Compositions comprising a compound of low solubility and a lipophilic amino acid derivative, and corresponding uses and processes

The present invention relates to compositions based on lipophilic amino acid derivatives, to their uses and to a process for the solubilization of at least one compound of low solubility in water.

It is known to use active agents in cosmetic and / or dermatological compositions, for example with a view to treating or treating or bringing beneficial effects to the skin. However, the use of some of these active agents poses a problem insofar as they are in crystalline form and where they are hardly or not at all soluble in water.

Thus, if they are introduced as they are into cosmetic and / or dermatological compositions, they remain in the form of crystals, which makes the use of the composition containing them, ineffective for the treatment of the skin.

Generally and for some of them, it is possible to introduce them in hydroalcoholic form (water / ethanol), but the presence of alcohol is not always desirable, especially when applied to certain areas of the face, such as than the eye area.

There therefore remains the need to be able to introduce compounds of low solubility in cosmetic and / or dermatological compositions, in particular in the aqueous phase of such compositions.

“Low solubility” is understood here to mean compounds such as δa> 6 J^1/2 cm^-3/2 and having a solubility in water at 25 ° C of less than 1% by weight. A molecule is generally defined as being insoluble in water from a certain percentage (here 1%) when, at the macroscopic level, a precipitate appears or the solution becomes cloudy, and at the microscopic level, crystals appear.

As recalled in the book <nplcit id="ncit0001" npl-type="b"><text>“Properties of Polymers” by DWVan Krevelen 3th edition (Elsevier, 1990) page 200 and sq</text></nplcit>, the solubility of a compound in a given solvent is largely determined by its chemical structure.

The solubility parameter makes it possible to define a molecule with respect to the interaction forces in which it participates.

This so-called "Hansen" solubility parameter is obtained by the following equation: <maths id="math0001"><math display="block"><msup><mi mathvariant="normal">δ</mi><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">=</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">d</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">p</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">h</mi></msub><mn mathvariant="normal">2</mn></msup></math><img file="EP1269986B1_D0001.tif" /></maths>in which :<ul id="ul0001" list-style="none" compact="compact"><li>δ_d represents the forces of dispersion at the time of the shocks, known as London forces or Van der Waals forces resulting from the formation of dipoles induced during molecular shocks: <maths id="math0002"><math display="block"><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">d</mi></msub><mo mathvariant="normal">=</mo><mi mathvariant="normal">Σ</mi><mo>⁢</mo><msub><mi mathvariant="normal">F</mi><mi mathvariant="normal">d</mi></msub><mo mathvariant="normal">/</mo><mi mathvariant="normal">V</mi><mo>,</mo></math><img file="EP1269986B1_D0002.tif" /></maths></li><li>δ_p represents the molecular polarization forces or Debye interaction forces, that is to say the permanent dipole generated by the molecule considered when it is dissolved, it is calculated by: <maths id="math0003"><math display="block"><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">p</mi></msub><mo mathvariant="normal">=</mo><msup><mfenced><mi mathvariant="normal">Σ</mi><mo>⁢</mo><msup><msub><mi mathvariant="normal">F</mi><mi mathvariant="normal">p</mi></msub><mn>2</mn></msup></mfenced><mrow><mn>1</mn><mo>/</mo><mn>2</mn></mrow></msup><mo mathvariant="normal">/</mo><mi mathvariant="normal">V</mi><mo>,</mo></math><img file="EP1269986B1_D0003.tif" /></maths></li><li>and δ_h represents the specific interaction forces such as hydrogen, acid / base, donor / acceptor bonds, calculated by: <maths id="math0004"><math display="block"><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">h</mi></msub><mo mathvariant="normal">=</mo><msup><mfenced><mi mathvariant="normal">Σ</mi><mo>⁢</mo><msub><mi mathvariant="normal">F</mi><mi mathvariant="normal">h</mi></msub><mo mathvariant="normal">/</mo><mi mathvariant="normal">V</mi></mfenced><mrow><mn>1</mn><mo>/</mo><mn>2</mn></mrow></msup><mn>.</mn></math><img file="EP1269986B1_D0004.tif" /></maths></li></ul>

The parameters δ_d, δ_p and δ_h are expressed in (J / cm³)^1/2.

Each of the parameters δ_p and δ_h is not zero when the molecule considered comprises at least one heteroatom.

F_d, F_p, F_h being the molar constants of the interaction forces of the groups of atoms constituting the molecules and V the molar volume which can be determined by the method of <nplcit id="ncit0002" npl-type="s"><text>Fedors (Polymer Engineering and Science, February, 1974, Vol 14 n ° 2</text></nplcit>). V being the sum of the molar volumes of the radicals which make up the molecule considered, the value V for most of the radicals is given in the article by Fedors mentioned above.

