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WO2015082857A1 - Combination of two compounds stemming from fatty acids - Google Patents

Combination of two compounds stemming from fatty acids Download PDF

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Publication number
WO2015082857A1
WO2015082857A1 PCT/FR2014/053174 FR2014053174W WO2015082857A1 WO 2015082857 A1 WO2015082857 A1 WO 2015082857A1 FR 2014053174 W FR2014053174 W FR 2014053174W WO 2015082857 A1 WO2015082857 A1 WO 2015082857A1
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WO
WIPO (PCT)
Prior art keywords
acid
combination
combination according
compound
fatty acids
Prior art date
Application number
PCT/FR2014/053174
Other languages
French (fr)
Inventor
Alexandra Fregonese
Alexandre EVEILLARD
Original Assignee
Innovi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of WO2015082857A1 publication Critical patent/WO2015082857A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to a combination of at least two compounds derived from fatty acids and its use in cosmetology, in pharmaceuticals, 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 intended to promote the bioavailability of molecules, in particular active at the cutaneous level.
  • a combination of the invention allows and / or promotes the penetration and / or action of active molecules, including molecules of high molecular weight and / or not readily available at their target site, such as the middle layers of the skin, in particular in order to reach the basal layers and / or the living cells of the epidermis.
  • active molecules including molecules of high molecular weight and / or not readily available at their target site, such as the middle layers of the skin, in particular in order to reach the basal layers and / or the living cells of the epidermis.
  • it ensures a homogeneous diffusion and also allows to maintain them in the middle 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, digestive tract, 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.
  • the human skin consists of three superimposed layers of tissue, which communicate from the deepest to the most superficial: the hypodermis, the dermis, and the epidermis separated by the dermoepidermal 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 dendritic cells of the 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%) mainly type 1 and 3, responsible for the mechanical strength of the skin, while elastin fibers, they participate in its elasticity.
  • nerve corpuscles 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 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.
  • 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.
  • 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, which converge many bundles of intermediate filaments, ensuring the intercellular mechanical cohesion.
  • 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.
  • 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.
  • 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 mainly 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. Moreover, in these regions, lipid structural changes induced by permeability enhancing 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 to promote the penetration of molecules, especially active, 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.
  • 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 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 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.
  • the compound (s) and the compound (s) are present together in the combination in a proportion of at least 25%, preferably at least 50% by weight relative to to the mass of the suit. This proportion is outside water.
  • a combination consists of one or more compounds (a) and one or more compounds (b).
  • consists it is understood that one or more agents, for example promoting the intimate mixing of the compound (s) and the compound (s) (b) or texture, can be added to said combination.
  • Compound (a) can be obtained from all fatty acids. Saturated fatty acids are however preferred.
  • saturated fatty acids the following acids: formic acid (or methanoic acid) C1: 0
  • tridecyl acid (or tridecanoic acid)
  • C13 0 myristic acid (or tetradecanoic acid)
  • C14 0 pentadecyl acid (or pentadecanoic acid)
  • C15 0
  • laceroic acid or dotriacontanoic acid C32: 0
  • palmitoleic acid or 9Z-hexadecenoic acid
  • linoleic acid 018: 2 ⁇ -6 ⁇ -linolenic acid (or 9Z, 12Z, 15Z-octadecatrienoic acid)
  • C18 3 ⁇ -3 ⁇ -linolenic acid (or acid 6Z, 9Z, 12Z -octadecatrienoic)
  • C18 3 ⁇ -6 dihomo- ⁇ -linolenic acid (or 8Z, 11Z, 14Z-eicosatrienoic acid)
  • C20 3 ⁇ -6 arachidonic acid (or 5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid )
  • docosahexaenoic acid (or 4Z, 7Z, 10Z, 13Z, 16Z, 19Z-docosahexaenoic acid) C22: 6 ⁇ -3.
  • 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.
  • Laurel bay oil including:
  • Monounsaturated AG Oleic acid (40.32%)
  • Polyunsaturated essential fatty acids linoleic acid (23.80%), linolenic acid (0.83%).
  • Palm oil derived from the pulp of the fruit of the palm tree Elaeis guineensis, and comprising:
  • Saturated fatty acids 48.8%
  • palmitic acid 44.0%)
  • stearic acid 4.4%)
  • Palm kernel oil derived from the seed of the fruit of the palm tree Elaeis guineensis, and comprising:
  • Saturated fatty acids (82%) including lauric acid (48.2%), myristic acid (16.2%), palmitic acid (8.4%), capric acid (3.4%), caprylic acid (3.3%), stearic acid (2.5%)
  • Astrocaryum murumuru and comprising:
  • Saturated fatty acids (88.6%) including lauric acid (49.8%), myristic acid
  • Tucuma butter obtained from an Amazonian palm tree, the Astrocaryum tucuma, and comprising:
  • Cocoa butter obtained from the cold pressing of the cocoa bean
  • Saturated fatty acids including stearic acid (33.0%), palmitic acid (26.2%)
  • linoleic acid (omega 6) (3.3%) Cupuaçu butter, derived from the seed of a tree, Theobroma grandifolium, and comprising:
  • Saturated fatty acids (49%) including stearic acid (30.8%), arachidic acid
  • Sal butter or tallow from Borneo obtained from the fruit cores of Shorea robusta, and including:
  • Saturated fatty acids including stearic acid (42.7%), palmitic acid (12.9%)
  • Kokum butter also called Gurgi nut fat, derived from the seed of Garcinia indica, and comprising:
  • Saturated fatty acids including palmitic acid (17.55%), stearic acid
  • Polyunsaturated essential fatty acids linoleic acid (omega-6) (4.08%) Kpangnan butter. also called golden shea butter or Kanya butter, derived from the seed of Pentadesma butyracea, and comprising:
  • Saturated fatty acids 47.7%
  • stearic acid (40.00%)
  • palmitic acid (7.70%)
  • Mango butter obtained by cold pressing of the kernel kernel of the mango, and comprising:
  • Saturated fatty acids including iso-stearic acid (36.66%), palmitic acid (14.96%)
  • the alkanolamine is chosen from mono-, di- and triethanolamine. More preferably, it is monoethanolamine.
  • the compound or compounds (a) are chosen from lauric monoethanolamide, lauric diethanolamide, their mixtures and any mixture of lauric monoethanolamide and / or lauric diethanolamide with another compound (a) resulting from the condensation of a fatty acid or mixture of fatty acids with an alkanolamine.
  • the compound (a) is lauric mono- or di-ethanolamide, resulting from a condensation of lauric acid with mono- or di-ethanolamine, or mono- or di-ethanolamine.
  • the diethanolamide of coconut oil fatty acids resulting from a condensation of a mixture of coconut oil fatty acid, in which lauric acid is predominant, with mono- or di-ethanolamine.
  • Compound (b) is a water-soluble compound of formula RCOR '.
  • 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.
  • 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.
  • R' represents a hydrophilic group, organic or inorganic, ionic or not, capable of conferring on the compound (b) its water solubility.
  • R may represent an amino acid residue or its salt.
  • Amino acid includes standard (or protein) amino acids and non-standard amino acids such as pyroglutamic acid.
  • amino acid residue is meant the remaining residue of the amino acid covalently bound to the carbon atom of the formula RCOR '.
  • compound (b) is different from cocamidopropyl betaine.
