FR3013982B1

FR3013982B1 - COMBINATION OF TWO COMPOUNDS FROM FATTY ACIDS

Info

Publication number: FR3013982B1
Application number: FR1362054A
Authority: FR
Inventors: Alexandra Fregonese; Alexandre Eveillard
Original assignee: Innovi SAS
Current assignee: Innovi SAS
Priority date: 2013-12-04
Filing date: 2013-12-04
Publication date: 2019-06-07
Anticipated expiration: 2033-12-04
Also published as: WO2015082857A1; FR3013982A1

Abstract

L'invention concerne une combinaison de deux composés issus d'acides gras et les utilisations cosmétiques et dermatologiques de cette combinaison, cette dernière étant une combinaison d'au moins un composé (a) issu de la condensation d'au moins un acide gras avec une alcanolamine, et d'au moins un composé (b) hydrosoluble, de formule RCOR' où R représente une chaine hydrocarbonée ayant de 3 à 35 atomes de carbone, et R' représente un reste d'acide aminé ou d'un sel d'acide aminé, chacun de (a) et (b) étant présent en une proportion d'au moins 1% en masse par rapport à la masse de la combinaison.The invention relates to a combination of two compounds derived from fatty acids and the cosmetic and dermatological uses of this combination, the latter being a combination of at least one compound (a) derived from the condensation of at least one fatty acid with an alkanolamine, and at least one water-soluble compound (b) of formula RCOR 'where R represents a hydrocarbon chain having from 3 to 35 carbon atoms, and R' represents an amino acid residue or a salt thereof. amino acid, each of (a) and (b) being present in a proportion of at least 1% by weight relative to the mass of the combination.

Description

The present invention relates to a combination of at least two compounds derived from fatty acids and its use in cosmetology,> pharmaceutical, especially in dermatology, in particular to facilitate the transcutaneous penetration of molecules.

It also relates to a cosmetic, pharmaceutical, especially dermatological composition comprising such a combination and intended to promote the bioavailability of molecules, especially those active at the cutaneous level. A combination of the invention allows and / or promotes the penetration and / or action of active molecules, including high molecular weight molecules and / or few available on their target site, such as the middle layers of the skin, especially in order to reach the basal layers and / or the living cells of the epidermis. Surprisingly, it ensures homogeneous diffusion and also allows them to be maintained in the medial layers, such as the lower layers of the epidermis and the upper layers of the dermis of the various epithelia of the human body, such as the cutaneous epithelium. the oral cavity, the digestive tract, the vaginal cavity, ...

A combination of the invention makes it possible to reduce the loss of said one or more molecules, whether contained in the combination or applied before or after the combination, through the various cell layers during skin penetration, in particular but not exclusively , through the stratum corneum.

Human skin is made up of three main layers> superimposed and communicating, from the deepest to the most superficial: the hypodermis, the dermis and the epidermis separated by the dermal-epidermal junction. The hypodermis is the deepest and thickest layer of the skin. The hypodermis is a fibro-adipose tissue essentially composed of> adipocytes, cells specialized in the storage of lipids, grouped into lobules and separated by connective tissue. It plays the role of thermal insulation, energy reserve and protection against shocks.

