Topical oestroprogestational compositions with a systemic effect

• US 7,030,104 B2
• Filed: 09/14/2001
• Issued: 04/18/2006
• Est. Priority Date: 09/15/2000
• Status: Expired due to Fees

• Current Assignee: Laboratoire Theramex
• Original Assignee: Laboratoire Theramex
• Inventors: Thomas, Jean-Louis, Paris, Jacques, Villet, Bertrand, Gray, Georges
• Primary Examiner(s): Wang, Shengjun
• Application Number:
  US10/129,040
• Publication Number:
  US 20030181430A1
• Time in Patent Office: 1,677 Days
• Field of Search: 514/170, 514/178, 514/182, 424/485, 424/484, 424/400
• US Class Current: 514/170
• 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 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The present invention relates to the field of therapeutic chemistry and more especially to the realization of new galenic forms intended to be applied on the skin.

More particularly it relates to a topical hormonal composition with a systemic effect for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of the ovarian hormonal deficiencies in women with amenorrhea, characterized in that it comprises, as active ingredients, a progestogen derived from 19-nor progesterone and estradiol or one of its derivatives, a vehicle which allows the systemic passage of said active ingredients, chosen from the group constituted by a solubilizing agent, an absorption promoting agent, a film-forming agent, a gelling agent and their mixtures, in combination or in a mixture with suitable excipients for the realization of a gelled and/or film-forming pharmaceutical form.

Claims

1. A topical composition with a systemic effect, for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of ovarian hormonal deficiencies in women with amenorrhea, based on a progestogen and an oestrogen agent, comprising

as active ingredientss, nomegestrol and/or one of its esters or its ethers and estradiol and/or one of its esters or its ethers,

and a vehicle allowing the systemic passage of said active ingredients, selected from the group consisting of a solubilizing agent, an absorption agent, a film-forming agent, a gelling agent and their mixture,

in combination or in admixture with suitable excipients for the realization of a pharmaceutical, gelled and/or film-forming agent.

2. A topical hormonal composition with a systemic effect of claim 1, wherein the progestogen derived from 19-nor progesterone is nomegestrol acetate.

3. A topical composition with a systemic effect of claim 1, wherein the oestrogen is a fatty acid ester of estradiol.

4. A topical composition with a systemic effect of claim 1, wherein the oestrogen is an estradiol ether.

5. A topical hormonal composition with a systemic effect of claim 1, wherein the amount of nomegestrol or of one of its esters or ethers ranges from 0.05 to 5.0% by weight of the total composition.

6. A topical hormonal composition with a systemic effect of claim 5, wherein the amount of nomegestrol or of one of its esters or ethers is about 1.0% by weight of the total composition.

7. A topical hormonal composition with a systemic effect of claim 1, wherein the amount of estradiol or of one of its esters or ethers is 0.05 to 1.0% by weight of the total composition.

8. A topical hormonal composition with a systemic effect of claim 7, wherein the amount of estradiol or of one of its esters or ethers is about 0.15% by weight of the total composition.

9. A topical hormonal composition with a systemic effect of claim 1, wherein the solubilizing agent is selected from the group consisting of alcohols, water-alcohol mixtures, propyleneglycol and their mixtures.

10. A topical hormonal composition with a systemic effect of claim 1, wherein the solubilizing agent is an ethanol/water/propyleneglycol ternary mixture, in which the amount of ethanol is 30 to 60% by weight of the total composition and that of propyleneglycol is 2 to 20% by weight of the total composition.

11. A topical hormonal composition with a systemic effect of claim 1, wherein the absorption promoting agent is selected from the group consisting of dioxolanes and long chain fatty acids of 6 to 18 carbon atoms.

12. A topical hormonal composition with a systemic effect of claim 11, wherein the absorption promoting agent is 2 to 12% by weight of the total composition.

13. A topical hormonal composition with a systemic effect of claim 11, wherein the absorption promoting agent is isopropylideneglycerol or 2 n-nonyl 1,3-dioxolane.

14. A topical hormonal composition with a systemic effect of claim 1, wherein the gelling agent is selected from the group consisting of cellulose derivatives and acrylic derivatives.

15. A topical hormonal composition with a systemic effect of claim 14, wherein the acrylic derivatives is a carbomer used at a concentration of 0.3 to 1% by weight of the total composition.

16. A topical hormonal composition with a systemic effect of claim 1, wherein the film-forming agent is chosen from the group consisting of silicones, cellulose derivatives, methacrylic derivatives and polyvinylpyrrolidone derivatives.

17. A topical hormonal composition with a systemic effect of claim 16, wherein the silicone is selected from the group consisting of dimethicone, dimethiconol simethicone and their mixtures.

18. A topical hormonal composition with a systemic effect of claim 16, wherein the silicone is a mixture formed from the dimethiconol in dimethicone.

19. A topical hormonal composition with a systemic effect of claim 17, wherein the amount of silicone is 1 to 3% by weight of total composition.

20. A topical hormonal composition of claim 1, in the form of a penetrating gel, wherein it contains, in a hydroalcoholic mixture, 0.4% nomegestrol acetate, 0.15% estradiol, 8% propyleneglycol, 3% isopropylideneglycerol and 2% of a mixture formed from dimethiconol in dimethicone.

21. A topical hormonal composition of claim 1, in the form of a penetrating gel, wherein it contains, in a hydroalcoholic mixture, 0.4% nomegestrol acetate, 0.15% estradiol, 8% propyleneglycol, 3% long chain fatty acids and 2% of a mixture formed from dimethiconol in dimethicone.

22. A topical hormonal composition of claim 1, wherein it contains, in the form of a penetrating gel, in a hydroalcoholic mixture, 0.4% nomegestrol acetate, 0.15% estradiol, approximately 8% propyleneglycol and approximately 3% isopropylideneglycerol.

23. A topical hormonal composition of claim 1, in the form of a penetrating gel containing a hydroalcoholic mixture, wherein 0.4% nomegestrol acetate, 0.15% estradiol, approximately 8% propyleneglycol, and approximately 3% long chain fatty acids.

24. A topical hormonal composition of claim 3 wherein the fatty acid esters of estradiol is estradiol valerate.

25. A topical hormonal composition of claim 4 wherein the ether is promestriene.