To calculate the values ​​of F_d, F_p, F_h for a given molecule, it suffices to calculate the sum of the contributions of the radicals which compose said molecule. The values ​​of F_d, F_p, F_h have been established for most radicals, the book “Properties of Polymers” by DWVan Krevelen cited above contains in particular tables presenting these values ​​for many radicals.

In order to obtain an expression of the solubility in two components, we have also defined: <maths id="math0005"><math display="block"><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">at</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">=</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">p</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">h</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">=</mo><msup><mi mathvariant="normal">δ</mi><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">-</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">d</mi></msub><mn mathvariant="normal">2</mn></msup></math><img file="EP1269986B1_D0005.tif" /></maths> from where <maths id="math0006"><math display="block"><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">at</mi></msub><mo mathvariant="normal">=</mo><msup><mfenced><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">p</mi></msub><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><msub><mi mathvariant="normal">δ</mi><mi mathvariant="normal">h</mi></msub><mn mathvariant="normal">2</mn></msup></mfenced><mrow><mn mathvariant="normal">1</mn><mo mathvariant="normal">/</mo><mn mathvariant="normal">2</mn></mrow></msup></math><img file="EP1269986B1_D0006.tif" /></maths>

These notions of solubility and cohesion are defined in particular in the book: <nplcit id="ncit0003" npl-type="b"><text>“Properties of Polymers” by DWVan Krevelen 3th edition (Elsevier, 1990) chapter 7</text></nplcit> and in the article "<nplcit id="ncit0004" npl-type="s"><text>A method for estimating both the solubility parameters and molar volumes of liquids "RF Fedors, Polymer Engineering and Science, February 1974 vol.14 n ° 2 p147-154</text></nplcit>.

Within the meaning of the present invention, the inventors have defined the molecules of low solubility in water as being molecules having a solubility in water at 25 ° C of less than 1% by weight and such that δa&gt; 6 J^1/2 cm^-3/2.

It is often necessary to be able to dissolve easily in a physiologically acceptable medium molecules of low solubility in water. The solutions and compositions thus obtained are generally easy to implement and they can be applied with a minimum of discomfort. In addition, it is often necessary to be able to dissolve a sufficient quantity of these molecules of low solubility for their cosmetic or dermatological use, without recrystallization of these molecules or loss of solubility of the composition containing them. This instability would indeed result in a more or less significant loss of effectiveness of these compositions and / or in a modification of their appearance, which would risk diverting the user from them.

The Applicant has now discovered that lipophilic amino acid derivatives make it possible to unexpectedly increase the solubilization of these molecules of low solubility and to keep these molecules solubilized in compositions which are therefore stable.

A subject of the present invention is therefore a method of solubilizing at least one low solubility compound of formula (I '), said method comprising the essential step of mixing the low solubility compound with at least one lipophilic acid derivative amine, as well as a composition comprising, in a physiologically acceptable medium, at least one compound having a solubility in water at 25 ° C of less than 1% and such that δa&gt; 6 J^1/2 cm^-3/2 of formula (I ') and at least one lipophilic amino acid derivative.

By "physiologically acceptable medium" within the meaning of the present application, is meant a medium compatible with the skin including the scalp, the mucous membranes, the eyes and / or the hair.

By way of illustration, the lipophilic amino acid derivatives used within the meaning of the present application have made it possible to dissolve:<ul id="ul0002" list-style="dash" compact="compact"><li>more than 20% of aminophenol derivatives without recrystallization after three weeks at 25 ° C,</li><li>more than 15% of salicylic acid derivatives without recrystallization after three weeks at 25 ° C,</li><li>approximately 4% of diosgenin or hecogenin acetate without recrystallization after 24 hours at 25 ° C.</li></ul>

In the case of an emulsion, the use of one of these lipophilic amino acid derivatives makes it possible to overcome the limit traditionally imposed by the level of solubilizer, the cosmeticity of these solubilizers being generally prohibitive. In the context of the present invention, the emulsions retain a very acceptable cosmetic quality despite high solubilizing levels.

The lipophilic amino acid derivative used according to the invention is an amino acid ester of formula:         R '₁ (CO) N (R '₂) CH (R₃) (CH₂) n (CO) OR '₄in which :<ul id="ul0003" list-style="none" compact="compact"><li>n is an integer equal to 0.1 or 2,</li><li>R '₁ represents a C alkyl or alkenyl radical₅ at C₂₁, linear or branched,,</li><li>R '₂ represents a hydrogen atom or a C 1 alkyl group₁ at C₃,</li><li>R '₃ represents a radical chosen from the group formed by a hydrogen atom, a methyl group, an ethyl group, a linear or branched C alkyl radical₃ or C₄,</li><li>R '₄ represents a C 1 alkyl radical₁ at C₁₀ or C alkenyl₂ at C₁₀, linear or branched, or a sterol residue.</li></ul>

Preferably, the group R '₁(CO) - is an acyl group of an acid chosen from the group formed by capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, oleic acid, isostearic acid, 2-ethylhexanoic acid, coconut oil fatty acids, palm kernel oil fatty acids. These fatty acids may also have a hydroxyl group. Even more preferably, it will be lauric acid.