The dermis is an innervated and vascularized connective tissue of mesenchymal origin consisting mainly of water and protein fibers embedded in a reticular gel of mucopolysaccharides and proteoglycans. It plays a major role in the nutrition, support and protection of the epidermis and cutaneous appendages, but is also involved in thermoregulation, healing and defense against pathogens thanks to the presence of immune cells, such as cells dendritic dermis, macrophages and T lymphocytes). The superficial part of the dermis invaginates at the junction with the epidermis in the form of dermal papillae, increasing the surface of contact with the epidermis and allowing a better adhesion between these two layers. The dermal papillae contain the nerve fibers, which can penetrate the basal lamina to innervate the epidermis or be connected to real nervous corpuscles in the dermis acting as tactile mechanoreceptors. The dermal papillae are also composed of blood vessels, which do not enter the epidermis. The main cells of the dermis are the fibroblasts that will synthesize two types of protein fibers: collagen fibers and elastin fibers, constituents of the extracellular matrix. The vast majority of fibers present in the dermis are collagen fibers (> 90%), essentially of type 1 and 3, responsible for the mechanical strength of the skin, whereas elastin fibers participate in its elasticity. . At the level of the deeper dermis (reticular dermis) these fibers will be organized parallel to the surface of the skin. Nerve corpuscles, receptors> of pressure variations, but also of blood vessels and cutaneous appendages are also found at this level: the hair follicles, closely associated with the sebaceous glands and the sweat glands. The epidermis is a pluristratified epithelium consisting of four superimposed layers each formed of one or more cellular layers. > 1) The basal or germinal layer is a monolayer of proliferative cells attached to the dermis by the dermal-epidermal junction. The basal keratinocytes are cubic in shape, with a large nucleus and abundant melanosomes. The keratinocytes of the basal layer are the only ones to be mitotically active and relatively undifferentiated. They ensure the renewal of epithelial cells of the epidermis. 2) The spiny layer is composed of 5 to 10 cellular layers in humans. It owes its name to the presence of many "spines" visible in optical microscopy which are in fact desmosomes, from which converge numerous bundles of intermediate filaments, ensuring cohesion> intercellular mechanics. 3) The granular layer is the last layer of living cells of the epidermis. It consists of 2 to 3 cell layers in humans, flattened with a nucleus perpendicular to the dermal-epidermal junction. Tubulo-vesicular structures called lamellar bodies or> keratinosomes are also present in the cytoplasm of granular keratinocytes. They play a major role in the establishment of the epidermal barrier function by discharging their protein and lipid content by exocytosis at the granular layer / horny layer interface leading to the formation of an intercorneocyte cement. 4) The stratum corneum consists of 25 to 30 layers of dead and anucleate cells: the corneocytes. The cell organelles and the nucleus are degraded during the transformation of granular keratinocytes into corneocytes, the cornification, the cytoplasm giving way to a fibrous matrix of keratin and filaggrin. The cytoplasmic membrane is replaced by> a rigid and insoluble shell, the horny envelope. The deepest part of the horny layer called stratum compactum consists of cohesive cells while the most superficial part, the stratum disjonctum, is composed of disco-adhesive cells.

The stratum corneum is generally modeled by the simple model of the brick wall proposed by Elias with intercorneocyte lipids as cement. A more elaborate model was made by Forslind in 1994. This model of "domain mosaic model" considers the supramolecular organization of the lipid matrix. The majority of lipids are in the orthorhombic or hexagonal phase. In this crystalline state, the lipid acyl chains are predominantly in the trans configuration. In addition, some of the lipids would be in a more disordered conformation. These more fluid regions could represent the path taken by hydrophobic molecules to diffuse through the stratum corneum. In addition, in these regions, lipid structural changes induced by permeability increasing products could occur without altering the more orderly phase structures. This is the first model suggesting the presence of a fluid phase in the stratum corneum.

The present invention provides a solution for promoting the penetration of molecules, especially active molecules, through the epidermis to reach the lower layers of the epidermis and the upper layers of the dermis.

The present invention provides a solution to the toxicity of certain substances by limiting their diffusion to a specific area, the target area.

Thus, the invention relates to a combination of at least one compound (a) derived from the condensation of at least one fatty acid with an alkanolamine, and> of at least one water-soluble compound (b), of formula RCOR 'where R represents a hydrocarbon chain having from 3 to 35 carbon atoms, and R 'represents a hydrophilic group, organic or inorganic, ionic or not, capable of conferring on the compound (b) its water-solubility, each of (a) and (b) being present in a proportion of at least 1% by weight with respect to the mass of the combination.

Compound (a) can be obtained from all fatty acids. Saturated fatty acids are however preferred. By way of example, mention may be made of:

