EP1414403A1

EP1414403A1 - Composition containing a steroid and a glycol

Info

Publication number: EP1414403A1
Application number: EP02770038A
Authority: EP
Inventors: Jean-Thierry Simonnet
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2001-07-27
Filing date: 2002-07-18
Publication date: 2004-05-06
Also published as: FR2827764A1; FR2827764B1; WO2003011244A1; US20040186085A1

Abstract

The invention concerns a composition containing, in a physiologically acceptable medium, at least a steroid selected among: DHEA and a metabolic or chemical derivative thereof, characterised in that it further comprises dipropylene glycol. The dipropylene glycol enables to solubilize the steroid and prevent its recrystallization. The invention also concerns cosmetic and dermatological uses of said composition, in particular for preventing or treating time-induced or actinic skin aging symptoms.

Description

COMPOSITION CONTAINING A STEROID AND A GLYCOL

The present invention relates to a composition containing, in a physiologically acceptable medium, at least one steroid chosen from: DHEA and a metabolic or chemical derivative thereof, characterized in that it also comprises dipropylene glycol.

DHEA, or dehydroepiandrosterone, is a natural steroid produced primarily by the adrenal cortex. It is known for its ability to promote keratinization of the epidermis (JP-0.7 196 467), or in the treatment of dry skin, due to its ability to increase endogenous production and sebum secretion and to strengthen the skin. barrier effect of the skin (US Pat. No. 4,496,556). The use of DHEA to remedy atrophy of the dermis by inhibiting the loss of collagen and connective tissue has also been described in US Pat. No. 5,843,932. It has finally been proposed to use DHEA sulfate to treat various signs of aging such as wrinkles, loss of radiance of the skin and sagging skin (EP-0723 775).

Among the metabolites of DHEA, particular attention has been paid in recent years to 7α-hydroxy DHEA. It has indeed been shown that this metabolite, which does not have the hormonal activity of DHEA, makes it possible to increase the proliferation of fibroblasts and the viability of human keratinocytes and has anti-radical effects (WO 98/40074). It has also been demonstrated in rats (WO 00/28996) that 7α-hydroxy DHEA increases the thickness of the dermis and the elastin and collagen content of the skin. It has thus been suggested to use this metabolite of DHEA to prevent and / or treat the harmful effects of UV on the skin, fight against wrinkles and increase the firmness and tone of the skin.

We therefore understand the advantage that there may be in using DHEA and its derivatives in cosmetic or dermatological compositions.

However, these steroids only dissolve with difficulty in aqueous and hydroalcoholic media, which limits their formulation in cosmetic or dermatological compositions. They therefore tend to recrystallize. However, the formation of poorly controlled size results in poor bioavailability of DHEA or its derivatives in the skin. This results in a more or less significant loss of effectiveness of the compositions containing them, depending on the degree of recrystallization, which goes against the objective sought. In addition, this recrystallization can modify the overall stability of these compositions as well as their appearance, which can divert the user from them.

Solutions have therefore been proposed by the Applicant to dissolve DHEA as well as its precursors and chemical and biological derivatives. It has thus been suggested to associate DHEA with 2-alkyl alkanols or alcohols from Guerbet (CA-2 343 426) or also with liposoluble UV filters (FR 2 803 514).

However, for certain cosmetic applications of DHEA, these solutions are not always well suited. In particular, the use of relatively soluble liposoluble UV filters (for example greater than 10% by weight) can lead to problems of intolerance and a relatively oily feel of the compositions containing DHEA, which is not always cosmetically desirable.

In addition, the solubilization in Guerbet alcohols of the most polar derivatives of DHEA does not always lead to satisfactory results in emulsion. Indeed, these derivatives have a high capacity for so-called Ostwald ripening which leads to their rapid recrystallization in emulsion, by transfer of these derivatives from the fatty phase containing them to the aqueous phase of the emulsion.

There therefore remains the need for compounds which make it possible to dissolve DHEA and its derivatives while avoiding their recrystallization as an emulsion and which do not adversely affect the cosmetic properties, in particular the feel, of the emulsion obtained.

