Steroid carboxylic acid esters, compositions containing steroid carboxylic acid esters, and use of said compositions in local topical applications for cosmetic or dermatological purposes

Abstract

The invention relates to the use of a steroid-3-carboxylic acid ester, a steroid-4 carboxylic acid ester or a steroid-17 carboxylic acid ester of a steroid, selected from the group of androstanones, androst-4-ene-diones, androst-5-ene-diones, dehydroepiandrosterones, androstenetriones or testosterones, with an acyl group of the carboxylic acid ester ##STR00001##
where R is selected from alkyl with at least two carbon atoms or cycloalkyl, or with the use of a compound containing these steroid carboxylic acid esters for local topical application for cosmetic or dermatological purposes. Moreover, this invention also relates to steroid carboxylic acid esters and their compounds used for local topical application.

Claims

1. A method of improving the condition of the skin in a subject in need thereof, comprising topically applying locally for cosmetic or dermatological purposes to a subject, wherein the cosmetic or dermatological purposes comprise reduction of cellulite, general skin firming, reduction of stretch marks, prevention of scar formation, reduction in the size of scars after their formation, lessening of allergy-related skin irritations or irritations caused by insect bites, ultraviolet radiation, or X-rays and general itchiness of the skin, a composition comprising a steroid-4 carboxylic acid ester that is a derivative of 4-hydroxyandrostenedione according to the following structure: ##STR00007## where R is selected from alkyl with at least two carbon atoms or cycloalkyl, wherein the steroid-4 carboxylic acid ester is contained in the composition in an amount of 0.001 to 10% by weight based on the total amount of the composition.

2. The method in accordance with claim 1, wherein the acyl group of the steroid-4 carboxylic acid ester is free of polar substitutes.

3. The method in accordance with claim 1, wherein the radical R of the acyl group is an alkyl radical with at least two carbon atoms and wherein the alkyl radical is either unbranched or branched.

4. The method in accordance with claim 1, wherein the radical R of the acyl group is an alkyl radical with at least two carbon atoms and wherein the alkyl radical has been selected from ethyl, propyl, isopropyl, butyl, sec-butyl (1-methylpropyl), isobutyl (2-methylpropyl), tert-butyl (1,1-dimethylethyl), pentyl, hexyl and structural isomers of pentyl or hexyl.

5. The method in accordance with claim 1, wherein the radical R of the acyl group is a cycloalkyl radical and wherein the cycloalkyl radical has been selected from cyclopropane, cyclopentane or cyclohexane.

6. The method in accordance with claim 1, wherein the steroid-4 carboxylic acid ester is 4-O-propionyl-androstene-3,17-dione, 4-O-butyryl-androstene-3,17-dione, 4-O-valeryl-androstene-3,17-dione, 4-O-caproyl-androstene-3,17-dione or 4-O-enantyl-androstene-3,17-dione.

7. The method in accordance with claim 1, wherein the steroid-4 carboxylic acid ester is 4-O-propionyl-androst-4-ene-3,17-dione with the formula ##STR00008##

8. The method in accordance with claim 1, wherein the steroid-4 carboxylic acid ester is contained in the composition in an amount of 0.001 to 5% by weight based on the total amount of the composition.

9. A method of improving the condition of the skin in a subject in need thereof, comprising topically applying locally for cosmetic or dermatological purposes to a subject, wherein the cosmetic or dermatological purposes comprise reduction of cellulite, general skin firming, reduction of stretch marks, prevention of scar formation, reduction in the size of scars after their formation, lessening of allergy-related skin irritations or irritations caused by insect bites, ultraviolet radiation, or X-rays and general itchiness of the skin, a composition comprising a steroid-4 carboxylic acid ester that is a derivative of 4-hydroxyandrostenedione according to the following structure: ##STR00009## where R is selected from alkyl with at least two carbon atoms or cycloalkyl, and wherein the steroid-4 carboxylic acid ester is contained in the composition formulated as an ointment, cream, gel, oil, emulsion or lotion.