Among the saturated fatty acids, the following acids:> formic acid (or methanoic acid) C1: 0 acetic acid (or ethanoic acid) C2: 0 propionic acid (or propanoic acid) C3: 0 butyric acid (or butanoic acid) C4: 0 valeric acid (or pentanoic acid) C5: 0> caproic acid (or hexanoic acid) C6: 0 enanthic acid (or heptanoic acid) C7: 0 caprylic acid (or octanoic acid) C8: 0 pelargonic acid (or nonanoic acid) C9 : 0 capric acid (or decanoic acid) C10: 0> undecylic acid (or undecanoic acid) C11: 0 lauric acid (or dodecanoic acid) C12: 0 tridecylic acid (or tridecanoic acid) C13: 0 myristic acid (or tetradecanoic acid) C14: 0 pentadecyl acid (or pentadecanoic acid) C15: 0> palmitic acid (or hexadecanoic acid) C16: 0 margaric acid (or heptadecanoic acid) C17: 0 stearic acid (or octodecanoic acid) C18: 0 nonadecyl acid (or nonadecanoic acid) ) C19: 0 arachic acid idic (or eicosanoic acid) C20: 0> behenic acid (or docosanoic acid) C22: 0 lignoceric acid (or tetracosanoic acid) C24: 0 cerotic acid (or hexacosanoic acid) C26: 0 montanic acid (or octacosanoic acid) C28: 0 melissic acid (or triacontanoic acid) C30: 0 laceroic acid (or dotriacontanoic acid C32: 0> among the monounsaturated fatty acids, the following acids: palmitoleic acid (or 9Z-hexadecenoic acid) C16: 1 ω-7 oleic acid ( or 9Z-octadecenoic acid) C18: 1 ω-9 erucic acid (or 13Z-docosaenoic acid) C22: 1 ω-9 nervonic acid (or 15Z-tetracosaenoic acid) C24: 1 ω-9> among polyunsaturated fatty acids the following acids: linoleic acid (or 9Z, 12Z-octadecadienoic acid) C18: 2 ω-6 α-linolenic acid (or 9Z, 12Z, 15Z-octadecatrienoic acid) C18: 3 ω-3 γ-linolenic acid (or acid 6Z, 9Z, 12Z-octadecatrienoic) C18: 3 ω-6 Dihomo-y-linolenic acid (or 8Z, 11Z, 14Z-eicosatriate acid) no.) C20: 3 ω-6> arachidonic acid (or 5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid) C20: 4 ω-6 eicosapentaenoic acid (or 5Z, 8Z, 11Z, 14Z, 17Z-eicosapentaenoic acid), C20: 5 ω-3 docosahexaenoic acid (or 4Z, 7Z, 1 OZ, 13Z, 16Z, 19Z-docosahexaenoic acid) C22: 6 ω-3. In one variant of the invention, the fatty acid or acids condensed with the alkanolamine may be those of a mixture of fatty acids of an oil and / or a butter.

Among the preferred oils, mention may be made of the following: Laurel bay oil, comprising:> saturated fatty acids (28.63%) of which lauric acid (11.61%), palmitic acid (14.87%), acid stearic acid (1.55%), myristic acid (0.60%) monounsaturated fatty acids: oleic acid (40.32%) essential polyunsaturated fatty acids: linoleic acid (23.80%), linolenic acid (0.83%) %). > Palm oil, obtained from the pulp of the fruit of the palm Elaeis guineensis, and comprising: saturated fatty acids (48.8%) including palmitic acid (44.0%), stearic acid (4.4%) monosaccharide AG unsaturated: oleic acid (38.4%)> polyunsaturated essential fatty acids: linoleic acid (omega 6) (9.4%) Palm kernel oil, derived from the seed of the palm fruit Elaeis guineensis, and including: AG saturated (82%) of which lauric acid (48.2%), myristic acid (16.2%), palmitic acid (8.4%), capric acid (3.4%), caprylic acid (3.3%), stearic acid (2.5%) AG monounsaturated: oleic acid (15.3%) AG polyunsaturated: linoleic acid (2.3%)

In a list of preferred butters according to the invention, in particular because of their high saturated fatty acid content, the following butters are found: Murumuru butter, derived from the pressure of the seed of the tree

Astrocaryum murumuru, and comprising: saturated fatty acids (88.6%) including lauric acid (49.8%), myristic acid (23.5%), palmitic acid (5.8%), stearic acid (3.4%) , capric acid (2.1%), caprylic acid (4.0%)> mono-unsaturated fatty acids: oleic acid (omega 9) (7.1%) essential polyunsaturated fatty acids: linoleic acid (omega 6) (3) , 1%)

Tucuma butter. obtained from an Amazonian palm tree, Astrocaryum tucuma, and comprising: saturated fatty acids: lauric acid (46.28%), myristic acid (23.29%), stearic acid (5.54%), palmitic acid (5.99%) AG monounsaturated: oleic acid (omega-9) (10.60%) essential polyunsaturated fatty acids: linoleic acid (omega-6) (3.15%)