The Applicant has now surprisingly found that these steroids can be easily dissolved in certain glycols.

A subject of the present invention is therefore a composition containing, in a physiologically acceptable medium, at least one steroid chosen from: DHEA and a metabolic or chemical derivative thereof, characterized in that it further comprises dipropylene glycol.

It also relates to a process for the solubilization of at least one steroid chosen from: DHEA and / or a metabolic or chemical derivative thereof, comprising the step consisting in mixing said steroid with dipropylene glycol.

The mixing can be carried out cold, at room temperature or hot, for example at 75 ° C., generally with stirring.

DHEA has the following formula (I):

The DHEA which can be used according to the invention is for example available from the company AKZO NOBEL.

The term “metabolic derivatives” of DHEA means in particular 7αOH-DHEA, 7βOH-DHEA and 7-keto-DHEA, without this list being limiting. 7αOH-DHEA is preferred for use in the present invention.

The term “chemical derivative” of DHEA means in particular the 3-alkyl esters of 7-oxo DHEA and in particular the 3β-acetoxy-7-oxo DHEA sold by the company HUMANETICS under the trade name 7-Keto®.

Other chemical derivatives of DHEA suitable for carrying out the present invention are the derivatives of formula (1):

(D

in which: Ri and R ₂ are independently chosen from:

• a C _r Cι ₂ alkyl group, saturated or unsaturated, linear, branched or cyclic which may optionally contain one or more heteroatoms, and optionally substituted by one or more groups chosen from -OR 'and / or -SR' and / or - COOR 'and / or - NR'R' and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle can advantageously be chosen from an indole, a pyrimidine, a piperidine, a morpholine, pyran, furan, piperazine, pyridine;

• an alkylcarbonyl group, the C ₁ -C ₂₄ alkyl part of which is saturated or unsaturated, linear, branched or cyclic, and optionally substituted by one or more groups chosen from -OR 'and / or -SR' and / or -COOR 'and / or -NR'R' and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle can advantageously be chosen from an indole, a pyrimidine, a piperidine, a morpholine, a pyrane, furan, piperazine, pyridine;

an arylcarbonyl group, preferably a phenylcarbonyl, or an arylalkylcarbonyl group, preferably a benzylcarbonyl, optionally substituted by one or more groups -OR 'and or -SR' and / or -COOR 'and / or -NR'R' and / or halogen and or aryl and / or heterocycle;

an O = P (OH) OR 'group; a group (O) ₂ SOR '; • a trialkylsilyl group (SiR ' ₃ ) in which the 3 R' groups can be identical or different;

• a carbonyloxyalkyl group (R'OCO);

• a carbonylaminealkyle group (R'NHCO);

in which R 'is chosen from a hydrogen atom, a C 1 -C ₁₂ , preferably C ₁ -C ₆ , saturated or unsaturated, linear, branched or cyclic alkyl group which may optionally contain one or more heteroatoms, optionally functionalized by one or more groups -OR ", -COOR", halogen, -NR'R "; or by an aryl group, preferably a phenyl, optionally functionalized by one or more groups - OR", -COOR ", halogen or - NR "R"; R "representing a hydrogen atom, an alkyl chain, preferably C 1 -C ₆ , saturated or unsaturated, linear, branched or cyclic, it being understood that in each of the groups -NR'R 'and -NR'R ", the substituents R ', respectively R", are identical or different.

Among the derivatives of formula (1), there may be mentioned in particular the diesters of 7-OH-DHEA and more preferably 3-O-acetyl-7-benzoyloxy-dehydroepiandrosterone which is in particular available from the company GATTEFOSSE under the trade name 3-acetoxy-7-benzoate DHEA.

The composition according to the present invention contains, as a solubilizer for the above steroids, dipropylene glycol.