  • the compound (b) is chosen from compounds derived from the condensation of a mixture of fatty acids of olive oil or coconut oil and a salt of glutamic acid or pyroglutamic acid.
  • it is preferably chosen from potassium potassium Olivoyl-PCA, resulting from the condensation of a mixture of fatty acids of olive oil with the potassium salt of pyroglutamic acid, cocoyl potassium-PCA from the condensation of a mixture of coconut oil fatty acids with the potassium salt of pyroglutamic acid and Sodium olivoyl glutamate (or olivoyl glutamate sodium).
  • 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.
  • Pyroglutamic acid or pyrrolidonecarboxylic acid, also known by the acronym PCA
  • PCA pyrrolidonecarboxylic acid
  • 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 abundant in collagen: proline and hydroxyproline.
  • proline and hydroxyproline represent approximately 21% of the constituent amino acids of collagen, the remainder consisting mainly of glycine (35%) and alanine (11%).
  • the abundance of the proline / hydroxyproline combination is responsible for the rigidity and stability of collagen.
  • L-PCA is therefore a moisturizing element of choice. Many studies have attributed this action to its hygroscopic power. 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, heating preferably until the fusion of the compounds is necessary to obtain a complete mixture.
  • this heating is performed after mixing the compounds, but alternatively, each compound (a) and (b) can be first melted and then mixed, whether or not the heating continues.
  • 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 combination. .
  • 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 ranging from 15 to 85%. preferably from 40 to 85%, the proportions being expressed by weight relative to the mass of the combination.
  • a cosmetic, pharmaceutical or dermatological composition for topical use comprising a combination of the invention, and excipients acceptable from the 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 molecules with biovector properties for all molecules whose cosmetic, dermatological and / or pharmaceutical interest is located on the middle layers of the skin.
  • the invention relates to all the aforementioned uses of a combination described above in a cosmetic, pharmaceutical or dermatological composition for topical use.
  • the present invention will be able to be associated with all naturally bioavailable substances or not, intended to act on the cells of the epidermis and / or the basal lamina to stimulate, protect, and / or inhibit.
  • 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 cutaneous hydration by promoting penetration and diffusion for example 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) only contains 15% 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. Maintaining a good cutaneous hydration, passes by:
  • 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.
  • 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.
  • the present invention 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 with a view to stimulating them and / or 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.
  • Skin pigmentation is a complex process that begins with the synthesis of melanin by melanocytes.
  • melanocytes In humans, the entire population of melanocytes is localized in the hair follicles and in the basal layer of the epidermis.
  • 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 epidermal and / or basal cell membranes.
  • 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 innerver the epidermis (binding to nervous corpuscles in the dermis acting as 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 effectiveness and / or their speed of action, whether or not this list is limiting, anesthetics and / or cutaneous topicals used in medicine. aesthetic.
  • 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.
  • 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 the 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 coloring agent.
  • Potassium Olivoyl-PCA is a mixture of fatty acids of olive oil condensed with the potassium salt of pyroglutamic acid. PCA is usually obtained from wheat gluten and then partially hydrolysed wheat proteins.
  • 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.
  • This reaction consists of hydrolyzing fatty acids in an alkaline medium with a base of potassium hydroxide (KOH) or sodium hydroxide (NaOH).
  • KOH potassium hydroxide
  • NaOH sodium hydroxide
  • the 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 fat produces glycerol and a mixture of carboxylates (sodium or potassium) which constitutes the soap.
  • 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.
  • Various combinations of the invention are prepared from (a) lauric monoethanolamide and (b) potassium Olivoyl-PCA, the proportions of which, by weight relative to the total weight of the combination, have varied from 0-75% for (a) and 25-100% for (b).
  • compositions were prepared according to the following protocol for a total mass of 100 g:
  • the mixture is homogenized using a mixer (different types of mixers can be used: spatula, vortex, propeller, ⁇ ⁇ )
  • Wipe the skin is wiped without rinsing with the aid of paper towels ( Figures 1 B and 2B).
  • 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
  • Example 3 The test described in Example 3 was carried out for each of the combinations A-Q.
  • the intensity of penetration was evaluated on a scale of 0 to 10. 0 being the total absence penetration and the optimal penetration obtained.
  • 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.
  • the combinations correspond to those for penetrating the molecules between the deep layers of the epidermis and the upper layers of the dermis.
  • coconut oil fatty acid monoethanolamide (Cocamide MEA) and potassium salt of coconut oil pyrrolidone fatty acids (Potassium cocoyl PCA)
  • a skin penetration test was performed with combination I as follows on human 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).
  • rinsing with detergent and water was performed for 10 seconds.
  • the dye was completely leached while with the combination of the invention, the color remains in the middle layers of the skin.

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Abstract

The invention relates to a combination of two compounds stemming from fatty acids and to the cosmetic and dermatological uses of said combination, the latter being a combination of at least one compound (a) stemming from the condensation of at least one fatty acid with an alkanolamine, and at least one hydrosoluble compound (b) of formula RCOR' where R represents a hydrocarbonated chain having between 3 and 35 carbon atoms, and R' represents an amino acid radical or an amino acid salt, each of (a) and (b) being present in a proportion of at least 1 mass % in relation to the mass of the combination.

Description

COMBINAISON DE DEUX COMPOSES ISSUS D'ACIDES GRAS  COMBINATION OF TWO COMPOUNDS FROM FATTY ACIDS
La présente invention concerne une combinaison d'au moins deux composés issus d'acides gras et son utilisation en cosmétologie, en pharmaceutique, notamment en dermatologie, en particulier pour faciliter la pénétration transcutanée de molécules. The present invention relates to a combination of at least two compounds derived from fatty acids and its use in cosmetology, in pharmaceuticals, especially in dermatology, in particular to facilitate the transcutaneous penetration of molecules.
Elle concerne également une composition cosmétique, pharmaceutique, notamment dermatologique comprenant une telle combinaison destinée à favoriser la biodisponibilité de molécules, notamment actives au niveau cutané.  It also relates to a cosmetic, pharmaceutical, especially dermatological composition comprising such a combination intended to promote the bioavailability of molecules, in particular active at the cutaneous level.
Une combinaison de l'invention permet et/ou favorise la pénétration et/ou l'action de molécules actives, y inclus les molécules de haut poids moléculaire et/ou peu disponibles sur leur site cible, comme les couches médianes de la peau, notamment en vue d'atteindre les couches basales et/ou les cellules vivantes de l'épiderme. De manière surprenante, elle en assure une diffusion homogène et permet aussi de les maintenir dans les couches médianes, telles que les couches inférieures de l'épiderme et les couches supérieures du derme des différents épithéliums du corps humain, comme l'épithélium cutané, la cavité buccale, le tractus digestif, la cavité vaginale, ...  A combination of the invention allows and / or promotes the penetration and / or action of active molecules, including molecules of high molecular weight and / or not readily available at their target site, such as the middle layers of the skin, in particular in order to reach the basal layers and / or the living cells of the epidermis. Surprisingly, it ensures a homogeneous diffusion and also allows to maintain them in the middle 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, digestive tract, vaginal cavity, ...
Une combinaison de l'invention permet de réduire la perte de la ou desdites molécules, qu'elles soient contenues dans la combinaison ou appliquées avant ou après la combinaison, au travers des différentes couches cellulaires lors de la pénétration cutanée, notamment mais pas exclusivement, au travers de la couche cornée.  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.