Cocoa butter, obtained from the cold pressing of the cocoa bean (Theobroma cacao), and comprising:> saturated fatty acids (59.2%) including stearic acid (33.0%), palmitic acid (26.2%) ) Mono-unsaturated AG: oleic acid (33.2%) essential polyunsaturated AG: linoleic acid (omega 6) (3.3%)

Cupuaçu butter, derived from the seed of a tree, Theobroma I grandifolium, and comprising: saturated fatty acids (49%) including stearic acid (30.8%), arachidic acid (10.7%), palmitic acid ( 7.5%) monounsaturated fatty acids: oleic acid (omega-9) (41.7%) polyunsaturated essential fatty acids: linoleic acid (omega-6) (5.0%)> Sal butter or tallow Borneo, obtained from the fruit cores of Shorea robusta, and including: saturated (55.6%) AG including stearic acid (42.7%), palmitic acid (12.9%) mono-unsaturated AG: oleic acid (omega) 9) (37.30%) Polyunsaturated essential fatty acids: linoleic acid (omega-6) (2.1%)> Kokum butter, also called Gurgi nut fat, derived from the seed of Garcinia indica, and comprising: Saturated fatty acids (51.83%) including palmitic acid (17.55%), stearic acid (34.28%) monounsaturated fatty acid: oleic acid (omega-9) (34.96%)> polyunsaturated essential fatty acids : linoleic acid (omega-6) (4.08%)

Kpangnan's butter. also called golden karité or Kanya butter, derived from the seed of Pentadesma butyracea, and comprising: saturated fatty acids (47.7%) including stearic acid (40.00%), palmitic acid (7.70%)> mono-fatty acid unsaturated: oleic acid (42.30%) essential polyunsaturated fatty acids: linoleic acid (omega 6) (4.40%)

Mango butter, obtained by cold pressing of the mango kernel kernel, and comprising: saturated fatty acids (54.56%) including iso-stearic acid (36.66%), palmitic acid (14.96%) %) Monounsaturated AG: oleic acid (omega-9) (39.87%) essential polyunsaturated AG: linoleic acid (omega-6) (4.56%)

In this list, the proportions of AG are expressed as AG mass per 100 g of butter. The alkanolamine leading to the compound (s) (a) corresponds to the formula N (H) n [(CH 2) mOH] p [(CH 2) mOH] where n is equal to 0, 1 or 2 , p and p ', which may be identical or different, are equal to 1.2 or 3, with n + p + p' = 3, and m and m ', which may be identical or different, vary from 1 to 10, preferably from 1 to 5. Advantageously, the alkanolamine is chosen from mono-, di- and tri-ethanolamine. More preferably, it is monethanolamine.

Thus, according to an advantageous combination, the compound or compounds (a) are chosen from lauric monoethanolamide and any mixture of lauric monoethanolamide with another compound (a) derived from the condensation of a fatty acid or a mixture of acids. with an> alkanolamine.

Compound (b) is a water-soluble compound of formula RCOR '.

In this formula, R represents a hydrocarbon chain of a fatty acid, said fatty acid may be chosen from the group of fatty acids described above in the context of the definition of compound (a), said fatty acid being able to be identical or different. Thus, R is preferably a> hydrocarbon chain having from 3 to 35 carbon atoms. This hydrocarbon chain may be saturated or unsaturated, it is preferably non-cyclic.

In the formula RCOR ', R' represents a hydrophilic group, organic or inorganic, ionic or not, capable of conferring on the compound (b) its water solubility. In a preferred variant of the invention, R may represent an amino acid residue or its salt. Amino acid includes standard amino acids (or protein) and non-standard amino acids such as pyramutamic acid. By amino acid residue is meant the remaining residue of the amino acid covalently bound to the carbon atom of the formula RCOR '. A preferred compound (b) of the invention is Olivoyl Potassium-PCA. This compound is commercially available, it can also be obtained by condensation between a mixture of fatty acids of olive oil with pyroglutamate, potassium for example. Pyrogutamic acid (or pyrrolidone carboxylic acid, also known as PCA), or its salt, is a physiological molecule present in many tissues. Although 97% of total PCA is found in the epidermis, L-pyrrolidone carboxylic acid is found in many organs such as the brain, liver, and in biological fluids. L-PCA is a biochemical intermediate of compounds found abundantly in collagen: proline and> hydroxyproline. This information is particularly interesting when it is known that, together, proline and hydroxyproline represent approximately 21% of the constituent amino acids of collagen, the rest being mainly composed of glycine (35%) and alanine (11%). The abundance of the proline / hydroxyproline combination is responsible for the rigidity and stability of the collagen.