The part -N (R '₂) CH (R '₃) (CH₂)_not(CO) - the amino acid ester is preferably chosen from the following amino acids: glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, β-alanine, aminobutyric acid, aminocaproic acid, sarcosine, or N-methyl-β-alanine.

Even more preferably, it will be sarcosine.

The part of the amino acid esters corresponding to the group OR '₄ can be obtained from the alcohols chosen from the group formed by methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol, fusel oil, pentanol, hexanol, cyclohexanol, octanol, 2-ethylhexanol, decanol, lauryl alcohol, myristic alcohol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, oleic alcohol, behenyl alcohol, jojoba alcohol, 2-hexadecyl alcohol, 2-octyldodecanol alcohol and isostearyl alcohol.

These amino acid esters can in particular be obtained from natural sources of amino acids. In this case, the amino acids come from hydrolysis of natural vegetable proteins (oats, wheat, soy, palm, coconut) and then necessarily lead to mixtures of amino acids which must then be esterified and then N-acylated. The preparation of such amino acids is more particularly described in the patent application<patcit id="pcit0001" dnum="FR2796550"><text>FR 2 796 550</text></patcit>.

The amino acid ester more particularly preferred for its use in the present invention is isopropyl N-lauroylsarcosinate of formula:         CH₃- (CH₂)₁₀CO-N (CH₃) -CH₂-COO- CH₂- (CH₃)₂.

The amino acid esters preferably used within the meaning of the present invention, as well as their synthesis are described in the patent applications <patcit id="pcit0002" dnum="EP1044676A"><text>EP 1 044 676</text></patcit> and <patcit id="pcit0003" dnum="EP0928608A"><text>EP 0 928 608</text></patcit> from the company AJINOMOTO CO.

In general, the lipophilic amino acid derivative (s) represent from 0.01 to 90% by weight, preferably from 0.1 to 50% by weight and even more preferably from 0.1 to 30% by weight relative to the total weight of the composition.

The compounds of low water solubility within the meaning of the present invention are derivatives of salicylic acid.

In general, the low solubility compound represents from 0.001 to 30% by weight, and preferably from 0.05 to 15% by weight relative to the total weight of the composition.

Within the meaning of the present application, the salicylic acid derivatives of low solubility are the derivatives of formula I ′ or the monovalent, divalent salts or mixtures of these derivatives:<chemistry id="chem0001" num="0001"><img file="EP1269986B1_D0007.tif" /></chemistry>in which<ul id="ul0004" list-style="none" compact="compact"><li>R "₁ represents a hydroxyl radical or an ester of formula         -O-CO-R "₄in which R "₄ is an aliphatic, saturated or unsaturated radical comprising from 1 to 26 carbon atoms, and preferably from 1 to 18 carbon atoms, an amine or thiol function optionally substituted by an alkyl radical comprising from 1 to 18 carbon atoms, and preferably from 1 to 12 carbon atoms,</li><li>R "₂ and R "₃ independently of one another are in one of the positions 3, 4, 5 or 6 on the benzene nucleus and independently of one another represent a hydrogen atom or a radical:         - (O)_not-(CO)_m-R "₅in which n and m, independently of each other, are each an integer equal to 0 or 1, provided that R "₂ and R "₃ are not simultaneously hydrogen atoms,</li><li>and R "₅ represents a hydrogen, a saturated aliphatic radical comprising from 1 to 18 carbon atoms, linear, branched or cyclized, an unsaturated radical comprising from 3 to 18 carbon atoms, carrying one to nine double bonds, conjugated or not, the radicals being able to be substituted with at least one substituent chosen from halogen atoms (fluorine, chlorine, bromine, iodine), trifluoromethyl, hydroxyl radicals in free form or esterified by an acid comprising from 1 to 6 carbon atoms, or free or esterified carboxyl with a lower alcohol comprising from 1 to 6 carbon atoms, an aromatic radical comprising from 6 to 10 carbon atoms.</li></ul>

Preferably, the salicylic acid derivative is such that R "₅ represents a saturated aliphatic radical comprising from 3 to 15 carbon atoms.

Preferably, the salicylic acid derivative is such that R "₁ represents a hydroxyl radical.

Preferably, the salicylic acid derivative is such that R "₃ is in position 5 of the benzene nucleus and R "₂ represents a hydrogen atom.

According to a preferred embodiment of the invention, the salicylic acid derivative is chosen from the n-octanoyl-5-salicylic, n-decanoyl-5-salicylic, n-dodecanoyl-5-salicylic, n-octyl- derivatives. 5-salicylic, n-heptyloxy-5-salicylic, n-heptyloxy-4-salicylic, 5-tert-octylsalicylic, 3-tert-butyl-5-methylsalicylic, 3-tert-butyl-6-methylsalicylic, 3,5- diisopropylsalicylic, 5-butoxysalicylic, 5-octyloxysalicylic, propanoyl-5-salicylic, n-hexadecanoyl-5-salicylic, n-oleoyl-5-salicylic, benzoyl-5-salicylic, their monovalent and divalent salts and their mixtures.