La peau humaine est constituée de trois couches tissulaires principales superposées et qui communiquent, de la plus profonde à la plus superficielle : l'hypoderme, le derme et l'épiderme séparés par la jonction dermo- épidermique.  The human skin consists of three superimposed layers of tissue, which communicate from the deepest to the most superficial: the hypodermis, the dermis, and the epidermis separated by the dermoepidermal junction.
L'hypoderme est la couche la plus profonde et la plus épaisse de la peau. L'hypoderme est un tissu fibro-adipeux essentiellement composé d'adipocytes, cellules spécialisées dans le stockage des lipides, regroupés en lobules et séparés par du tissu conjonctif. Il joue le rôle d'isolant thermique, de réserve énergétique et de protection contre les chocs.  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.
Le derme est un tissu conjonctif innervé et vascularisé d'origine mésenchymateuse constitué principalement d'eau et de fibres protéiques noyées dans un gel réticulaire de mucopolysaccharides et protéoglycanes. Il joue un rôle majeur dans la nutrition, le soutien et la protection de l'épiderme et des annexes cutanées, mais est aussi impliqué dans la thermorégulation, la cicatrisation et la défense contre les pathogènes grâce à la présence de cellules immunitaires, comme les cellules dendritiques du derme, les macrophages et les lymphocytes T. La partie superficielle du derme s'invagine à la jonction avec l'épiderme sous forme de papilles dermiques, augmentant la surface de contact avec l'épiderme et permettant une meilleure adhésion entre ces deux couches. Les papilles dermiques contiennent les fibres nerveuses, qui peuvent pénétrer la lame basale pour aller innerver l'épiderme ou être reliées à de véritables corpuscules nerveux dans le derme jouant le rôle de mécanorécepteurs tactiles. Les papilles dermiques sont également composées de vaisseaux sanguins, qui ne rentrent pas dans l'épiderme. Les cellules principales du derme sont les fibroblastes qui vont synthétiser deux types de fibres protéiques : les fibres de collagène et les fibres d'élastine, constituants de la matrice extracellulaire. La grande majorité des fibres présentes dans le derme sont des fibres de collagène (>90%) essentiellement de type 1 et 3, responsables de la résistance mécanique de la peau, alors que les fibres d'élastine, elles, participent à son élasticité. Au niveau du derme plus profond (derme réticulaire) ces fibres vont s'organiser parallèlement à la surface de la peau. On retrouve également à ce niveau des corpuscules nerveux, récepteurs des variations de pression, mais aussi des vaisseaux sanguins et les annexes cutanées : les follicules pileux, associés étroitement aux glandes sébacées et aux glandes sudoripares. 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 dendritic cells of the 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%) mainly type 1 and 3, responsible for the mechanical strength of the skin, while elastin fibers, they 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 blood vessels and cutaneous appendages are also found at this level: the hair follicles, closely associated with the sebaceous glands and the sweat glands.
L'épiderme est un épithélium pluristratifié constitué de quatre couches superposées formées chacune d'une ou plusieurs assises cellulaires.  The epidermis is a pluristratified epithelium consisting of four superimposed layers each formed of one or more cellular layers.
1 ) La couche basale ou germinative est une monocouche de cellules prolifératives rattachées au derme par la jonction dermo-épidermique. Les kératinocytes basaux sont de forme cubique, avec un noyau volumineux et d'abondants mélanosomes. Les kératinocytes de la couche basale sont les seuls à être mitotiquement actifs et relativement indifférenciés. Ils assurent le renouvellement des cellules épithéliales de l'épiderme.  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) La couche épineuse est composée de 5 à 10 assises cellulaires chez l'Homme. Elle doit son nom à la présence de nombreuses « épines » visibles en microscopie optique qui sont en fait des desmosomes, desquels convergent de nombreux faisceaux de filaments intermédiaires, assurant la cohésion mécanique intercellulaire. 3) La couche granuleuse est la dernière couche de cellules vivantes de l'épiderme. Elle est formée de 2 à 3 assises de cellules chez l'Homme, de forme aplatie avec un noyau perpendiculaire à la jonction dermo-épidermique. Des structures tubulo-vésiculaires appelées corps lamellaires ou kératinosomes sont également présentes dans le cytoplasme des kératinocytes granuleux. Elles jouent un rôle majeur dans l'établissement de la fonction de barrière épidermique en déversant leur contenu protéique et lipidique par exocytose à l'interface couche granuleuse/couche cornée conduisant à la formation d'un ciment intercornéocytaire. 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, which converge many bundles of intermediate filaments, ensuring the intercellular mechanical cohesion. 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) La couche cornée est constituée de 25 à 30 couches de cellules mortes et anucléées : les cornéocytes. Les organelles cellulaires et le noyau sont dégradés durant la transformation des kératinocytes granuleux en cornéocytes, la cornification, le cytoplasme faisant place à une matrice fibreuse de kératines et de filaggrine. La membrane cytoplasmique est remplacée par une coque rigide et insoluble, l'enveloppe cornée. La partie la plus profonde de la couche cornée appelée stratum compactum est constituée de cellules cohésives alors que la partie la plus superficielle, le stratum disjonctum, est composée de cellules discohésives.  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.
La couche cornée est généralement modélisée par le modèle simple du mur de briques proposé par Elias avec des lipides intercornéocytaires comme ciment. Un modèle plus élaboré a été réalisé par Forslind en 1994. Ce modèle de «domaines en mosaïque» (domain mosaic model) considère l'organisation supramoléculaire de la matrice lipidique. La majorité des lipides serait en phase orthorhombique ou hexagonale. Dans cet état cristallin, les chaînes acyle des lipides sont principalement en configuration trans. De plus, une partie des lipides serait dans une conformation plus désordonnée. Ces régions plus fluides pourraient représenter le chemin emprunté par les molécules hydrophobes pour diffuser à travers la couche cornée. De plus, dans ces régions, des transformations structurales des lipides induites par des produits augmentant la perméabilité pourraient se produire sans altérer les structures des phases plus ordonnées. Il s'agit du premier modèle suggérant la présence d'une phase fluide dans la couche cornée.  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 mainly 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. Moreover, in these regions, lipid structural changes induced by permeability enhancing 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.
La présente invention apporte une solution pour favoriser la pénétration de molécules, notamment actives, au travers de l'épiderme pour atteindre les couches inférieures de l'épiderme et les couches supérieures du derme. La présente invention apporte une solution à la toxicité de certaines substances en limitant leur diffusion à une zone précise, la zone cible. The present invention provides a solution to promote the penetration of molecules, especially active, 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.
Ainsi, l'invention concerne 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 chaîne hydrocarbonée ayant de 3 à 35 atomes de carbone, et R' représente un groupement hydrophile, organique ou minéral, ionique ou non, capable de conférer au composé (b) son hydrosolubilité, chacun de (a) et (b) étant présent en une proportion d'au moins 1 % en masse par rapport à la masse de la combinaison.  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 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 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.
Selon l'invention, le ou les composés (a) et le ou les composés (b) sont présents, ensemble, dans la combinaison, en une proportion d'au moins 25%, de préférence au moins 50%, en masse par rapport à la masse de la combinaison. Cette proportion s'entend hors eau. Selon une variante avantageuse de l'invention, une combinaison consiste en un ou des composés (a) et en un ou des composés (b). Par « consiste », on comprend qu'un ou des agents, par exemple favorisant le mélange intime du ou des composés (a) et du ou des composés (b), ou de texture, peuvent être ajoutés à ladite combinaison.  According to the invention, the compound (s) and the compound (s) are present together in the combination in a proportion of at least 25%, preferably at least 50% by weight relative to to the mass of the suit. This proportion is outside water. According to an advantageous variant of the invention, a combination consists of one or more compounds (a) and one or more compounds (b). By "consists" it is understood that one or more agents, for example promoting the intimate mixing of the compound (s) and the compound (s) (b) or texture, can be added to said combination.
