Gestodene-containing agent for transdermal administration

• US 5,788,984 A
• Filed: 03/13/1995
• Issued: 08/04/1998
• Est. Priority Date: 10/27/1988
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Tack, Johannes Wilhelm, Taeuber, Ulrich, Guenther, Clemens, Schmidt-Gollwitzer, Karin, Riedl, Jutta
• Primary Examiner(s): Clardy, S. Mark
• Assistant Examiner(s): Harrison, Robert H.
• Application Number:
  US08/403,137
• Time in Patent Office: 1,240 Days
• Field of Search: 424/400, 424/447, 424/448, 424/449
• US Class Current: 424/449
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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: 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 15/12 for climacteric disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

An agent for transdermal administration contains gestodene, optionally in combination with one or more estrogen(s).

Claims

1. A pharmaceutical composition for transdermal administration comprising:

gestodene and a pharmaceutically acceptable carrier for transdermal administration, and, optionally, an estrogenic compound,

wherein the amount of gestodene dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. % and the amount of said estrogenic compound, if present dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. %.

2. A composition of claim 1, which is an ointment, lotion or spray.

3. A composition of claim 1, comprising no estrogenic compound.

4. A composition of claim 1 comprising an estrogenic compound.

5. A composition of claim 4, wherein the estrogen is estradiol, estriol, 17-ethynylestradiol, or an ester of these compounds.

6. A composition of claim 4, comprising 1 or 2 estrogenic compounds.

7. A composition according to claim 4, wherein the weight ratio of gestodene to estrogenic compound is 5:

1-1;

10.

8. A composition according to claim 1, wherein said pharmaceutically acceptable carrier comprises at least one penetration-enhancing agent wherein said agent is

1,2-propanediol,

benzyl alcohol,

a saturated or unsaturated fatty alcohol having 8-18 C atoms,

mineral oil,

a saturated or unsaturated fatty acid of 8-18 C atoms,

a fatty acid ester of the formula C₃ --(CH₂)_n --COOR wherein n is 8-18 and R is alkyl having up to 6 C atoms,

a dicarboxylic acid diester of the formula R'"'"'OCO(CH₂)_m COOR'"'"' wherein m is 4-8 and R'"'"' is, in each case independently, alkyl of up to 6 C atoms, or combinations thereof.

9. An article for transdermal administration comprising:

a pharmaceutical composition comprising gestodene and a pharmaceutically acceptable carrier for transdermal administration, and, optionally, an estrogenic compound;

wherein the amount of gestodene dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. % and the amount of said estrogenic compound, if present, dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. %; and

a transdermal therapeutic system wherein said composition is in said transdermal therapeutic system.

10. An article according to claim 9, comprising an estrogenic compound.

11. An article of claim 10 wherein said composition contains an estrogenic compound which is estradiol, an ester of estradiol, estriol, an ester of estriol, 17-ethynylestradiol or an ester of 17-ethynylestradiol.

12. An article of claim 9, wherein the transdermal therapeutic system comprises:

(a) an impermeable cover layer,

a medicinal layer adhering to the cover layer and permeable to these components, and containing the gestodene and optionally an estrogen, and, optionally, penetration-enhancing media, this medicinal layer being pressure-sensitive, skin adhesive or being covered or surrounded by a skin adhesive, wherein this skin adhesive optionally contains penetration-enhancing media, and

a protective layer that can be pulled off, or

(b) an impermeable cover layer,

a medicinal reservoir located on or in the cover layer and containing gestodene, optionally an estrogen and, optionally, penetration-enhancing media,

a polymer layer permeable to these components,

a layer of skin adhesive which is permeable and optionally contains penetration-enhancing media, and

a protective layer that can be pulled off.

13. An article according to claim 9, comprising no estrogenic compound.

14. An article according to claim 10, comprising 1-2 estrogenic compounds.

15. An article according to claim 10, wherein the weight ratio of gestodene to estrogenic compound is 5:

1-1;

10.

16. An article according to claim 9, wherein said pharmaceutically acceptable carrier comprises at least one penetration-enhancing agent wherein said agent is

1,2-propanediol,

benzyl alcohol,

a saturated or unsaturated fatty alcohol having 8-18 C atoms,

mineral oil,

a saturated or unsaturated fatty acid of 8-18 C atoms,

a fatty acid ester of the formula C₃ --(CH₂)_n --COOR wherein n is 8-18 and R is alkyl having up to 6 C atoms,

a dicarboxylic acid diester of the formula R'"'"'OCO(CH₂)_m COOR'"'"' wherein m is 4-8 and R'"'"' is, in each case independently, alkyl of up to 6 C atoms, or

combinations thereof.