According to another preferred embodiment, the compositions comprise a salt of salicylic acid derivative of formula I 'chosen from among the salts of strontium, calcium, magnesium, barium and manganese. Even more preferably, this salicylic acid derivative salt is chosen from the strontium salt of 5-octanoyl salicylic acid, the calcium salt of 5-octanoyl salicylic acid, the magnesium salt of 5-octanoyl salicylic acid and mixtures thereof.

These derivatives are known in the prior art, in particular the patent application <patcit id="pcit0004" dnum="EP662318A"><text>EP 662,318</text></patcit> relates to the use of such salicylic acid derivatives for manufacturing cosmetic and / or dermatological compositions for the treatment of the body and the face, in particular for the treatment of acne and aging of the skin. Patent applications<patcit id="pcit0005" dnum="EP0662318A"><text>EP 0 662 318</text></patcit>, <patcit id="pcit0006" dnum="EP987011A"><text>EP 987,011</text></patcit> describe processes for the preparation of such salicylic acid derivatives.

Salicylic acid derivatives are of great interest in particular for preventing or repairing the main manifestations of skin aging such as fine lines and wrinkles, disorganization of the “grain” of the skin, modification of the skin tone and loss firmness and tone of the skin. However, the use of these derivatives poses a problem insofar as, when they are introduced as they are into the topical compositions, they do not dissolve and remain in the state of crystals, which makes the use of the composition containing them, ineffective for the treatment of the skin.

Generally, these derivatives are dissolved in lower alcohols such as ethanol or isopropanol or solvents such as octyldodecanol, certain glycols, short chain fatty alcohols (lower than C12). However, these lower alcohols have the drawback of drying and irritating the skin; we therefore prefer to avoid using them in body and / or face care products. In addition, these solubilizers can only be introduced in small quantities under penalty of altering the cosmetic qualities (drying of the skin) and the stability of the compositions containing them.

The concentration of salicylic acid derivatives of the composition according to the present invention is between 0.001 and 15% by weight, preferably between 0.1 and 5% by weight relative to the total weight of the composition. The amount of amino acid esters will depend on the amount of salicylic acid derivatives to be dissolved. It may be between 0.01 and 90% by weight, and preferably between 0.1 and 50% by weight relative to the total weight of the composition.

The composition according to the invention comprising at least one salicylic derivative can be used as a cosmetic or dermatological composition, and in particular for the care, protection, cleaning and / or makeup of keratin materials of human beings (skin, lips, keratin fibers such as hair and eyelashes), and in particular to combat the signs of skin aging and / or to smooth the skin of the face and / or of the body and / or to treat wrinkles and fine lines of the skin and / or to stimulate the epidermal renewal process and / or to depigment and whiten the skin and / or to treat acne and / or to treat skin disorders.

By skin disorders is meant in particular shingles, burns, eczema, demodicosis, skin ulcer, fibrosis, scar control, psoriasis, pruritus, dermatitis, ichthyosis, corns and The warts.

Also, the subject of the invention is also the cosmetic use of the cosmetic composition as defined above for protecting, caring for, cleaning and / or making up the skin and / or mucous membranes and / or fibers keratinous.

The subject of the invention is also a cosmetic treatment method for protecting, caring for, cleaning and / or making up the skin and / or mucous membranes and / or keratin fibers, consisting in applying to the skin and / or mucous membranes and / or keratin fibers, the composition according to the invention.

Another subject of the invention is a cosmetic treatment method for combating the signs of skin aging and / or improving the radiance of the complexion and / or smoothing the skin of the face and / or the body and / or treating wrinkles and fine lines of the skin and / or stimulate the process of epidermal renewal and / or to depigment and / or whiten the skin, consisting in applying to the skin the composition containing a salicylic acid derivative according to the invention.

A subject of the invention is also the use of the composition according to the invention for the manufacture of a dermatological therapeutic composition intended to fight against the signs of skin aging and / or fight against acne and / or fight against disorders skin.

The weight ratio derived from salicylic acid / amino acid ester is preferably from 0.001 / 99.999 to 35/65 and preferably from 0.1 / 99.9 to 30/70.

The cosmetic composition according to the present invention can be in the forms normally used in cosmetics.

It can be in all the forms normally used for topical application, in particular in the form of a hydroalcoholic solution, an oil-in-water or water-in-oil or multiple emulsion, an oily gel, or d a liquid, pasty or solid anhydrous product or in the form of a dispersion in the presence of spherules, these spherules can be polymeric nanoparticles such as nanospheres or nanocapsules or lipid vesicles of ionic or nonionic type. These compositions are prepared according to the usual methods.