Le composé (a) peut être obtenu à partir de tous les acides gras. Les acides gras saturés sont toutefois préférés.  Compound (a) can be obtained from all fatty acids. Saturated fatty acids are however preferred.
A titre d'exemple, on peut citer :  By way of example, mention may be made of:
Parmi les acides gras saturés, les acides suivants : acide formique (ou acide méthanoïque) C1 :0  Of the saturated fatty acids, the following acids: formic acid (or methanoic acid) C1: 0
acide acétique (ou acide éthanoïque) C2:0 acetic acid (or ethanoic acid) C2: 0
acide propionique (ou acide propanoïque) C3:0 propionic acid (or propanoic acid) C3: 0
acide butyrique (ou acide butanoïque) C4:0 butyric acid (or butanoic acid) C4: 0
acide valérique (ou acide pentanoïque) C5:0 valeric acid (or pentanoic acid) C5: 0
acide caproïque (ou acide hexanoïque) C6:0 caproic acid (or hexanoic acid) C6: 0
acide énanthique (ou acide heptanoïque) C7:0 enanthic acid (or heptanoic acid) C7: 0
acide caprylique (ou acide octanoïque) C8:0 caprylic acid (or octanoic acid) C8: 0
acide pélargonique (ou acide nonanoïque) C9:0 pelargonic acid (or nonanoic acid) C9: 0
acide caprique (ou acide décanoïque) C10:0 capric acid (or decanoic acid) C10: 0
acide undécylique (ou acide undécanoïque) C1 1 :0 undecylic acid (or undecanoic acid) C1 1: 0
acide laurique (ou acide dodécanoïque) C12:0 lauric acid (or dodecanoic acid) C12: 0
acide tridécylique (ou acide tridécanoïque) C13:0 acide myristique (ou acide tétradécanoïque) C14:0 acide pentadécylique (ou acide pentadécanoïque) C15:0 tridecyl acid (or tridecanoic acid) C13: 0 myristic acid (or tetradecanoic acid) C14: 0 pentadecyl acid (or pentadecanoic acid) C15: 0
acide palmitique (ou acide hexadécanoïque) C16:0 palmitic acid (or hexadecanoic acid) C16: 0
acide margarique (ou acide heptadécanoïque) C17:0 margaric acid (or heptadecanoic acid) C17: 0
acide stéarique (ou acide octodécanoïque) C18:0 stearic acid (or octodecanoic acid) C18: 0
acide nonadécylique (ou acide nonadécanoïque) C19:0 nonadecyl acid (or nonadecanoic acid) C19: 0
acide arachidique (ou acide eicosanoïque) C20:0 arachidic acid (or eicosanoic acid) C20: 0
acide béhénique (ou acide docosanoïque) C22:0 Behenic acid (or docosanoic acid) C22: 0
acide lignocérique (ou acide tétracosanoïque) C24:0 lignoceric acid (or tetracosanoic acid) C24: 0
acide cérotique (ou acide hexacosanoïque) C26:0 cerotic acid (or hexacosanoic acid) C26: 0
acide montanique (ou acide octacosanoïque) C28:0 montanic acid (or octacosanoic acid) C28: 0
acide mélissique (ou acide triacontanoïque) C30:0 melissic acid (or triacontanoic acid) C30: 0
acide lacéroïque (ou acide dotriacontanoïque C32:0 laceroic acid (or dotriacontanoic acid C32: 0
parmi les acides gras mono-insaturés, les acides suivants :  of the monounsaturated fatty acids, the following acids:
acide palmitoléique (ou acide 9Z-hexadécénoïque) C16:1 ω-7 palmitoleic acid (or 9Z-hexadecenoic acid) C16: 1 ω-7
acide oléique (ou acide 9Z-octadécénoïque) C18:1 ω-9 oleic acid (or 9Z-octadecenoic acid) C18: 1 ω-9
acide érucique (ou acide 13Z-docosaénoïque) C22:1 ω-9 erucic acid (or 13Z-docosaenoic acid) C22: 1 ω-9
acide nervonique (ou acide 15Z-tétracosaénoïque) C24:1 ω-9 Nervonic acid (or 15Z-tetracosaenoic acid) C24: 1 ω-9
parmi les acides gras poly-insaturés, les acides suivants :  among the polyunsaturated fatty acids, the following acids:
acide linoléique (ou acide 9Z,12Z-octadécadiénoïque) 018:2 ω-6 acide a-linolénique(ou acide 9Z,12Z,15Z-octadécatriénoïque) C18:3 ω-3 acide γ-linolénique (ou acide 6Z,9Z,12Z-octadécatriénoïque) C18:3 ω-6 acide dihomo-Y-linolénique (ou acide 8Z,1 1 Z,14Z-eicosatriénoïque) C20:3 ω-6 acide arachidonique (ou acide 5Z,8Z,1 1 Z,14Z-eicosatétraénoïque)C20:4 ω-6 acide eicosapentaénoïque (ou acide 5Z,8Z,1 1Z,14Z,17Z-eicosapentaénoïque), C20:5 ω-3 linoleic acid (or 9Z, 12Z-octadecadienoic acid) 018: 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-γ-linolenic acid (or 8Z, 11Z, 14Z-eicosatrienoic acid) C20: 3 ω-6 arachidonic acid (or 5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid ) C20: 4 ω-6 eicosapentaenoic acid (or 5Z, 8Z, 1 1Z, 14Z, 17Z-eicosapentaenoic acid), C20: 5 ω-3
acide docosahexaénoïque (ou acide 4Z,7Z,10Z,13Z,16Z,19Z- docosahexaénoïque) C22:6 ω-3.  docosahexaenoic acid (or 4Z, 7Z, 10Z, 13Z, 16Z, 19Z-docosahexaenoic acid) C22: 6 ω-3.
Dans une variante de l'invention, le ou les acides gras condensés avec l'alcanolamine peuvent être ceux d'un mélange d'acides gras d'une huile et/ou d'un beurre.  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.
Parmi les huiles préférées, on peut citer les suivantes :  Among the preferred oils, the following can be mentioned:
L'huile de baies de laurier, comprenant :  Laurel bay oil, including:
AG saturés (28,63%) dont acide laurique (1 1 ,61 %), acide palmitique (14,87%), acide stéarique (1 ,55%), acide myristique (0,60%)  Saturated fatty acids (28.63%) of which lauric acid (1 1, 61%), palmitic acid (14.87%), stearic acid (1, 55%), myristic acid (0.60%)
AG mono-insaturés : acide oléique (40,32%) AG essentiels poly-insaturés : acide linoléique (23,80%), acide linolénique (0,83%). Monounsaturated AG: Oleic acid (40.32%) Polyunsaturated essential fatty acids: linoleic acid (23.80%), linolenic acid (0.83%).