Description

EXAMPLE 1

(1) Formulation and Production of an Emulsion in Accordance with the Invention

(2) TABLE-US-00001 Phase INCI name % by weight A Aqua/water 77.9968 Disodium EDTA 0.1000 Panthenol 0.1000 Sorbitol 0.4000 Xanthan 0.5000 Glycerin 5.0000 Butylene glycol 1.6000 Ethylhexylglycerin 0.4000 B Cetyl alcohol 2.0000 Dimethicone 1.1000 Potassium cetyl phosphate 0.7000 C20-22 alkyl phosphate 1.8000 C20-22 alkyl alcohols 1.5000 Caprylic/capric triglyceride 3.0000 C Propylene glycol 1.0000 Chlorphenesin 0.2000 Phenoxyethanol 0.7000 D Jojoba oil 0.5000 Tocopheryl acetate 0.0500 Lecithin 0.0210 Tocopherol 0.0045 Ascorbyl palmitate 0.0030 Citric acid 0.0015 Ascorbyl tetraisopalmitate 0.1000 E Phytanic acid 0.0800 Lactic acid 0.4500 Sodium hydroxide 0.2400 F 4-O-propionyl-androst-4-ene-3,17-dione 0.2000 Aromatic substances/fragrance 0.2500 H Caramel 0.0032

(3) Preparation:

(4) The ingredients for Phase A are mixed and heated to 70 to 75 C. white stirring. The ingredients for Phase 8 are mixed, heated to 70 to 75 C. and added to Phase A while stirring. The mixture of A and B is cooled to 50 C. while stirring. Phase C is added, while continuing to stir. The ingredients for Phase D are mixed and added to the Phase A+B+C while stirring. The ingredients for Phase E are mixed and added to the Phase A+B+C+D while stirring. Phase F is added to the A+B+C+D+E Phase while stirring at a maximum temperature of 30 to 35 C. Phase G is added to the A+B+C+D+E+F Phase while stirring at a maximum temperature of 25 C. Phase H is added to the A+B+C+D+E+F+G Phase while stirring at a maximum temperature of 25 C. All steps of this preparation process can be carried out in a vacuum mixer to obtain particularly homogeneous compounds that do not contain air bubbles.

EXAMPLE 2

(5) Formulation and Production of a Cream in Accordance with the Invention

(6) TABLE-US-00002 Phase INCI name % by weight A Aqua/water 78.9830 Disodium EDTA 0.1500 Sorbitol 0.4000 Glycerin 2.0000 Ethylhexylglycerin 0.4000 Xanthan 0.3000 B Cetearyl alcohol 1.9000 Caprylic/capric triglyceride 1.7000 Cetearyl glucoside 0.7900 Glyceryl stearate 0.9000 Ethylhexyl palmitate 1.6000 Cetyl palmitate 1.6000 Dicaprylyl carbonate 2.0000 Shea butter 0.5000 White beeswax-Cera alba 0.3000 Sodium polyacrylate 1.0000 PEG-100 stearate 0.9000 Hydrogenated polydecene 0.8000 Trideceth-6 0.1600 C Chlorphenesin 0.2000 Phenoxyethanol 0.7000 D Jojoba oil 0.5000 Tocopheryl acetate 0.1000 Lecithin 0.0350 Tocopherol 0.0075 Ascorbyl palmitate 0.0050 Citric acid 0.0025 E Lactic acid 0.9000 Sodium hydroxide 0.6000 F Phytanic acid 0.2000 G Ascorbyl tetraisopalmitate 0.1000 H 4-O-propionyl-androst-4-ene-3,17-dione 0.1000 I Aromatic substances/fragrance 0.1670

(7) Preparation:

(8) The ingredients for Phase A are mixed and heated to 70 to 75 C. while stirring. The ingredients for Phase B are mixed, heated to 70 to 75 C. and added to Phase A while stirring. The mixture of A and B is cooled to 50 C. while stirring. Phase C is added, while continuing to stir. The ingredients for Phase D are mixed and added to the Phase A+B+C while stirring. The ingredients for Phase E are mixed and added to the Phase A+B+C+D while stirring. Phase F is added to the A+B+C+D+E Phase while stirring at a maximum temperature of 35 to 4 C. Phase G is added to the A+B+C+D+E+F Phase while stirring at a maximum temperature of 35 to 40 C. Phase H is added to the A+B+C+D+E+F+G Phase while stirring at a maximum temperature of 30 to 35 C. Phase I is added to the A+B+C+D+E+F+G+H Phase while stirring at a maximum temperature of 25 C. All steps of this preparation process can be carried out in a vacuum mixer to obtain particularly homogeneous compounds that do not contain air bubbles.