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. . It can optionally be applied to the skin or the hair in the form of an aerosol. It can also be in solid form, and for example in the form of a stick.

In a known manner, the cosmetic and dermatological compositions according to the invention can 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, fibers, fillers, filters, pigments, odor absorbers and coloring matter. The amounts of these various adjuvants are those conventionally used in the fields under consideration, and for example from 0.01 to 50% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase, into lipid vesicles and / or into nanoparticles.

Of course, a person skilled in the art will take care to choose these possible additional compounds, active or non-active, and / or their quantity, in such a way that the advantageous properties of the low solubility derivatives are not, or not substantially, altered by the planned addition.

When the composition according to the invention is an emulsion, the proportion of the fatty phase can range from 0.5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The oils, 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 fatty phase or oily phase usually contains at least one oil. As oils which can be used in the composition of the invention, there may be mentioned for example:<ul id="ul0005" list-style="dash" compact="compact"><li>hydrocarbon oils of animal origin, such as perhydrosqualene;</li><li>hydrocarbon-based oils of vegetable origin, such as liquid triglycerides of fatty acids having from 4 to 10 carbon atoms such as triglycerides of heptanoic or octanoic acids or also, for example, sunflower, corn, soybean, squash, grapeseed, sesame, hazelnut, apricot, macadamia, arana, sunflower, castor, avocado, caprylic / capric acid triglycerides such as those sold by the company Stearineries Dubois or those sold under the names Miglyol 810, 812 and 818 by the company Dynamit Nobel, jojoba oil, shea butter oil;</li><li>synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R⁶COOR⁷ and R⁶GOLD⁷ in which R⁶ represents the remainder of a fatty acid containing from 8 to 29 carbon atoms, and R⁷ represents a hydrocarbon chain, branched or not, containing from 3 to 30 carbon atoms, such as for example Purcellin oil, isononyl isononanoate, isopropyl myristate, ethyl-2-hexyl palmitate, octyl-2-dodecyl stearate, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxylated esters such as isostearyl lactate, octylhydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate, heptanoates, octanoates, decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentylglycol diheptanoate and diethylene glycol diisononaoate; and pendaerythritol esters such as pentaerythrityl tetraisostearate;</li><li>linear or branched hydrocarbons, of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petroleum jelly, polydecenes, hydrogenated polyisobutene such as parlameam oil;</li><li>fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, l oleic alcohol or linoleic alcohol;</li><li>alkoxylated and in particular ethoxylated fatty alcohols such as oleth-12;</li><li>partially hydrocarbon and / or silicone fluorinated oils such as those described in the document <patcit id="pcit0007" dnum="JP2295912A"><text>JP-A-2 295912</text></patcit>. As fluorinated oils, mention may also be made of perfluoromethylcyclopentane and perfluoro-1,3-dimethylcyclohexane, sold under the names of "FLUTEC PC1®" and "FLUTEC PC3®" by the company BNFL Fluorochemicals; perfluoro-1,2-dimethylcyclobutane; perfluoralcanes such as dodecafluoropentane and tetradecafluorohexane, sold under the names of “PF 5050®” and “PF 5060®” by the company 3M, or even bromoperfluorooctyle sold under the name “FORALKYL®” by the company Atochem; nanofluoromethoxybutane sold under the name "MSX 4518®" by the company 3M and nanofluoroethoxyisobutane; perfluoromorpholine derivatives, such as 4-trifluoromethyl perfluoromorpholine sold under the name "PF 5052®" by the company 3M;</li><li>silicone oils such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, liquids or pastes at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenylated silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenyl-siloxanes, diphenyl-dimethicones, diphenylmethyldiphenyl trisiloxanes, 2-phenylethyltrimethyl-siloxysilicates, polymethyl-phenyls; and their mixtures.</li></ul>

“Hydrocarbon oil” is understood to mean, in the list of oils mentioned above, any oil mainly comprising carbon and hydrogen atoms, and optionally ester, ether, fluorinated, carboxylic acid and / or alcohol groups.

The other fatty substances which may be present in the oily phase are, for example, fatty acids containing from 8 to 30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and oleic acid; waxes such as lanolin, beeswax, carnauba or candellila wax, paraffin, lignite or microcrystalline waxes, ceresin or ozokerite, synthetic waxes such as polyethylene waxes, waxes from Fischer-Tropsch; gums such as silicone gums (dimethiconol); silicone resins such as trifluroromethyl-C1-4-alkyldimethicone and trifluoropropyldimethicone; and silicone elastomers such as the products marketed under the names “KSG” by the company Shin-Etsu, under the names “Trefil”, “BY29” or “EPSX” by the company Dow Corning or under the names “Gransil” by the Grant Industries.

These fatty substances can be chosen in various ways by a person skilled in the art in order to prepare a composition having the properties, for example of consistency or texture, desired. The emulsions may contain at least one emulsifier chosen from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture.