17. An article according to claim 9, wherein the amount of gestogen is 0.8-5 mg.

18. In a method of administering gestodene to a patient, the improvement comprising administering gestodene transdermally, optionally in combination with an estrogenic compound,

wherein said gestodene and optional estrogenic compound are dissolved or suspended in a pharmaceutically acceptable carrier, and

wherein the amount of gestodene dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. % and the amount of said estrogenic compound, if present, dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. %.

19. A method of claim 18, wherein gestodene is administered in the form of an ointment, lotion or spray.

20. A method of claim 18, wherein no estrogenic compound is administered.

21. A method of claim 18, wherein an estrogenic compound is administered.

22. A method of claim 21, wherein 1 or 2 estrogenic compounds are administered.

23. A method of claim 21, wherein the estrogen is estradiol, estriol, 17-ethynylestradiol, or an ester of these compounds.

24. A method of claim 18 for treating endometriosis, a gestagen-dependent tumor, or premenstrual syndrome.

25. A method of claim 18 for treating climacteric symptoms, for prevention of osteoporosis, for cycle regulation or for cycle stabilization.

26. A method of claim 25 comprising also administering an estrogenic compound.

27. A method according to claim 21, wherein the weight ratio of gestodene to estrogenic compound is 5:

1-1;

10.

28. A method according to claim 18, wherein said pharmaceutically acceptable carrier comprises at least one penetration-enhancing agent wherein said agent is

1,2-propanediol,

benzyl alcohol,

a saturated or unsaturated fatty alcohol having 8-18 C atoms,

mineral oil,

a saturated or unsaturated fatty acid of 8-18 C atoms,

a fatty acid ester of the formula C₃ --(CH₂)_n --COOR wherein n is 8-18 and R is alkyl having up to 6 C atoms,

a dicarboxylic acid diester of the formula R'"'"'OCO(CH₂)_m COOR'"'"' wherein m is 4-8 and R'"'"' is, in each case independently, alkyl of up to 6 C atoms, or

combinations thereof.

29. A method according to claim 18, wherein the amount of gestogen is 0.8-5 mg.

30. In a method of administering gestodene to a patient, the improvement comprising administering gestodene, optionally in combination with an estrogenic compound, by a transdermal therapeutic system,

wherein said gestodene and optional estrogenic compound are dissolved or suspended in a pharmaceutically acceptable carrier, and

wherein the amount of gestodene dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. % and the amount of said estrogenic compound, if present, dissolved or suspended in said pharmaceutically acceptable carrier is 0.01-25 wt. %.

31. A method of claim 30, wherein said estrogenic compound is estradiol, an ester of estradiol, estriol, an ester of estriol, 17-ethynylestradiol or an ester of 17-ethynyl-estradiol.

32. A method of claim 30, wherein the transdermal therapeutic system comprises:

(a) an impermeable cover layer,

a medicinal layer adhering to the cover layer and permeable to these components, and containing the gestodene and optionally an estrogen, and, optionally, penetration-enhancing media, this medicinal layer being pressure-sensitive, skin adhesive or being covered or surrounded by a skin adhesive, wherein this skin adhesive optionally contains penetration-enhancing media, and

a protective layer that can be pulled off, or

(b) an impermeable cover layer,

a medicinal reservoir located on or in the cover layer and containing gestodene, optionally an estrogen and, optionally, penetration-enhancing media,

a polymer layer permeable to these components,

a layer of skin adhesive which is permeable and optionally contains penetration-enhancing media, and

a protective layer that can be pulled off.

33. A method according to claim 30, wherein no estrogenic compound is administered.

34. A method according to claim 30, wherein an estrogenic compound is administered.

35. A method according to claim 34, wherein the weight ratio of gestodene to estrogenic compound is 5:

1-1;

10.

36. A method according to claim 30, wherein said pharmaceutically acceptable carrier comprises at least one penetration-enhancing agent wherein said agent is

1,2-propanediol,

benzyl alcohol,

a saturated or unsaturated fatty alcohol having 8-18 C atoms,

mineral oil,

a saturated or unsaturated fatty acid of 8-18 C atoms,

a fatty acid ester of the formula C₃ --(CH₂)_n --COOR wherein n is 8-18 and R is alkyl having up to 6 C atoms,

a dicarboxylic acid diester of the formula R'"'"'OCO(CH₂)_m COOR'"'"' wherein m is 4-8 and R'"'"' is, in each case independently, alkyl of up to 6 C atoms, or

combinations thereof.

37. A method according to claim 30, wherein the amount of gestogen is 0.8-5 mg.

38. A method according to claim 30, wherein the delivery rate of gestodene is 0.02-0.04 μ

g/cm² /h.