressure sensitive adhesive layer and/or a pressure-sensitive adhesive margin.

19. Process for the production of a transdermal therapeutic system according to claim 1, comprising the following steps:

preparing a solution or suspension containing the components of the active substance-containing reservoir, and

coating this solution or suspension on a flat support.

20. Process for the production of a transdermal therapeutic system according to claim 1, comprising the following steps:

preparing a melt containing the components of the active substance-containing reservoir, and

coating this melt on a flat support.

21. Use of the transdermal therapeutic system according to claim 1 for therapeutic purposes in human medicine, preferably for hormone substitution, for the prophylaxis and treatment of climacteric complaints, as well as for the prophylaxis of osteoporosis.

22. Use of the transdermal therapeutic system according to claim 1 for hormonal contraception.