When the composition is an emulsion, it generally contains at least one emulsifier. The emulsifiers are chosen appropriately according to the emulsion to be obtained water in oil (W / O) or oil in water (O / W).

For O / W emulsions, a nonionic emulsifier can be used, for example, as an emulsifier, such as esters and ethers of sugars such as sucrose stearate, sucrose cocoate, and the mixture of sorbitan stearate and cocoate. of sucrose sold by the company ICI under the name of Arlatone 2121^® ; polyol esters, in particular glycerol or sorbitol, such as glyceryl stearate, polyglyceryl-2 stearate, sorbitan stearate; glycerol ethers; oxyethylenated and / or oxypropylenated ethers such as oxyethylenated ether, oxypropylenated of lauric alcohol with 25 oxyethylenated groups and 25 oxypropylenated groups (CTFA name "PPG-25 laureth-25") and the oxyethylenated ether of the mixture of alcohols C12-C15 fatty having 7 oxyethylenated groups (CTFA name "C12-C15 Pareth-7"); ethylene glycol polymers, such as PEG-100, and mixtures thereof.

For W / O emulsions, the fatty esters of polyol, in particular glycerol or sorbitol, and in particular the isostearic, oleic and ricinoleic polyol esters, such as the mixture of petrolatum and oleate, may be mentioned as emulsifier, for example. polyglyceryl-3, glyceryl isostearate; hydrogenated castor oil and ozokerite, sold under the name PROTEGIN W^® by the company Goldschmidt, sorbitan isostearate, polyglyceryl di-isostearate, polyglyceryl-2 sesqui-isostearate; esters and ethers of oses such as “Methyl glucose dioleate”; fatty esters such as magnesium lanolate; dimethicone copolyols and alkyl-dimethicone copolyols such as Laurylmethicone copolyol sold under the name DOW CORNING 5200 FORMULATION AID by the company Dow Corning and Cetyl dimethicone copolyol sold under the name ABIL EM 90^® by the company Goldschmidt, and their mixtures.

The emulsifiers can be introduced as such or in the form of a mixture with other emulsifiers and / or with other compounds such as fatty alcohols or oils.

As active agents which can be used in the composition of the invention, mention may be made, for example, of moisturizing agents and for example protein hydrolysates and polyols such as glycerin, glycols such as polyethylene glycols, and sugar derivatives; natural extracts; procyannidolic oligomers; vitamins like vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherol), vitamin B5 (panthenol), vitamin B3 (niacinamide); vitamin K; urea; caffeine; depigmenters such as kojic acid and caffeic acid; salicylic acid (for compositions not already containing a salicylic acid derivative); alpha-hydroxy acids such as lactic acid and glycolic acid; retinoids such as carotenoids; sun filters; fillers, pigments, dyes, keratolytic agents, preservatives, antioxidants, perfumes, hydrocortisone; melatonin; extracts of algae, fungi, plants, yeasts, bacteria; hydrolyzed proteins, partially hydrolyzed or non-hydrolyzed, enzymes; anti-bacterial active ingredients for the treatment of oily skin such as 2,4,4'-trichloro-2'-hydroxy diphenyl ether (or triclosan), 3,4,4'-trichlorocarbanilide (or triclocarban), azelaic acid, benzoyl peroxide; matting agents such as fibers; tensing agents; optical brighteners; and their mixtures, such as, for example, the mixture of vitamins (A and C or A + C + E for example).

The active agent (s) may be present in a concentration ranging from 0.01 to 20%, preferably from 0.1 to 10% and better still from 0.5 to 5% of the total weight of the composition.

EXAMPLES

In the following table are presented molecules of low solubility in water within the meaning of the present invention, they are not very soluble in water in particular at room temperature and have a δa&gt; 6J^1/2 cm^-3/2. <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="97mm" /><colspec colnum="2" colname="col2" colwidth="43mm" /><colspec colnum="3" colname="col3" colwidth="27mm" /><thead><row><entry align="center" valign="middle" /><entry align="center" valign="middle">Solubility in water at 25 ° C</entry><entry align="center" valign="middle">ena in J^1/2.cm^-3/2</entry></row></thead><tbody><row><entry align="center" valign="middle">N-Ethoxycarbonyl para aminophenol *</entry><entry morerows="6" align="center" valign="middle">&lt; 1%</entry><entry align="center" valign="middle">16.1</entry></row><row><entry align="center" valign="middle">N-cholesteryloxycarbonyl-para aminophenol *</entry><entry align="center" valign="middle">8.7</entry></row><row><entry align="center">(3beta, 5alpha, 25r) -3-hydroxyspirostan-12-one (Hecogenin acetate) *</entry><entry align="center" valign="middle">6.7</entry></row><row><entry align="center" valign="middle">5-spirosten-3-beta-ol (Diosgenin)</entry><entry align="center" valign="middle">8.6</entry></row><row><entry align="center" valign="middle">n-octanoyl-5 salicylic acid</entry><entry align="center" valign="middle">11.3</entry></row><row><entry align="center" valign="middle">DHEA *</entry><entry align="center" valign="middle">9.9</entry></row><row><entry align="center" valign="middle">2-amino 4-dodecylamino pyrimidine 3-oxide *</entry><entry align="center" valign="middle">8.9</entry></row></tbody></tgroup><tgroup cols="3" rowsep="0"><colspec colnum="1" colname="col1" colwidth="97mm" /><colspec colnum="2" colname="col2" colwidth="43mm" /><colspec colnum="3" colname="col3" colwidth="27mm" /><tbody><row><entry namest="col1" nameend="col3" align="justify">* Examples outside the invention</entry></row></tbody></tgroup></table></tables>