L'huile de palme, issue de la pulpe du fruit du palmier Elaeis guineensis, et comprenant :  Palm oil, derived from the pulp of the fruit of the palm tree Elaeis guineensis, and comprising:
AG saturés (48,8%) dont acide palmitique (44,0%), acide stéarique (4,4%)  Saturated fatty acids (48.8%) including palmitic acid (44.0%), stearic acid (4.4%)
AG mono-insaturés : acide oléique (38,4%)  Monounsaturated AG: Oleic acid (38.4%)
AG essentiels poly-insaturés: acide linoléique (oméga 6) (9,4%)  Polyunsaturated essential fatty acids: linoleic acid (omega 6) (9.4%)
L'huile de palmiste, issue de la graine du fruit du palmier Elaeis guineensis, et comprenant :  Palm kernel oil, derived from the seed of the fruit of the palm tree Elaeis guineensis, and comprising:
AG saturés (82%) dont acide laurique (48,2%), acide myristique (16,2%), acide palmitique (8.4%), acide caprique (3,4%), acide caprylique (3,3%), acide stéarique (2,5%)  Saturated fatty acids (82%) including 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 mono-insaturés : acide oléique (15,3%)  Monounsaturated AG: Oleic acid (15.3%)
AG poly-insaturés : acide linoléique (2,3%)  Polyunsaturated AG: linoleic acid (2.3%)
Dans une liste de beurres préférés selon l'invention, en particulier en raison de leur richesse en acides gras saturés, on trouve les beurres suivants :  In a list of preferred butters according to the invention, in particular because of their high content of saturated fatty acids, the following butters are found:
Le beurre de murumuru, issu de la pression de la graine de l'arbre Murumuru butter, stemming from the pressure of the seed of the tree
Astrocaryum murumuru, et comprenant : Astrocaryum murumuru, and comprising:
AG saturés (88,6%) dont acide laurique (49,8%), acide myristique Saturated fatty acids (88.6%) including lauric acid (49.8%), myristic acid
(23,5%), acide palmitique (5,8%), acide stéarique (3,4%), acide caprique(23.5%), palmitic acid (5.8%), stearic acid (3.4%), capric acid
(2,1 %), acide caprylique (4,0%) (2.1%), caprylic acid (4.0%)
AG mono-insaturés : acide oléique (oméga 9) (7,1 %)  Monounsaturated AG: oleic acid (omega 9) (7.1%)
AG essentiels poly-insaturés: acide linoléique (oméga 6) (3,1 %)  Polyunsaturated essential fatty acids: linoleic acid (omega 6) (3.1%)
Le beurre Tucuma. obtenu à partir d'un palmier d'Amazonie, l'Astrocaryum tucuma, et comprenant :  Tucuma butter. obtained from an Amazonian palm tree, the Astrocaryum tucuma, and comprising:
AG saturés : acide laurique (46,28%), acide myristique (23,29%), acide stéarique (5,54%), acide palmitique (5,99%)  Saturated fatty acids: lauric acid (46.28%), myristic acid (23.29%), stearic acid (5.54%), palmitic acid (5.99%)
AG mono-insaturés : acide oléique (oméga-9) (10,60%)  Monounsaturated AG: oleic acid (omega-9) (10.60%)
AG essentiels poly-insaturés : acide linoléique (oméga-6) (3,15%) Polyunsaturated essential fatty acids: linoleic acid (omega-6) (3.15%)
Le beurre de cacao, issu de la pression à froid de la fève du cacaotierCocoa butter, obtained from the cold pressing of the cocoa bean
(Theobroma cacao), et comprenant : (Theobroma cacao), and comprising:
AG saturés (59,2%) dont acide stéarique (33,0%), acide palmitique (26,2%)  Saturated fatty acids (59.2%) including stearic acid (33.0%), palmitic acid (26.2%)
AG mono-insaturés: acide oléique (33,2%)  Monounsaturated AG: Oleic acid (33.2%)
AG essentiels poly-insaturés: acide linoléique (oméga 6) (3,3%) Le beurre de Cupuaçu, issu de la graine d'un arbre, le Theobroma grandifolium, et comprenant : Polyunsaturated essential fatty acids: linoleic acid (omega 6) (3.3%) Cupuaçu butter, derived from the seed of a tree, Theobroma grandifolium, and comprising:
AG saturés (49%) dont acide stéarique (30,8%), acide arachidique Saturated fatty acids (49%) including stearic acid (30.8%), arachidic acid
(10,7%), acide palmitique (7,5%) (10.7%), palmitic acid (7.5%)
AG mono-insaturés : acide oléique (oméga-9) (41 ,7%)  Monounsaturated AG: oleic acid (omega-9) (41, 7%)
AG essentiels poly-insaturés : acide linoléique (oméga-6) (5,0%)  Polyunsaturated essential fatty acids: linoleic acid (omega-6) (5.0%)
Le beurre de Sal ou suif de Bornéo, obtenu à partir des noyaux des fruits de Shorea robusta, et comprenant :  Sal butter or tallow from Borneo, obtained from the fruit cores of Shorea robusta, and including:
AG saturés (55.6%) dont acide stéarique (42,7%), acide palmitique (12,9%)  Saturated fatty acids (55.6%) including stearic acid (42.7%), palmitic acid (12.9%)
AG mono-insaturés : acide oléique (oméga-9) (37,30%)  Monounsaturated AG: oleic acid (omega-9) (37.30%)
AG essentiels poly-insaturés : acide linoléique (oméga-6) (2,1 %)  Polyunsaturated essential fatty acids: linoleic acid (omega-6) (2.1%)
Le beurre de Kokum, aussi appelé graisse de noix de Gurgi, issu de la graine de Garcinia indica, et comprenant :  Kokum butter, also called Gurgi nut fat, derived from the seed of Garcinia indica, and comprising:
AG saturés (51 .83%) dont acide palmitique (17,55%), acide stéarique Saturated fatty acids (51.83%) including palmitic acid (17.55%), stearic acid
(34,28%) (34.28%)
AG mono-insaturés : acide oléique (oméga-9) (34,96%)  Monounsaturated AG: oleic acid (omega-9) (34.96%)
AG essentiels poly-insaturés : acide linoléique (oméga-6) (4,08%) Le beurre de Kpangnan. aussi appelé karité doré ou beurre de Kanya, issu de la graine de Pentadesma butyracea, et comprenant :  Polyunsaturated essential fatty acids: linoleic acid (omega-6) (4.08%) Kpangnan butter. also called golden shea butter or Kanya butter, derived from the seed of Pentadesma butyracea, and comprising:
AG saturés (47,7%) dont acide stéarique (40,00%), acide palmitique (7,70%)  Saturated fatty acids (47.7%) including stearic acid (40.00%), palmitic acid (7.70%)
AG mono-insaturés : acide oléique (42,30%)  Monounsaturated AG: Oleic acid (42.30%)
AG essentiels poly-insaturés : acide linoléique (oméga 6) (4,40%) Le beurre de mangue, obtenu par pression à froid de l'amande du noyau de la mangue, et comprenant :  Polyunsaturated essential fatty acids: linoleic acid (omega 6) (4.40%) Mango butter, obtained by cold pressing of the kernel kernel of the mango, and comprising:
AG saturés (54,56%) dont acide iso-stéarique (36,66%), acide palmitique (14,96%)  Saturated fatty acids (54.56%) including iso-stearic acid (36.66%), palmitic acid (14.96%)
AG mono-insaturés : acide oléique (oméga-9) (39,87%)  Monounsaturated AG: oleic acid (omega-9) (39.87%)
AG essentiels poly-insaturés : acide linoléique (oméga-6) (4,56%) Polyunsaturated essential fatty acids: linoleic acid (omega-6) (4.56%)
Dans cette liste, les proportions d'AG sont exprimées en masse d'AG pour 100 g de beurre. In this list, the proportions of AG are expressed as AG mass per 100 g of butter.