EXAMPLE 3

(9) Formulation of Another Cream in Accordance with the Invention

(10) TABLE-US-00003 Description % by weight Aqua/water 56.8 Propylene glycol 25.0 Isopropyl myristate 6.0 Cetearyl stearyl alcohol 6.0 Stearyl alcohol 2.0 Polysorbate 80 (polyoxyethylene(20)- 2.0 sorbitan-monooleate) Sorbitan monostearate 1.0 Glycerol monostearate 1.0 4-O-propionyl-androst-4-ene-3,17-dione 0.1 Hyaluronic acid 0.1

EXAMPLE 4

(11) Formulation of Another Cream in Accordance with the Invention

(12) TABLE-US-00004 INCI name % by weight Aqua/water 62.85 Jojoba oil 6.05 Cocoglycerides 5.95 Dimethyl isosorbide 5.00 Glycerin 4.20 Sorbitol 4.00 Shea butter 3.00 Polyglyceryl-3-methylglucose distearate 3.00 Cetearyl alcohol 2.20 Yellow beeswax-Cera flava 1.00 Tocopheryl acetate 1.00 Polysol AC: 0.70 Phenoxyethanol Dehydroacetic acid Sorbic acid Benzoic acid Lactic acid 4-O-propionyl-androst-4-ene-dione 0.09 Xanthan 0.25 Aromatic substances/fragrance 0.20 Tetrasodium iminodisuccinate 0.10 Ethylhexylglycerin 0.10 Lactic acid, 80% 0.10 Ascorbyl tetraisopalmitate 0.10 Phytanic acid 0.05 Controx VP: 0.04 Lecithin Ascorbyl palmitate Hydrogenated palm glycerides citrate Tocopherol Sodium hydroxide 0.02

EXAMPLE 5

(13) Formulation of an Oil-Based Gel in Accordance with the Invention

(14) TABLE-US-00005 Description % by weight Olive fruit oil 45.37 Caprylic/capric triglycerides 31.40 Glycerin 15.00 Polyglyceryl-5-oleate 6.00 Aqua/water 1.88 4-O-propionyl-androst-4-ene-3,17-dione 0.15 Tocopherol, sunflower oil 0.20

Results of a Clinical Study With a Cream Containing 4-O-propionyl-androst-4-ene-3,17-dioneEfficacy in the Treatment of Cellulite

(15) In a study carried out by an independent dermatological institute (Dermatest, Mnster), a cream containing 0.10% 4-O-propionyl-androst-4-ene-3,17-dione was tested on female test subjects for efficacy and tolerability.

(16) Trial Protocol:

(17) The trial involved 20 female test subjects (aged between 32 and 58 years, average age 45.1 years). One test subject prematurely terminated the trial after 8 weeks due to pregnancy; one new test subject (21st test subject) was incorporated at the beginning of the ninth week.

(18) The cream was applied once a day over a period of 12 weeks. The efficacy and tolerability (skin elasticity, thigh circumference, width and height of the protruding lobules) were evaluated after 4, 3 and 12 weeks.

(19) Efficacy:

(20) Skin Elasticity

(21) The skin elasticity was measured with a Cutometer. The skin elasticity increased in 100% of the test subjects. After 4 weeks the average increase was 14%, whereas after 12 weeks the average increase was 22.42%, 95% of the test subjects experienced a subjective improvement in skin elasticity.

(22) Surface Area of the Fat Lobules

(23) A surprising effect was observed with regard to the size of the protruding fat lobules that are responsible for the characteristic appearance of cellulite. The surface area corresponding to their size was measured during an ultrasound examination.

(24) The surface area of the fat lobules was reduced in 100% of the test subjects. After 4 weeks the surface area of the fat lobules had been reduced by an average of 23.24%, after 8 weeks the average reduction in the surface area was 34.51% and after 12 weeks the average reduction in the surface area of the fat lobules was 44.06%.

(25) According to a statement made by the independent research institute, such an effect has thus far not been observed in any competing product.

(26) Thigh Circumference

(27) The thigh circumference was reduced in 100% of the test subjects. After 4 weeks, the thigh circumference of the test subjects had been reduced by an average of 0.6 cm or 1.04%, whereas after 12 weeks the average reduction in thigh circumference was 1.87 cm or 3.25%.

(28) Further Options for Use in Cosmetic Products a) Stretch marks/striae b) Wrinkles (anti-ageing) c) Skin care following radiation therapy (oncological care)

(29) Each of the product ideas for the treatment of stretch marks/striae and scar care is the result of repeated positive observations made during the use of the cream containing 4-O-propionyl-androst-4-ene-3,17-dione; in all three applications the cream containing 4-O-propionyl-androst-4-ene-3,17-dione yielded clearly better results than products already on the market.

(30) All features of the invention can be material to the invention both individually and in any combination. Further advantages and advantageous embodiments of the invention are presented in the claims.