Agent for transdermal administration that contains gestodene esters

• US 5,858,394 A
• Filed: 05/21/1996
• Issued: 01/12/1999
• Est. Priority Date: 08/26/1993
• Status: Expired due to Fees

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Tauber, Ulrich, Lipp, Ralph, Esperling, Peter, Laurent, Henry, Gunther, Clemens, Riedl, Jutta
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HOWARD, SHARON LEE
• Application Number:
  US08/602,808
• Time in Patent Office: 966 Days
• Field of Search: 424/448, 424/449, 514/946
• 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: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

An agent for transdermal administration is described, which is characterized in that it contains gestodene esters with 1 to 20 carbon atoms in the ester radical optionally in combination with one or two estrogen(s).

Claims

1. A transdermal therapeutic system (TTS), comprising one to three gestodene ester compounds with 1 to 20 carbon atoms in the ester radical, optionally in combination with a gestodene compound and/or with one to three estrogen compound(s), and further comprising:

a)

(i) an impermeable cover layer,

(ii) one to three acrylate matrix layer(s) adhering to said cover layer and comprising said compounds and, optionally, penetration-enhancing agents, wherein said matrix layer(s) are permeable to said compounds and optional penetration-enhancing agents and are self-adhering to skin, or wherein said matrix layer(s) are covered or surrounded by a skin contact adhesive that optionally contains penetration-enhancing agents, and

(iii) a removable protective layer which covers said matrix layer, or

b)

(i) a cover provided with a contact adhesive that optionally contains penetration-enhancing agents,

(ii) one to three acrylate matrix layer(s), each of which is attached to an impermeable cover, which in turn is attached to said contact adhesive, leaving uncovered a contact adhesive border, wherein said matrix layer(s) contain said compounds and, optionally, penetration-enhancing agents, and

(iii) a removable protective layer which covers said matrix layer, or

c)

(i) an impermeable cover layer,

(ii) one to three pharmaceutical agent reservoir(s) that are present on or in the cover layer and that contain said compounds and, optionally, penetration-enhancing agents,

(iii) one to three acrylate polymer layer(s) that are in contact with and are permeable to said compounds and penetration-enhancing agents,

(iv) a permeable skin contact adhesive layer that is in contact with the polymer layer(s) and optionally contains penetration-enhancing agents, and

(v) a removable protective layer which covers said polymer layer.

2. A TTS according to claim 1, wherein said gestodene esters have 2 to 12 carbon atoms in the ester radical.

3. A TTS according to claim 1, wherein said gestodene esters are alkanoates with 2 to 8 carbon atoms in the alkanoyl radical.

4. A TTS according to claim 1, wherein said estrogens are 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 esters of these compounds.

5. A TTS according to claim 1, further comprising an active ingredient-containing matrix layer or a pharmaceutical agent reservoir.

6. A TTS according to claim 1, which contains two or three active ingredient-containing matrix layers or pharmaceutical agent reservoirs.

7. A TTS according to claim 6, wherein the active ingredient-containing matrix layers or the pharmaceutical agent reservoirs contain different active ingredients.

8. A method for the transdermal administration of an active ingredient or active ingredient mixture, comprising placing on the skin of a subject a TTS of claim 1.

9. The method of claim 8, wherein the estrogen(s) are 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 esters of these estrogens.

11. A method for the treatment of menopausal symptoms, for the prevention of osteoporosis, for cycle regulation, for cycle stabilization or for transdermal contraception, comprising placing on the skin of a subject a TTS of claim 1.

12. A TTS of claim 3, wherein said gestodene alkanoates have 3, 5 or 6 carbon atoms in the alkanoyl radical.

13. A TTS of claim 12, wherein said gestodene alkanoate is gestodene propionate.

14. A TTS of claim 12, wherein said gestodene alkanoate is gestodene valerate.

15. A TTS of claim 12, wherein said gestodene alkanoate is gestodene capronate.

10. A method for transdermal contraception, for the treatment of endometriosis, for the treatment of gestagen-dependent tumors or for the treatment of premenstrual syndrome, comprising placing on the skin of a subject a TTS which comprises one to three acrylate matrix layers and one to three gestodene esters with 1 to 20 carbon atoms in the ester radical, optionally in combination with gestodene, but which does not contain estrogen.