This glycol can be used as the main solvent, in which case it makes it possible to dissolve the steroid in an aqueous medium, or as a secondary solvent. In the latter case, they

^• can be added to a composition containing fat-soluble UV filters or Guerbet alcohols as main solvents, so as to increase the solubility of the steroid in the aqueous phase when it transfers therefrom from the oily phase containing the main solvent. Dipropylene glycol therefore makes it possible both to dissolve the steroid, such as DHEA, and to stabilize it vis-à-vis the ripening of Ostwald.

The steroid concentration in the composition according to the invention is advantageously between 0.001% and 20% by weight, preferably between 0.01 and 10% by weight, more preferably between 0.1 and 5% by weight, relative to the total weight of the composition. In addition, the weight amount of glycol according to the invention advantageously represents from 1 to 40 times the weight amount of steroid in the composition according to the invention, that is to say that by way of indication, the glycol may represent 0.01% to 50%, better still, from 1 to 20%, of the total weight of the composition.

The composition according to the invention can be in all dosage forms normally used for topical application to the skin, in particular in the form of an aqueous solution, a gel, an oil-in-water emulsion, an organogel as described in application FR 2 794 998, of an emulsion without surfactant stabilized by polymeric particles (as described in application EP-0 864 320) or by mineral particles (as described in applications WO 00 / 98301, WO 00/07548, WO 00/07549 and WO 00/07550), of a microemulsion or of a nanoemulsion. The content of these patents is incorporated herein by reference.

This composition can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foam. or a gel. It can optionally be applied to the skin in the form of an aerosol. It can be used as a care product and / or as a make-up product for the skin, or as a hair product, for example as a shampoo or conditioner.

In a known manner, the composition of the invention may also contain the adjuvants usual in the cosmetic and dermatological fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers, pigments, odor absorbers and coloring matters. The amounts of these various adjuvants are those conventionally used in the fields considered, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. These adjuvants, as well as their concentrations, must be such that they do not harm the advantageous properties of the steroids according to the invention.

When the composition according to the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The fats, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the field under consideration. The emulsifier and the coemulsifier are preferably present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

As fats which can be used in the invention, it is possible to use solubilizers based on 2-alkyl alkanols and their esters, oils and in particular mineral oils (petroleum jelly oil), oils of vegetable origin (avocado oil) , soybean oil), oils of animal origin (lanolin), synthetic oils (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums and in particular silicone gums can also be used as fats.

As emulsifiers and coemulsifiers which can be used in the invention, there may be mentioned, for example, fatty acid esters of polyethylene glycol such as PEG-100 stearate, PEG-50 stearate and PEG-40 stearate; fatty acid and polyol esters such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween® 20 or Tween® 60, for example; alkyl ethers of saturated or unsaturated fatty alcohols, linear or branched, in Cι ₀ -C ₂₀ and of polyethylene glycol such as ethers of stearyl alcohol and of PEG available under the trade names BRU 72 or BRU 721, for example; alkyl ethers of glycerol or polyols; alkyl- and / or polyalkyl ethers of glucose or of sucrose such as the products sold under the names CRODESTA F10, F20, F50, F70, F110 or F160, for example; and their mixtures.

As hydrophilic gelling agents, mention may be made in particular of carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, cite modified clays such as bentones, metal salts of fatty acids and hydrophobic silica.

According to a preferred embodiment of the invention, the composition may contain, in addition to dipropylkene glycol, at least one other (poly) alkylene glycol and / or an ester of (poly) alkylene glycol.

As examples of other alkylene glycols, mention may be made of ethylene glycol, propylene glycol, butylene glycol and pentylene glycol, hexylene glycol.

As examples of other polyalkylene glycols, mention may be made of polyethylene glycol comprising from 2 to 20 ethylene glycol units.

Finally, as esters of (poly) alkylene glycols, mention may be made of mono-, di- and triesters of C _r C ₆ acid and of alkylene glycol, such as propylene glycol acetate.

The composition according to the invention finds in particular an application in the prevention and the treatment of the signs of chronological or actinic aging.

The present invention therefore also relates to the cosmetic use of the composition mentioned above for preventing or treating the signs of chronological or actinic skin aging.