The following examples illustrate the invention without limiting its scope.

<u style="single">1 - Simple solubility</u>

<u style="single">Protocol</u> : the derivatives of low solubility in water are weighed and placed in an airtight pill box. The amount of solvent required is added. The suspension is stirred (magnetic stirring) up to 80 ° C for 1 hour at most.

The dissolution or non-dissolution of the asset, as well as the evolution over time are shown in the table below.

The insolubility of the active ingredient in the solvent is characterized macroscopically by a precipitate or just a cloudy solution, and microscopically by the presence of crystals.

The solvent used is isopropyl N-lauroyl-sarcosinate.<tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="69mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="37mm" /><colspec colnum="4" colname="col4" colwidth="49mm" /><thead><row><entry align="center" valign="middle">Definition</entry><entry align="center" valign="middle">Rate</entry><entry align="center" valign="middle">Solubilization at T0</entry><entry align="center" valign="middle">Stability over time at 25 ° C</entry></row></thead><tbody><row><entry morerows="1" align="center" valign="middle">N-cholesteryloxy-carbonyl- para aminophenol</entry><entry align="center">5%</entry><entry morerows="1" align="center" valign="middle" /><entry align="center" valign="middle">Clear for 7 days</entry></row><row><entry align="center" valign="middle">9%</entry><entry align="center" valign="middle">Clear for 4 days</entry></row><row><entry morerows="3" align="center" valign="middle">N-Ethoxycarbonyl-para aminophenol</entry><entry align="center" valign="middle">5%</entry><entry morerows="3" align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">Clear for 18 days</entry></row><row><entry align="center" valign="middle">20%</entry><entry align="center" valign="middle">Clear for 6 days</entry></row><row><entry align="center" valign="middle">23%</entry><entry align="center" valign="middle">Clear for 6 days</entry></row><row><entry align="center" valign="middle">26%</entry><entry align="center" valign="middle">Clear for 1 day</entry></row><row><entry align="center" valign="middle">DHEA</entry><entry align="center" valign="middle">20%</entry><entry align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">-</entry></row><row><entry align="center" valign="middle">2-amino 4-dodecylamino pyrimidine 3-oxide</entry><entry align="center" valign="middle">1%</entry><entry align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">Clear for 1 day</entry></row><row><entry valign="middle">DIOSGENINE</entry><entry align="center" valign="middle">2%</entry><entry align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">Clear for 3 weeks</entry></row><row><entry valign="middle">HECOGENINE ACETATE</entry><entry align="center" valign="middle">2%</entry><entry align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">Clear for 1 day</entry></row><row><entry morerows="2" align="center" valign="middle">Octanoyl-5-salicylic acid</entry><entry align="center" valign="middle">5%</entry><entry morerows="2" align="center" valign="middle">No recrystallization</entry><entry align="center" valign="middle">Clear for 7 days</entry></row><row><entry align="center" valign="middle">9%</entry><entry align="center" valign="middle">No crystal clear for 4 days</entry></row><row><entry align="center" valign="middle">27%</entry><entry align="center" valign="middle">Crystal clear</entry></row></tbody></tgroup></table></tables>

<u style="single">2 - Emulsification</u>

The solubilization of the active ingredients by the solvents (solubilizers) mentioned above has been verified as an emulsion and thus makes it possible to formulate stable compositions.

The emulsions produced are O / W, with Simulsol 165 as a surfactant (mixture of Glyceryl Searate and PEG-100 Stearate).

The physio-chemical stability of the emulsions is verified by macroscopic, microscopic, pH and viscosity control, after 24 hours and over time. The composition according to the present invention can be in the forms normally used in cosmetics.

