Transdermal therapeutic systems that contain sex steroids and dimethyl isosorbide

• US 5,904,931 A
• Filed: 11/08/1996
• Issued: 05/18/1999
• Est. Priority Date: 02/18/1994
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Lipp, Ralph, Gunther, Clemens, Riedl, Jutta, Tauber, Ulrich
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/693,050
• Time in Patent Office: 921 Days
• Field of Search: 424/447, 424/448, 424/449
• 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 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 9/7061 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: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

Transdermal therapeutic systems that contain sex steroids and optionally penetration-enhancers and crystallization inhibitors are described, which are characterized in that they contain dimethyl isosorbide, with the exception of systems that contain active ingredient-containing, non-free-flowing gel phases or 3-keto-desogestrel.

Claims

1. A transdermal therapeutic system comprising

at least one matrix layer having an active ingredient phase comprising one or more sex steroids and, in an amount of 1 to 40% by weight relative to the entire active ingredient phase, dimethyl isosorbide, and

a skin contact adhesive,

provided that 3-keto-desogestrel is not one of the sex steroids and provided that the system does not contain an active ingredient-containing, non-free-flowing gel phase.

2. The system of claim 1 wherein the one or more sex steroids include a gestagen, an estrogen or a combination thereof.

3. The system of claim 1 wherein the one or more sex steroids include gestodene, levonorgestrel, desogestrel, norethisterone or norethisterone acetate.

4. The system of claim 1 wherein the one or more sex steroids include estradiol, estriol, 17α

-ethinylestradiol, mestranol, 14α

,17α

-ethanoestra-1,3,5(10)-triene-3,17β

-diol, 14α

,17α

-ethanoestra-1,3,5(10)-triene-3,16α

,17β

-triol or an ester of one of these compounds.

5. The system of claim 1 wherein the one or more sex steroids include a gestagen and an estrogen.

6. The system of claim 1 wherein the one or more sex steroids include levonorgestrel.

7. The system of claim 1 wherein the one or more sex steroids include a gestagen and an estrogen in a concentration ratio of gestagen to estrogen of from 5:

1 to 1;

5.

8. The system of claim 1 additionally comprising a penetration enhancer.

9. The system of claim 1 additionally comprising a crystallization inhibitor.

10. The system of claim 1 wherein dimethyl isosorbide is provided in an amount of 5 to 25% by weight relative to the entire active ingredient phase.

11. The system of claim 1 which comprises:

an impermeable cover layer;

one to three matrix layer(s) containing the one or more sex steroids and dimethyl isosorbide adhered to the cover layer;

a skin contact adhesive, optionally containing a penetration-enhancing agent, covering the matrix layer(s); and

a removable protective layer over the skin contact adhesive.

12. The system of claim 1 which comprises:

a cover having a contact adhesive and optionally a penetration-enhancing agent;

one or two matrix layer(s) containing the one or more sex steroids and dimethyl isosorbide adhered to the cover layer such that they leave an adhesive border from the cover uncovered; and

a removable protective layer.

13. The system of claim 11, which has only one matrix layer containing the one or more sex steroids.

14. The system of claim 11, which has two or three matrix layers each containing the one or more sex steroids.

15. The system of claim 11, which has a matrix layer containing a mixture of two or more different sex steroids.

16. The system of claim 12, which has only one matrix layer containing the one or more sex steroids.

17. The system of claim 12, which has two matrix layers each containing the one or more sex steroids.

18. The system of claim 12, which has a matrix layer containing a mixture of two or more different sex steroids.

19. A method for contraception, treatment of endometriosis, treatment of gestagen-dependent tumors or treatment of premenstrual syndrome which comprises administering a sex steroid transdermally by a system according to claim 1, wherein the one or more sex steroids do not include an estrogen.

20. A method for treatment of menopausal symptoms, prevention of osteoporosis, regulation or stabilization of the menstrual cycle or contraception which comprises administering a sex steroid transdermally by a system according to claim 1.