It relates in particular to the cosmetic use of this composition for preventing or treating loss of skin firmness and / or dull complexion and / or dilation of pores and / or pigmentation disorders of the skin or hair. The invention also relates to the cosmetic use of this composition for preventing or treating hyperseborrhea and / or the imperfections linked to hyperseborrhea and / or dandruff and / or hair loss.

The invention will now be illustrated by the following nonlimiting examples. In these examples, the quantities are indicated in percentage by weight, unless otherwise indicated.

EXAMPLES

EXAMPLE 1 Solubilization of DHEA

The solubility of DHEA was evaluated at room temperature in different solvents. To do this, the DHEA was dispersed, in excess, in the solvent concerned, previously brought to 60 ° C. This temperature was maintained for one hour with stirring with the magnetic bar. The suspension was then brought to room temperature (25 ° C). After 24 hours, the suspension was centrifuged to remove the crystals of unsolved DHEA. The supernatant was removed and the absence of DHEA crystals was checked by cross-polarization optical microscopy. This supernatant was then analyzed by HPLC. It is considered that the amount of DHEA detected corresponds to the maximum solubility thereof in the solvent concerned.

The results are collated in the table below.

It is therefore clear from this Table that dipropylene glycol is a much better solvent for DHEA than the solvents conventionally used in the fields cosmetic and pharmaceutical, such as glycerol and sorbitol, and even other (poly) alkylene glycols such as polyethylene glycol (400 EO) and propylene glycol. EXAMPLE 2 Cosmetic Composition

Phase A

Glycerol stearate 2.5%

Polyethylene glycol stearate (8 EO) 2.5%

Stearic acid 1.0%

Preservative 0.1%

Hexyl dodecanol 8.0%

15% caprylic / capric acid triglycerides

DHEA 1%

Phase B Triethanolamine 0.25% Preservative 0.2% Dipropylene glycol 10% Distilled water qs 100%

Phase C Carbomer 0.3% Distilled water 14.95% Neutralizer 0.25%

The above composition can be prepared as follows. Phase A and phase B are brought to 75 ° C, separately. Phase B is introduced into phase A with Moritz-type rotor-stator stirring. The temperature is maintained at 75 ° C. After 30 minutes of stirring, three passes are made to the high pressure homogenizer, between 200 b and 900 b. The suspension is then brought back to room temperature before phase C is dispersed using a deflocculator. A white emulsion of oil-in-water type is obtained containing DHEA oleosomes.

This composition can be used to prevent or treat the signs of skin aging such as wrinkles and fine lines and sagging skin. EXAMPLE 3 Cosmetic Composition

A lotion having the following composition is prepared, conventionally for a person skilled in the art:

3β-acetoxy-7-oxo DHEA 1%

Dipropylene glycol 25% Propylene glycol 20%

Glycerol 30%

100% distilled water

This lotion can be used, in particular, to reduce pigment spots on the hands and décolleté.

Example 4 Cosmetic Composition

An emulsion having the following composition is prepared, in the same manner as the composition of Example 2:

Phase A:

Diglycerol distearate 2.4% Sorbitan stearate (4OE) 2.1%

Monosodium salt of N Stearoyl L glutamic acid 0.7%

Keto-stearyl alcohol 1%

Vaseline 2%

Stearyl heptanoate 5% Isocetyl stearate 8%

Octyl dodecanol 8%

Capric-caprylic triglycerides 5%

Cyclopentasiloxane 5%

7OH-DHEA 0.8% Pnase B

Dipropylene glycol 25%

Preservatives 1% Distilled water 25%

Phase C

Carbomer 0.2%

Triethanolamine 0.1% Water

This composition is well suited for very dry skin.

Claims

1. Composition containing, in a physiologically acceptable medium, at least one steroid chosen from: DHEA and a metabolic or chemical derivative thereof, characterized in that it also comprises dipropylene glycol.

2. Composition according to claim 1, characterized in that said steroid is DHEA.

3. Composition according to claim 1, characterized in that said metabolic derivative of DHEA is chosen from: 7αOH-DHEA, 7βOH-DHEA and 7-keto-DHEA. '

4. Composition according to claim 1, characterized in that said chemical derivative of DHEA is a 3-alkylester of 7-oxo DHEA.

