Pharmaceutical composition for transdermal or transmucosal administration comprising at least one progestin and/or at least one oestrogen, process for preparing it and uses thereof

• US 20040110732A1
• Filed: 03/20/2003
• Published: 06/10/2004
• Est. Priority Date: 12/10/2002
• Status: Abandoned Application

• Current Assignee: Besins International Belgique
• Original Assignee: Besins International Belgique
• Inventors: Masini-Eteve, Valerie, Taravella, Brigitte
• Application Number:
  US10/393,077
• Publication Number:
  US 20040110732A1
• Time in Patent Office: Days
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives

Abstract

The present invention relates to a novel pharmaceutical composition for transdermal or transmucosal administration, comprising

at least one progestin, and/or

at least one oestrogen,

at least one percutaneous absorption promoter which is a hydroxy acid or a pharmaceutically acceptable salt of a hydroxy acid.

Claims

1. Pharmaceutical composition for transdermal or transmucosal administration, comprising

at least one progestin, and/or

at least one oestrogen,

at least one percutaneous absorption promoter which is a hydroxy acid or a pharmaceutically acceptable salt of a hydroxy acid.

2. Pharmaceutical composition according to claim 1, in which the hydroxy acid is an α

-hydroxy acid preferably selected from the group consisting of lactic acid, glycolic acid, malic acid, citric acid, isocitric acid, mandelic acid, benzylic acid, glyceric acid, tartronic acid, α

-hydroxybutyric acid, α

-hydroxyoctanoic acid, pyruvic acid, ethylglycolic acid, salicylic acid, β

-hydroxybutyric acid, aleuritic acid and tropic acid, and mixtures thereof, and even more preferably from the group consisting of lactic acid, glycolic acid and ethylglycolic acid, and mixtures thereof.

3. Pharmaceutical composition according to claim 1, in which the progestin(s) is(are) selected from the group consisting of natural progestins and progestins of type 1, 2 or 3, preferably type 3 progestins and even more preferably from norgestimate, desogestrel, 3-ketodedogestrel, gestodene and mixtures thereof.

4. Pharmaceutical composition according to claim 1, in which the oestrogen(s) is(are) selected from the group consisting of natural oestrogens:

17β

-oestradiol, oestrone, equine conjugated oestrogens, estriol, phytoestrogens;

semi-natural oestrogens;

oestradiol valerate;

or synthetic oestrogens;

ethinyl-estradiol, preferably being 17β

-estradiol.

5. Pharmaceutical composition according to claim 1, in which the progestin content is between 0.01% and 5%, preferably between 0.02% and 3% and even more preferably between 0.03% and 2%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

6. Pharmaceutical composition according to claim 1, in which the oestrogen content is between 0.01% and 5%, preferably between 0.02% and 3% and even more preferably between 0.03% and 2%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

7. Pharmaceutical composition according to claim 1, in which the content of percutaneous absorption promoter(s) is between 0.1% and 20%, preferably between 0.2% and 10% and even more preferably between 0.5% and 5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

8. Pharmaceutical composition according to claim 1, which is in the form of a gel, a solution, a cream, a lotion, a spray, an ointment, an aerosol or a patch, preferably in the form of a gel.

9. Pharmaceutical composition according to claim 1, comprising at least one non-aqueous solvent preferably selected from volatile compounds such as ethanol, isopropanol or ethyl acetate, preferably being ethanol and/or isopropanol and even more preferably being ethanol.

10. Pharmaceutical composition according to claim 9, in which the content of non-aqueous solvent is between 10% and 90%, preferably between 20% and 80% and even more preferably between 40% and 70%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

11. Pharmaceutical composition according to claim 1, comprising at least one aqueous vehicle selected from the group consisting of alkalinizing or basic buffer solutions such as a phosphate buffer solution such as dibasic or monobasic sodium phosphate, a citrate buffer solution such as sodium citrate or potassium citrate, or purified water.

12. Pharmaceutical composition according to claim 11, in which the content of aqueous vehicle is between 1% and 80%, preferably between 10% and 70% and even more preferably between 20% and 60%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

13. Pharmaceutical composition according to claim 1, comprising at least one co-solvent such as polyols or polyglycols such as, for example, glycerol (or glycerine), propylene glycol or polyethylene glycol.

14. Composition according to claim 13, in which the co-solvent content is between 0.5% and 20%, preferably between 3% and 10% and more preferably between 4% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

15. Pharmaceutical composition according to claim 1, comprising at least one gelling agent preferably selected from the group consisting of carbomers, cellulose derivatives, poloxamers and poloxamines.

16. Pharmaceutical composition according to claim 15, in which the content of gelling agent is between 0.2% and 30%, preferably between 0.5% and 10% and even more preferably between 0.3% and 5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.

17. Pharmaceutical composition according to claim 15, comprising at least one neutralizer.

18. Pharmaceutical composition according to claim 17, in which the neutralizer/gelling agent ratio is between 10/1 and 0.1/1, preferably between 7/1 and 0.5/1 and even more preferably between 4/1 and 1/1.

19. Pharmaceutical composition according to claim 17, in which the neutralizer(s) is(are) selected from the group consisting of triethanolamine, sodium hydroxide, ammonium hydroxide, potassium hydroxide, arginine, aminomethyl propanol and tromethamine.

20. Pharmaceutical composition according to claim 1, having a pH of between 2 and 9, preferably between 3 and 7 and even more preferably between 3 and 6.

21. Process for preparing the pharmaceutical composition in the form of a gel according to claim 1, comprising the following successive steps:

progestin(s) and/or oestrogen(s) are dissolved, with stirring, in a mixture of non aqueous vehicle and absorption promoter;

an aqueous vehicle such as water or buffer solution is added, with stirring, to the mixture obtained;

a co-solvent such as propylene glycol is optionally added;

a gelling agent is then incorporated into the mixture, with stirring;

a neutralizer is optionally added to the mixture, with stirring.

22. Method for the treatment of a physiological condition associated with an oestro-progestin deficiency, comprising administering an effective amount of a pharmaceutical composition according to claim 1 to a subject.

23. Method according to claim 22, in which the physiological condition is selected from the group consisting of:

disorders of the cycle or disruptions in the menstrual regularity,

premenstrual syndrome,

mastodynia,

functional ovarian cysts,

mittelschmertz syndrome,

dysmenorrhoea.