In the body and more particularly at the cutaneous level, the pyrogiutamic acid is an excellent agent of differentiation of the epidermis favoring the synthesis of the epidermal lipids and the maturation of the filaggrine. Present in large quantities in filaggrin (27%) then in the> natural moisturizing factor (NMF) (12%), L-PCA is therefore a moisturizing element of choice. Many studies have attributed this action to its power, hygroscopic. Since hydration is vital for maintaining the elasticity and flexibility of the stratum corneum, the action of L-PCA is essential.

A combination of the invention is prepared by simple mixing of the various compounds (a) and (b) in an indifferent order, given their nature and therefore their presentation, preferably heating to the fusion of the compounds is This heating is advantageously carried out after mixing the compounds, but alternatively, each compound (a) and (b) can be first melted and then mixed, whether or not the heating is continued.

According to the invention, the proportion of the compound (s) varies from 1 to 99% and that of the compound (s) varies from 1 to 99%, these proportions being expressed in mass relative to the mass of the compound. combination.

In an advantageous variant of the invention, the compound (a) is lauric monoethanolamide, resulting from a condensation of lauric acid with monoethanolamine, or the monoethanolamide of coconut oil fatty acids, resulting from a 5 condensation of a mixture of coconut oil fatty acid, in which lauric acid is predominant, with monoethanolamine.

In an advantageous variant of the invention, the compound (b) is potassium Olivoyl-PCA, resulting from the condensation of a mixture of fatty acids of olive oil with the potassium salt of pyrogiutamic acid. Advantageously, the coconut oil fatty acid monoethanolamide is present in a proportion ranging from 15 to 85%, preferably from 15 to 60%, and / or potassium Olivoyl-PCA in a proportion varying from 15 to 85%, preferably 40 to 85%, the proportions being expressed by weight relative to the weight of the combination. It also relates to a cosmetic, pharmaceutical or cosmetic composition. dermatological tattoo for topical use, comprising a combination of the invention, and excipients acceptable from a cosmetic, pharmaceutical or dermatological point of view, and optionally one or more cosmetic, pharmaceutical or dermatological active ingredients. The present invention relates to a mixture of ίθ molecules with biovector properties for all molecules whose cosmetic, dermatological and / or pharmaceutical interest is located on the middle layers of the skin.

The present invention will be able to be associated with all the substances naterally bioavailable or not, intended to act on the cells of the epidermis and / or the basal lamina in order to stimulate them, to protect them, and / or to inhibit them. . Particularly, and not exclusively, are the Langerhans cells, fibroblasts, melanocytes, keratinocytes and extracellular matrix.

The present invention relates to a combination of two compounds defined above, which allows and / or promotes the percutaneous penetration of> active molecules. The cutaneous penetration of active molecules depends in particular on the molecular weight of the molecule, its hydrophilicity or lipophilicity, its melting point, its pH and its ionization, its concentration. High molecular weight molecules have little or no skin penetration (hyaluronic acid, collagen,> vitamin D, ...). The present invention makes it possible to overcome, in part, the constraints related to the physicochemical characteristics of the molecule by transporting it on its site of action.

A combination of the invention, thanks to its biovector capabilities can act on skin hydration by promoting the penetration and diffusion> for example of hygroscopic molecules often difficult to penetrate due in particular to the high molecular weight of said substances.

A good cutaneous hydration is essential to give the skin suppleness, elasticity and a certain impermeability. The dermis is the main water reservoir of the skin, thanks to proteoglycans such as hyaluronic acid, molecules with exceptional hygroscopic properties. Its water content is 80%. From the basal layer to the granular layer, the human epidermis contains 65 to 70% of water but this rate decreases in the stratum compactum where it is only 40%. The upper layer of the stratum corneum (stratum disjunctum) contains only 15%> of water. This gradient is due to the disappearance of constituents with the ability to retain water: nucleic acids, proteins and phospholipids. This gradient of decreasing hydration allows the free water of the dermis to diffuse from the deepest layers to the most superficial ones. The maintenance of a good cutaneous hydration, passes by:> - the diminution of the evaporation, and - the increase of the fixation of the water during its passage through the stratum corneum. The addition of the invention to a cosmetic, dermatological and / or pharmaceutical formulation facilitates the penetration and fixation of hygroscopic molecules which fix the water and contributes to the reduction of evaporation.