5. Composition according to claim 4, characterized in that said chemical derivative of DHEA is 3β-acetoxy-7-oxo DHEA.

6. Composition according to claim 1, characterized in that said chemical derivative of DHEA is represented by formula (1):

d)

in which :

R and R ₂ are independently chosen from:

• a C _r Cι ₂ alkyl group, saturated or unsaturated, linear, branched or cyclic which may optionally contain one or more heteroatoms, and optionally substituted by one or more groups chosen from -OR 'and or -SR' and / or -COOR 'and / or - NR'R' and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle can advantageously be chosen from an indole, a pyrimidine, a piperidine, a morpholine, a pyran, a furan, a piperazine, a pyridine;

• an alkylcarbonyl group, the C _r C ₂₄ alkyl part of which is saturated or unsaturated, linear, branched or cyclic, and optionally substituted by one or more groups chosen from -OR 'and / or -SR' and / or -COOR ' and / or -NR'R 'and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle can advantageously be chosen from an indole, a pyrimidine, a piperidine, a morpholine, a pyran , furan, piperazine, pyridine;

• an arylcarbonyl group, preferably a phenylcarbonyl, or an arylalkylcarbonyl group, preferably a benzylcarbonyl, optionally substituted by one or more groups -OR 'and / or -SR' and / or -COOR 'and / or -NR'R' and / or halogen and or aryl and / or heterocycle;

• a group O = P (OH) OR '; • a group (O) ₂ SOR ';

• a trialkylsilyl group (SiR ' ₃ ) in which the 3 R' groups can be identical or different;

• a carbonyloxyalkyl group (R'OCO);

• a carbonylaminealkyle group (R'NHCO);

in which R 'is chosen from a hydrogen atom, a C _r Cι ₂ alkyl group, preferably C _r C ₆ , saturated or unsaturated, linear, branched or cyclic which may optionally contain one or more heteroatoms, optionally functionalized by one or more groups -OR ", -COOR", halogen, -NR "R"; or by an aryl group, preferably a phenyl, optionally functionalized by one or more groups - OR ", -COOR", halogen or -NR "R";

R "representing a hydrogen atom, an alkyl chain, preferably C ^ Ce, saturated or unsaturated, linear, branched or cyclic, it being understood that in each of the groups -NR'R 'and -NR" R ", the substituents R ', respectively R ", are the same or different.

7. Composition according to claim 6, characterized in that the chemical derivative of DHEA is 3-O-acetyI-7-benzoyloxy-dehydroepiandrosterone.

8. Composition according to any one of claims 1 to 7, characterized in that it comprises from 0.1 to 5% by weight of steroid, relative to the total weight of the composition.

9. Composition according to any one of claims 1 to 8, characterized in that the weight amount of glycol represents from 1 to 40 times the weight amount of steroid in the composition.

10. Composition according to any one of claims 1 to 8, characterized in that the glycol represents from 1 to 20% of the total weight of the composition.

11. Composition according to any one of claims 1 to 10, characterized in that it also contains at least one other (poly) alkylene glycol and / or an ester of

(poly) alkylene glycol.

12. Cosmetic use of the composition according to any one of claims 1 to 11 for preventing or treating the signs of chronological or actinic skin aging.

13. Cosmetic use of the composition according to any one of claims 1 to 11 for preventing or treating loss of firmness of the skin and / or dull complexion and / or dilation of pores and / or pigmentation disorders of the skin or hair.

14. Cosmetic use of the composition according to any one of claims 1 to 11 for preventing or treating hyperseborrhea and / or the imperfections linked to hyperseborrhea and / or dandruff and / or hair loss.

15. A method of solubilizing at least one steroid chosen from: DHEA and / or a metabolic or chemical derivative thereof, comprising the step consisting in mixing said steroid with at least one glycol chosen from hexylene glycol and dipropylene glycol.