<u style="single">Examples of compositions</u>

<tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="16mm" /><colspec colnum="2" colname="col2" colwidth="78mm" /><colspec colnum="3" colname="col3" colwidth="32mm" /><colspec colnum="4" colname="col4" colwidth="25mm" /><thead><row><entry valign="top" /><entry valign="top" /><entry namest="col3" nameend="col4" align="center" valign="top">N-octa-noyl-5 salicylic acid</entry></row><row><entry valign="top">PHASE</entry><entry align="center" valign="middle">CTFA name</entry><entry align="center" valign="top">Compliant example</entry><entry align="center" valign="top">Comparative example</entry></row></thead><tbody><row><entry morerows="3" valign="middle">AT</entry><entry>Conservative</entry><entry align="center">0,2</entry><entry align="center">0,2</entry></row><row><entry>Disodium EDTA</entry><entry align="center">0,15</entry><entry align="center">0,15</entry></row><row><entry>Glycerine</entry><entry align="center">3</entry><entry align="center">3</entry></row><row><entry>Water</entry><entry align="center">qsp100</entry><entry align="center">qsp100</entry></row><row><entry morerows="3" valign="middle">B</entry><entry>Glyceryl stearate and PEG-100 stearate</entry><entry align="center">0,3</entry><entry align="center">0,3</entry></row><row><entry>Cetyl alcohol</entry><entry align="center">0,4</entry><entry align="center">0,4</entry></row><row><entry>Conservative</entry><entry align="center">0,1</entry><entry align="center">0,1</entry></row><row><entry>Triclosan</entry><entry align="center">0,1</entry><entry align="center">0,1</entry></row><row><entry morerows="3" valign="middle">VS</entry><entry>N-cholesterylcarbony 1 paraaminophenol</entry><entry align="center">-</entry><entry align="center">-</entry></row><row><entry>N-ethoxycarbonyl-paraamino-phenol</entry><entry align="center">-</entry><entry align="center">-</entry></row><row><entry>5-n-octanoyl salicylic acid</entry><entry align="center">1</entry><entry align="center">1</entry></row><row><entry>Isopropyl Lauroylsarcosinate</entry><entry align="center">10</entry><entry align="center">-</entry></row><row><entry morerows="1" valign="middle">D</entry><entry>Crosslinked polymer (acrylates / C₁₀-VS₃₀ alkyl acrylate)</entry><entry align="center">0,5</entry><entry align="center">0,5</entry></row><row><entry>Cyclohexasiloxane</entry><entry align="center">5</entry><entry align="center">5</entry></row><row><entry valign="middle">E</entry><entry>Water</entry><entry align="center">10</entry><entry align="center">10</entry></row><row><entry valign="middle" /><entry>Alcohol</entry><entry align="center">5</entry><entry align="center">5</entry></row><row><entry valign="middle">F</entry><entry>Polyacrylamide and isoparaffin C₁₃-VS₁₄ and laureth-7</entry><entry align="center">1</entry><entry align="center">1</entry></row><row><entry morerows="1" valign="middle">G</entry><entry>triethanolamine</entry><entry align="center">1,03</entry><entry align="center">1,03</entry></row><row><entry>Water</entry><entry align="center">7</entry><entry align="center">7</entry></row></tbody></tgroup></table></tables>

<u style="single">PROCEDURE:</u>

<u style="single">Phase A</u>

The mixture is heated to 85 ° C. Agitation is carried out to dissolve the preservatives. Then the temperature is lowered to 75 ° C to make the emulsion.

<u style="single">Phase B</u>

The mixture is heated to 75 ° C. and homogenized until complete dissolution. Production of the emulsion: B is poured into A at 75 ° C. with stirring for 15 min.

<u style="single">Phase C</u>

Homogenize until complete dissolution at 30 ° C and add to the emulsion (A + B) at 60 ° C.

<u style="single">Phase D</u>

Disperse at room temperature, and add to the emulsion (A + B + C) at 60 ° C. We homogenize.

<u style="single">Phases E, F and G</u>

They are prepared at room temperature, then they are added to the emulsion (A + B + C + D) at 40 ° C, and homogenization is carried out with stirring. The emulsion is allowed to cool to 25 ° C.

It has been shown that the solubilization of derivatives of low solubility with amino acid esters is well achievable in emulsion in order to confirm that it is possible to formulate the stable cosmetic compositions containing such derivatives.

The emulsions produced above are oils in water with Simulsol 165 sold by the company SEPPIC as a surfactant, Simulsol 165 being a mixture of glyceryl stearate and PEG-100 stearate.

The physicochemical stability of the emulsions is checked by macroscopic, microscopic, pH and viscosity control after 24 hours.<tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="54mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><colspec colnum="3" colname="col3" colwidth="57mm" /><thead><row><entry valign="top" /><entry align="center" valign="top">With 10% isopropyl N-lauroylsarcosinate (compliant)</entry><entry align="center" valign="top">Without isopropyl N-lauroylsarcosinate</entry></row></thead><tbody><row><entry>1% N-octanoyl-5 salicylic acid</entry><entry>Example Emulsion without crystals, it remains compliant up to 2 months at 4/25 and 45 ° C</entry><entry>Comparative example Fine emulsion with crystals from T 24 hours</entry></row></tbody></tgroup></table></tables>

The compositions in accordance with the invention do not contain crystals and are stable over time and in temperature, while the compositions of the comparative examples exhibit crystals as early as 24 hours after their preparation.