The present invention, thanks to its biovector capabilities can act on the skin defenses by promoting the diffusion of eg Langerhans cells activating molecules.

Langerhans cells located in the dermis constitute the immune system of the skin. As the skin represents the most important contact surface with the potentially pathogenic elements of the external environment (viruses, bacteria, toxic, etc.), it is essential to have a high-performance defense system. However, since these cells are embedded in the epidermis, it will be advantageous to associate with all types of active agents, the present invention in order to be able to cross the stratum corneum and reach the Langerhans cells in order to stimulate them and / or to initiate their action.

The present invention, thanks to its biovector capabilities can act on the extracellular matrix of the dermis by acting for example on fibroblasts.

Fibroblasts are the main cells of the dermis. They specialize in the synthesis of two types of protein fibers: collagen fibers and elastin fibers constituting the extracellular matrix. These fibers give the skin its resistance to tension and traction as well as its elastic properties. Their stimulation requires that the present invention dispenses with the relative impermeability of the stratum corneum or stratum corneum.

The present invention, thanks to its biovector capabilities can act on cutaneous pigmentation by acting for example on melanocytes. > The pigmentation of the skin is a complex process that starts with the synthesis of melanin by melanocytes. In humans, the entire population of melanocytes is localized in the hair follicles and in the basal layer of the epidermis. In addition to the aesthetic side, the main role of melanins is to protect the skin against the harmful effects of UV rays. The association of molecules stimulating or inhibiting the production of melanin with the invention will increase the bioavailability of the associated substances and limit the loss of active ingredients through the various cell layers. The present invention may advantageously be associated with all types of antioxidant molecules in order to protect the extracellular matrix and / or the membranes of epidermal and / or basal cells.

The present invention, thanks to its biovector capabilities can also act on an anesthetic effect. The ability of the invention to reach the dermal papillae which contain the nerve fibers and which penetrate the basal lamina to innervate the epidermis (binding to nervous corpuscles in the dermis playing the role of tactile mechanoreceptors) is of interest in cosmetics , in particular, but not exclusively, in the context of hair removal or tattoos and / or aesthetic medicine. The invention is also of interest for drug forms such as patches by improving their efficacy and / or speed of action, whether or not this list is limiting, anesthetics and / or topical 0 cutaneous used in cosmetic surgery.

A combination of the invention is also intended to convey active molecules, in order to correct cutaneous pathologies whose origin lies between the lower layers of the epidermis and the upper layers of the dermis.

Many epidermal pathologies are related to defects in the composition of the lipid shell. Defects in ceramide expression and disruption of lamellar organization have been observed in psoriasis and atopic dermatitis (Di Nardo, 1998, Ghadially et al., 1995, Madison, 2003). The present invention, thanks to its biovector capabilities, makes it possible to restructure defects in the composition of the lipidic envelope. The present invention is now illustrated, but not limited to, by the following examples in support of FIGS. 1-5, in which:

Figures 1 and 2 are photographs illustrating the ex vivo efficacy of a combination of the invention on the diffusion of an active molecule, a coloring agent. Figure 3 is a diagram showing the cutaneous penetration rate (in arbitrary unit gain, ua) of a combination of the invention, as a function of the proportions of ingredients (a) and (b).

Figures 4 and 5 correspond to photographs illustrating the in vivo efficacy of a combination of the invention on the diffusion of an active molecule, a dyeing agent.