L'alcanolamine conduisant au(x) composé(s) (a) répond à la formule N(H)n[(CH2)mOH]p[(CH2)m'OH]p< où n est égal à 0, 1 ou 2, p et p', identiques ou différents, sont égaux à 1 , 2 ou 3, avec n + p + p' = 3, et m et m', identiques ou différents, varient de 1 à 10, de préférence de 1 à 5. Avantageusement, l'alcanolamine est choisie parmi la mono-, la di- et la tri-éthanolamine. De manière encore préférée, c'est la monoéthanolamine. The alkanolamine leading to the compound (s) (a) has the formula N (H) n [(CH 2) mOH] p [(CH 2 ) nOH] p <where n is 0, 1 or 2, p and p ', which are 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 triethanolamine. More preferably, it is monoethanolamine.
Ainsi, selon une combinaison avantageuse, le ou les composés (a) sont choisis parmi le monoéthanolamide laurique, le diéthanolamide laurique, leurs mélanges et tout mélange du monoéthanolamide laurique et/ou du diéthanolamide laurique avec un autre composé (a) issu de la condensation d'un acide gras ou d'un mélange d'acides gras avec une alcanolamine.  Thus, according to an advantageous combination, the compound or compounds (a) are chosen from lauric monoethanolamide, lauric diethanolamide, their mixtures and any mixture of lauric monoethanolamide and / or lauric diethanolamide with another compound (a) resulting from the condensation of a fatty acid or mixture of fatty acids with an alkanolamine.
Dans une variante avantageuse de l'invention, le composé (a) est le mono- ou le di-éthanolamide laurique, issu d'une condensation de l'acide laurique avec la mono- ou la di-éthanolamine, ou le mono- ou le diéthanolamide d'acides gras d'huile de coco, issu d'une condensation d'un mélange d'acide gras d'huile de coco, dans lequel l'acide laurique est majoritaire, avec la mono- ou la di-éthanolamine.  In an advantageous variant of the invention, the compound (a) is lauric mono- or di-ethanolamide, resulting from a condensation of lauric acid with mono- or di-ethanolamine, or mono- or di-ethanolamine. the diethanolamide of coconut oil fatty acids, resulting from a condensation of a mixture of coconut oil fatty acid, in which lauric acid is predominant, with mono- or di-ethanolamine.
Le composé (b) est un composé hydrosoluble de formule RCOR'.  Compound (b) is a water-soluble compound of formula RCOR '.
Dans cette formule, R représente une chaîne hydrocarbonée d'un acide gras, ledit acide gras pouvant être choisi parmi l'ensemble des acides gras décrits ci-dessus dans le cadre de la définition du composé (a), ledit acide gras pouvant être identique ou différent. Ainsi, R est de préférence une chaîne hydrocarbonée, ayant de 3 à 35 atomes de carbone. Cette chaîne hydrocarbonée peut être saturée ou insaturée, elle est de préférence non cyclique.  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.
Dans la formule RCOR', R' représente un groupement hydrophile, organique ou minéral, ionique ou non, capable de conférer au composé (b) son hydrosolubilité. Dans une variante préférée de l'invention, R peut représenter un reste d'acide aminé ou de son sel. Par acide aminé, on comprend les acides aminés standard (ou protéiques) et les acides aminés non standard comme l'acide pyroglutamique. Par reste d'acide aminé, on entend le résidu restant de l'acide aminé lié par covalence à l'atome de carbone de la formule RCOR'.  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 (or protein) amino acids and non-standard amino acids such as pyroglutamic acid. By amino acid residue is meant the remaining residue of the amino acid covalently bound to the carbon atom of the formula RCOR '.
De préférence, le composé (b) est différent de la bétaïne de cocamidopropyle.  Preferably, compound (b) is different from cocamidopropyl betaine.
Dans une variante avantageuse de l'invention, le composé (b) est choisi parmi les composés issus de la condensation d'un mélange d'acides gras d'huile d'olive ou d'huile de coco et d'un sel de l'acide glutamique ou pyroglutamique. Ainsi, il est de préférence choisi parmi le Potassium Olivoyl- PCA, issu de la condensation d'un mélange d'acides gras d'huile d'olive avec le sel potassique de l'acide pyroglutamique, le Potassium Cocoyl-PCA issu de la condensation d'un mélange d'acides gras d'huile de coco avec le sel potassique de l'acide pyroglutamique et le Sodium olivoyl-glutamate (ou olivoyl glutamate de sodium). In an advantageous variant of the invention, the compound (b) is chosen from compounds derived from the condensation of a mixture of fatty acids of olive oil or coconut oil and a salt of glutamic acid or pyroglutamic acid. Thus, it is preferably chosen from potassium potassium Olivoyl-PCA, resulting from the condensation of a mixture of fatty acids of olive oil with the potassium salt of pyroglutamic acid, cocoyl potassium-PCA from the condensation of a mixture of coconut oil fatty acids with the potassium salt of pyroglutamic acid and Sodium olivoyl glutamate (or olivoyl glutamate sodium).
Un composé (b) préféré de l'invention est le Potassium Olivoyl-PCA. Ce composé est disponible dans le commerce, il peut aussi être obtenu par condensation entre un mélange d'acides gras d'huile d'olive avec le pyroglutamate, de potassium par exemple. L'acide pyroglutamique (ou l'acide pyrrolidone-carboxylique, aussi connu sous l'acronyme PCA), ou son sel, est une molécule physiologique présente dans de nombreux tissus. Même si l'on retrouve 97% du PCA total dans l'épiderme, on observe la présence d'acide L- pyrrolidone carboxylique dans plusieurs organes comme le cerveau, le foie, et dans des fluides biologiques. Le L-PCA est un intermédiaire biochimique de composés présents en abondance dans le collagène : la proline et l'hydroxyproline. Cette information est tout particulièrement intéressante lorsque l'on sait que, ensemble, proline et hydroxyproline représentent environ 21 % des acides aminés constitutifs du collagène, le reste étant principalement constitué de glycine (35%) et d'alanine (1 1 %). L'abondance de l'ensemble proline/hydroxyproline est responsable de la rigidité et de la stabilité du collagène.  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. Pyroglutamic acid (or pyrrolidonecarboxylic acid, also known by the acronym 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 abundant in collagen: proline and hydroxyproline. This information is of particular interest when it is known that, together, proline and hydroxyproline represent approximately 21% of the constituent amino acids of collagen, the remainder consisting mainly of glycine (35%) and alanine (11%). The abundance of the proline / hydroxyproline combination is responsible for the rigidity and stability of collagen.
Dans l'organisme et plus particulièrement au niveau cutané, l'acide pyroglutamique est un excellent agent de différenciation de l'épiderme favorisant la synthèse des lipides épidermique et la maturation de la filaggrine. Présent en quantité importante dans la filaggrine (27%) puis dans le facteur naturel d'hydratation (NMF) (12%), le L-PCA est donc un élément hydratant de choix. De nombreuses études ont attribué cette action à son pouvoir hygroscopique. L'hydratation étant vitale pour maintenir l'élasticité et la flexibilité de la couche cornée, l'action du L-PCA est primordiale.  In the body and more particularly at the cutaneous level, pyroglutamic acid is an excellent differentiating agent of the epidermis favoring the synthesis of epidermal lipids and the ripening of filaggrin. Present in large quantities in filaggrin (27%) and 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 hygroscopic power. Since hydration is vital for maintaining the elasticity and flexibility of the stratum corneum, the action of L-PCA is essential.