Example 1 Preparation of a compound (b)

Potassium Olivoyl-PCA is a mixture of fatty acids of olive oil condensed with the potassium salt of pyroglutamic acid. PCA is generally obtained from wheat gluten and then partially hydrolysed wheat proteins. It is thus obtained olive oil fatty acids which are associated with a hydrophilic part. According to the invention, Potassium Olivoyl-PCA is a preferred compound (b), but of course it is not restricted thereto, and any water-soluble fatty acid derivative is suitable. Thus, all the methods making it possible to render a fatty acid, a mixture of fatty acids, an oil, a butter, water soluble are concerned by the invention. Without being exhaustive, we can cite the following reactions: - Saponification:

This reaction consists in the hydrolysis of fatty acids in an alkaline medium by a base: potash (KOH) or sodium hydroxide (NaOH). Saponification is a slow but total reaction. To accelerate the reaction it can be carried out at temperatures between 80 and 100 ° C and with constant stirring. The saponification of fatty substances produces glycerol and a mixture of carboxylates (of> sodium or potassium) which constitutes the soap. - Sulfation:

Sulfation is the act of attaching one or more sulfate group (s) to a molecule. Sulphate is a hydrophilic (negatively charged) anionic group (which has a good affinity for>water); the sulphation of the oil will give it a hydrophilic part, which makes it soluble in water.

EXAMPLE 2 Preparation of Combinations of the Invention Various combinations of the invention are prepared from (a) lauric monoethanolamide and (b) potassium Olivoyl-PCA, the proportions of which in mass relative to the total mass of the combination, ranged from 0-75% for (a) and from 25-100% for (b).

The constitution of the prepared combinations is specified in the following Table 1:

Table 1

Each of these compositions was prepared according to the following protocol for a total mass of 100 g: - the different compounds (a) and (b) are weighed in a beaker of 250 ml as indicated in the table above; the mixture is heated until the complete dissolution of the compounds is achieved; - The mixture is homogenized using a mixer (different types of mixers can be used: spatula, vortex, propeller, ...) - and let the mixture cool.

Efficiency on the tests carried out (described in the following examples) was observed on all the combinations combining the 2 compounds, as soon as the compound (a) and the compound (b) are present in a proportion of at least 1% and at least 25%, this proportion being expressed in mass relative to the mass of the combination, that is to say for the samples B, C, D, E, F, G, H, I, J , K, L, M, N, O, P and Q. The optimal efficiency was observed with sample I (35% lauric monoethanolamide and 65% Olivoyl potassium-PCA).

Example 3 Ex Vivo Efficacy of a Combination of the Invention on the Diffusion of Molecules

A skin penetration test was performed with combination I of Table 1 above, as follows:

Application of combination I (Figure 2) or not, as a control (Figure 1) to the surface of the skin of a pork ear. Depositing a drop of red dye (eosin) on the treated skin area (Figure 2) or not (Figure 1) and keeping in contact for one minute (Figures 1A and 2A).

Wipe the skin is wiped without rinsing using paper towels (Figures 1B and 2B). Achievement of a histological section of 50 pm using a vibratome on the central part of the deposit zone of the dye drop. The section is then observed under a microscope (× 100 magnification) to visualize the level of penetration and / or the bioavailability of the product at the tissue level (FIGS. 1C and 2C).

It is observed that, in the area of skin not treated with combination I, the dye penetrated superficially into the skin (FIG. 1C) whereas on the area of skin treated, the application facilitated the homogeneous diffusion of the active agent over the skin. medial layers of the skin (Figure 2C).

Example 4 Influence of the proportions of the compounds (a) and (b) in a combination of the invention on the diffusion of molecules, ex vivo

The test performed previously on pig's ear was conducted with the various combinations A to Q of the invention described in Table 1 above.

The test described in Example 3 was carried out for each of the AQ combinations. The intensity of penetration was evaluated on a scale of 0 to 10. 0 being the total absence penetration and the optimal penetration obtained.

The results of these tests are shown in Figure 3.

Penetration level 10 corresponds to a deep penetration at the level of the layers of the dermis. The penetration levels 9 to 5 correspond to a penetration located respectively from the upper layers of the dermis to the deep layers of the epidermis. Given that the level of penetration 8 is the only one that allows to completely cover all of this area (deep layer of the epidermis and upper layer of the dermis). Level 4 corresponds only to a penetration on the middle layers of the epidermis. For the purposes of the invention, the combinations correspond to those for penetrating the molecules between the deep layers of the epidermis and the upper layers of the dermis.

Efficiency was observed for the D, E, F, G, H, I, J, K, L, M, NO and P combinations. Optimal efficacy was observed with Sample I.