Une combinaison de l'invention est préparée par simple mélange des différents composés (a) et (b), selon un ordre indifférent. Compte tenu de leur nature et donc de leur présentation, un chauffage de préférence jusqu'à la fusion des composés est nécessaire pour en obtenir un mélange complet. Avantageusement, ce chauffage est effectué après mélange des composés, mais alternativement, chaque composé (a) et (b) peut être d'abord mis à fondre puis mélangés, en poursuivant ou non le chauffage. Selon l'invention, la proportion du ou des composés (a) varie de 1 à 99% et celle du ou des composés (b) varie de 1 à 99%, ces proportions étant exprimées en masse par rapport à la masse de la combinaison. 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, heating preferably until the fusion of the compounds is necessary to obtain a complete mixture. Advantageously, this heating is performed after mixing the compounds, but alternatively, each compound (a) and (b) can be first melted and then mixed, whether or not the heating continues. 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 combination. .
Avantageusement, le monoéthanolamide d'acides gras d'huile de coco est présent en une proportion variant de 15 à 85%, de préférence de 15 à 60%, et/ou le Potassium Olivoyl-PCA en une proportion variant de 15 à 85%, de préférence de 40 à 85%, les proportions étant exprimées en masse par rapport à la masse de la combinaison.  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 ranging from 15 to 85%. preferably from 40 to 85%, the proportions being expressed by weight relative to the mass of the combination.
Elle concerne aussi une composition cosmétique, pharmaceutique, ou dermatologique à usage topique, comprenant une combinaison de l'invention, et des excipients acceptables du point de vue cosmétique, pharmaceutique ou dermatologique, et éventuellement un ou des ingrédients actifs cosmétiques, pharmaceutiques ou dermatologiques. La présente invention concerne un mélange de molécules, aux propriétés de biovecteur pour toutes les molécules dont l'intérêt cosmétique, dermatologique et/ou pharmaceutique se situe sur les couches médianes de la peau. L'invention concerne toutes les utilisations précitées d'une combinaison décrite précédemment dans une composition cosmétique, pharmaceutique, ou dermatologique à usage topique.  It also relates to a cosmetic, pharmaceutical or dermatological composition for topical use, comprising a combination of the invention, and excipients acceptable from the 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 molecules with biovector properties for all molecules whose cosmetic, dermatological and / or pharmaceutical interest is located on the middle layers of the skin. The invention relates to all the aforementioned uses of a combination described above in a cosmetic, pharmaceutical or dermatological composition for topical use.
La présente invention va pouvoir être associée à toutes les substances naturellement biodisponibles ou non, destinées à agir sur les cellules de l'épiderme et/ou de la lame basale en vue de les stimuler, de les protéger, et/ou de les inhiber. Sont notamment concernés et non exclusivement les cellules de Langerhans, les fibroblastes, les mélanocytes, les kératinocytes et la matrice extracellulaire.  The present invention will be able to be associated with all naturally bioavailable substances or not, intended to act on the cells of the epidermis and / or the basal lamina to stimulate, protect, and / or inhibit. Particularly concerned and not exclusively Langerhans cells, fibroblasts, melanocytes, keratinocytes and extracellular matrix.
La présente invention concerne une combinaison de deux composés définis précédemment, qui permet et/ou favorise la pénétration percutanée de molécules actives. La pénétration cutanée de molécules actives dépend notamment du poids moléculaire de la molécule, de son hydrophilie ou lipophilie, de son point de fusion, de son pH et de son ionisation, de sa concentration. Des molécules de haut poids moléculaire possèdent une pénétration cutanée faible ou inexistante (acide hyaluronique, collagène, vitamine D, ...). La présente invention permet de s'affranchir en partie des contraintes liées aux caractéristiques physico-chimiques de la molécule en la véhiculant sur son site d'action.  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.
Une combinaison de l'invention, grâce à ses capacités de biovecteur peut agir sur l'hydratation cutanée en favorisant la pénétration et la diffusion par exemple de molécules hygroscopiques souvent difficiles à faire pénétrer en raison notamment du haut poids moléculaire desdites substances. A combination of the invention, thanks to its biovector capabilities can act on cutaneous hydration by promoting penetration and diffusion for example hygroscopic molecules often difficult to penetrate due in particular to the high molecular weight of said substances.
Une bonne hydratation cutanée est indispensable pour conférer à la peau souplesse, élasticité et une certaine imperméabilité. Le derme est le principal réservoir d'eau de la peau, grâce à des protéoglycanes tel que l'acide hyaluronique, molécules ayant des propriétés hygroscopiques exceptionnelles. Sa teneur en eau est de 80%. De la couche basale à la couche granuleuse, l'épiderme humain contient de 65 à 70% d'eau mais ce taux diminue au niveau du stratum compactum où il n'est plus que de 40%. La couche superficielle de la couche cornée (stratum disjunctum) ne contient plus quant à elle que 15% d'eau. Ce gradient est dû à la disparition de constituants ayant la capacité de retenir l'eau : acides nucléiques, protéines et phospholipides. Ce gradient d'hydratation décroissant permet à l'eau libre du derme de diffuser des couches les plus profondes jusqu'aux plus superficielles. Le maintien d'une bonne hydratation cutanée, passe par :  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) only contains 15% 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. Maintaining a good cutaneous hydration, passes by:
- la diminution de l'évaporation, et  - the decrease of evaporation, and
- l'augmentation de la fixation de l'eau lors de son passage à travers le stratum corneum.  - the increase in the fixation of the water during its passage through the stratum corneum.
L'adjonction de l'invention à une formulation cosmétique, dermatologique et/ou pharmaceutique facilite la pénétration et la fixation de molécules hygroscopiques qui fixent l'eau et participe à la diminution de l'évaporation.  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.
La présente invention, grâce à ses capacités de biovecteur peut agir sur les défenses cutanées en favorisant la diffusion par exemple de molécules activant les cellules de Langerhans.  The present invention, thanks to its biovector capabilities can act on the skin defenses by promoting the diffusion of eg Langerhans cells activating molecules.
Les cellules de Langerhans, situées au niveau du derme constituent le système immunitaire de la peau. La peau représentant la surface de contact la plus importante avec les éléments potentiellement pathogènes de l'environnement extérieur (virus, bactéries, toxiques, ...), il est indispensable d'avoir un système de défense performant. Toutefois, ces cellules étant enchâssées dans l'épiderme, il sera avantageux d'associer à tous types d'agents actifs, la présente invention afin de pouvoir traverser la couche cornée et atteindre les cellules de Langerhans en vue de les stimuler et/ou d'initier leur action. La présente invention, grâce à ses capacités de biovecteur peut agir sur la matrice extracellulaire du derme en agissant par exemple sur les fibroblastes. 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 with a view to stimulating them and / or 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.