Example 5 In Vivo Effectiveness of the Invention on Molecular Diffusion

A skin penetration test was performed with combination I as follows on human skin.

In order to demonstrate the effectiveness of the invention on the diffusion of active ingredients through the different layers of the skin, the combination I was stained with a blue dye. The colored combination I (Figure 5A) or the dye alone (Figure 5A) were applied to the skin. One minute after the application the products were wiped without rinsing. The dye penetrated slightly into the skin in the control case (FIG. 4B) whereas it not only diffused on the surface of the skin with the combination of the invention but also penetrated more significantly (intensity of the color) (Figure 5B). In both cases, rinsing with detergent and water was performed for 10 seconds. In the case control, the dye was completely leached while with the combination of the invention, the color remains in the middle layers of the skin.

Claims

A combination of at least one compound (a) derived from the condensation of at least one fatty acid with an alkanolamine, and at least one compound (b) hydrosubstituted, of formula RCOR 'wherein R represents a hydrocarbon chain having from 3 to 35 carbon atoms, and R 'represents an amino acid residue or an amino acid salt, capable of conferring on the compound (b) its water-solubility, each of (a) and (b) being present in a proportion of at least 1% by weight relative to the mass of the combination.

2. Combination according to claim 1, characterized in that the compound or compounds (a) are derived from the condensation of at least one fatty acid chosen from saturated fatty acids, monounsaturated and polyunsaturated fatty acids and mixtures thereof. with an alkanolamine,

3. Combination according to claim 1 or 2, characterized in that the compound or compounds (a) are derived from the condensation of at least one fatty acid with monoethanolamine,

4. Combination according to any one of claims 1 to 3, characterized in that R represents the hydrocarbon chain of a fatty acid selected from saturated fatty acids, monounsaturated and polyunsaturated fatty acids and mixtures thereof.

5. Combination according to any one of claims 1 to 4, characterized in that the compound (a) is ethanolamide of coconut fatty acids.

6. Combination according to any one of claims 1 to 5, characterized in that the compound (b) is derived from the condensation of a mixture of fatty acids of olive oil and a salt of the pyrogamutamic acid.

Combination according to any one of Claims 1 to 6, characterized in that the proportion of compound (a) and / or that of compound (b) varies from 1 to 99% by weight relative to the mass of the combination. .

8. Combination according to any one of claims 1 to 7, characterized in that the proportion of the compound (a) and / or that of the compound (b) vary from 15 to 85% relative to the mass of the combination.

9. Combination according to any one of claims 5 and 6 to 8, characterized in that the coconut fatty acid ethanolamide is present in a proportion varying from 15 to 60% by weight relative to the mass of the coconut oil. combination.

10. Combination according to any one of claims 1 to 8, characterized in that the compound (b) is derived from the condensation of a mixture of fatty acids of olive oil and a salt of the Pyrogluamic acid is present in a proportion ranging from 40 to 85% by weight relative to the weight of the combination.

11. Composition comprising a combination according to any one of claims 1 to 10 and at least one active molecule.

Cosmetic, pharmaceutical or dermatological composition for topical use, a combination according to any one of Claims 1 to 10, and excipients which are acceptable from the cosmetic, pharmaceutical or dermatological point of view, and at least one molecule which is active from the point of view of the eye. cosmetic, pharmaceutical or dermatological.

13. Combination according to any one of claims 1 to 10 for its use to convey active molecules to the deep layers of the epidermis and the upper layers of the dermis.

14. Combination according to claim 13, characterized in that the active molecules have a hydrating power.

15. Combination according to any one of claims 1 to 10, for its use for conveying active molecules to the Langerhans cells in order to initiate, stimulate and / or their action.

16. Combination according to any one of claims 1 to 10, for its use to convey active molecules to dermal fibroblasts to initiate, stimulate and / or their action.

17. Combination according to any one of claims 1 to 10 for its use to convey active molecules to the melanocytes to initiate, stimulate and / or their action on cutaneous pigmentation.

18. Combination according to any one of claims 1 to 10, for its use for conveying anesthetic active molecules to the nerve fibers.

19. Combination according to any one of claims 1 to 10, for its use for conveying active molecules, for the purpose of correcting cutaneous pathologies whose origin lies between the lower layers of the epidermis and the upper layers of the dermis. .