Les fibroblastes sont les principales cellules du derme. Ils sont spécialisés dans la synthèse de deux types de fibres protéiques : les fibres de collagène et les fibres d'élastines constituantes de la matrice extracellulaire. Ces fibres confèrent à la peau sa résistance aux tensions et aux tractions ainsi que ses propriétés élastiques. Leur stimulation nécessite de s'affranchir à l'aide de la présente invention de l'imperméabilité relative de la couche cornée ou stratum corneum.  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.
La présente invention, grâce à ses capacités de biovecteur peut agir sur la pigmentation cutanée en agissant par exemple sur les mélanocytes.  The present invention, thanks to its biovector capabilities can act on cutaneous pigmentation by acting for example on melanocytes.
La pigmentation de la peau est un processus complexe qui débute avec la synthèse de la mélanine par les mélanocytes. Chez l'homme, l'ensemble de la population des mélanocytes se localise dans les follicules pileux et dans l'assise basale de l'épiderme. Outre le côté esthétique le rôle majeur des mélanines est de protéger la peau contre les effets néfastes des rayons UV. L'association de molécules stimulant ou inhibant la production de mélanine avec l'invention augmentera la biodisponibilité des substances associées et limitera la déperdition de matières actives au travers des différentes couches cellulaire. La présente invention pourra avantageusement être associée à tous types de molécules antioxydantes en vue de protéger la matrice extracellulaire et/ou les membranes des cellules épidermiques et/ou basales.  Skin pigmentation is a complex process that begins 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 epidermal and / or basal cell membranes.
La présente invention, grâce à ses capacités de biovecteur peut également agir sur un effet anesthésiant. La capacité de l'invention à atteindre les papilles dermiques qui contiennent les fibres nerveuses et qui pénètrent la lame basale pour aller innerver l'épiderme (liaison à des corpuscules nerveux dans le derme jouant le rôle de mécanorécepteurs tactiles) présente un intérêt en cosmétique, notamment, mais non exclusivement, dans le cadre de l'épilation ou des tatouages et/ou de la médecine esthétique. L'invention présente également un intérêt pour les formes médicamenteuses comme les patchs en améliorant leur efficacité et/ou leur rapidité d'action, que ce soit, sans que cette liste ne soit limitative, des anesthésiants et/ou des topiques cutanés utilisés en médecine esthétique.  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 innerver the epidermis (binding to nervous corpuscles in the dermis acting as 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 effectiveness and / or their speed of action, whether or not this list is limiting, anesthetics and / or cutaneous topicals used in medicine. aesthetic.
Une combinaison de l'invention est aussi destinée à véhiculer des molécules actives, en vue de corriger des pathologies cutanées dont l'origine se situe entre les couches inférieures de l'épiderme et les couches supérieures du derme. 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.
De nombreuses pathologies épidermiques sont liées à des défauts dans la composition de l'enveloppe lipidique. Des défauts de l'expression de céramides ainsi qu'une perturbation de l'organisation lamellaire ont été observés dans le psoriasis et la dermatite atopique (Di Nardo, 1998; Ghadially et al., 1995; Madison, 2003). La présente invention, grâce à ses capacités de biovecteur permet de restructurer des défauts dans la composition de l'enveloppe lipidique.  Many epidermal pathologies are related to defects in the composition of the lipid envelope. 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.
La présente invention est maintenant illustrée, de manière non limitative, par les exemples suivants à l'appui des figures 1 -5, selon lesquelles :  The present invention is now illustrated, without limitation, by the following examples in support of FIGS. 1-5, in which:
Les figures 1 et 2 correspondent à des photographies illustrant l'efficacité ex vivo d'une combinaison de l'invention sur la diffusion d'une molécule active, un agent colorant.  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.
La figure 3 est un diagramme représentant le taux de pénétration cutanée (en gain en unité arbitraire, ua) d'une combinaison de l'invention, en fonction des proportions des ingrédients (a) et (b).  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 the ingredients (a) and (b).
Les figures 4 et 5 correspondent à des photographies illustrant l'efficacité in vivo d'une combinaison de l'invention sur la diffusion d'une molécule active, un agent colorant.  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 coloring agent.
Exemple 1 : Préparation d'un composé (b) Example 1 Preparation of a compound (b)
Le Potassium Olivoyl-PCA est un mélange d'acides gras d'huile d'olive condensé avec le sel de potassium de l'acide pyroglutamique. Le PCA est généralement obtenu à partir de gluten de blé puis de protéines de blé partiellement hydrolysées.  Potassium Olivoyl-PCA is a mixture of fatty acids of olive oil condensed with the potassium salt of pyroglutamic acid. PCA is usually obtained from wheat gluten and then partially hydrolysed wheat proteins.
Il est ainsi obtenu des acides gras d'huile d'olive qui sont associés à une partie hydrophile. Selon l'invention, le Potassium Olivoyl-PCA est un composé (b) préféré, mais bien entendu, elle n'y est pas restreinte, et tout dérivé hydrosoluble d'acides gras, est adapté.  It is thus obtained fatty acids of olive oil 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.
Ainsi toutes les méthodes permettant de rendre hydrosoluble un acide gras, un mélange d'acides gras, une huile, un beurre, sont concernées par l'invention. Sans que cela soit exhaustif, on peut citer les réactions suivantes :  Thus, all the methods making it possible to render a fatty acid, a mixture of fatty acids, an oil and a butter water soluble are concerned by the invention. Without being exhaustive, we can cite the following reactions:
- La saponification :  - The saponification:
Cette réaction consiste à l'hydrolyser des acides gras en milieu alcalin par une base: potasse (KOH) ou soude (NaOH). La saponification est une réaction lente mais totale. Pour accélérer la réaction elle peut se réaliser à des températures entre 80 et 100°C et sous agitation constante. La saponification de corps gras produit du glycérol et un mélange de carboxylates (de sodium ou de potassium) qui constitue le savon. This reaction consists of hydrolyzing fatty acids in an alkaline medium with a base of potassium hydroxide (KOH) or sodium hydroxide (NaOH). The 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 fat produces glycerol and a mixture of carboxylates (sodium or potassium) which constitutes the soap.
La sulfatation :  Sulfation:
La sulfatation est le fait d'attacher un ou plusieurs groupement(s) sulfate sur une molécule. Le sulfate est un groupement anionique (chargé négativement) hydrophile (qui a une bonne affinité pour l'eau) ; la sulfatation de l'huile va donc lui donner une partie hydrophile, ce qui la rend soluble dans l'eau.  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.
Exemple 2 : Préparation de combinaisons de l'invention Example 2 Preparation of Combinations of the Invention
Différentes combinaisons de l'invention sont préparées à partir (a) de monoéthanolamide laurique et (b) de Potassium Olivoyl-PCA, dont les proportions, en masse par rapport à la masse totale de la combinaison, ont varié de 0-75% pour (a) et de 25-100% pour (b). Various combinations of the invention are prepared from (a) lauric monoethanolamide and (b) potassium Olivoyl-PCA, the proportions of which, by weight relative to the total weight of the combination, have varied from 0-75% for (a) and 25-100% for (b).
La constitution des combinaisons préparées est précisée dans le tableau 1 suivant : The constitution of the prepared combinations is specified in the following Table 1:
Tableau 1  Table 1
Figure imgf000016_0001
Figure imgf000016_0001
Chacune de ces compositions a été préparée selon le protocole suivant pour une masse totale de 100g : Each of these compositions was prepared according to the following protocol for a total mass of 100 g:
- on pèse dans un bêcher de 250 mL, les différents composés (a) et (b) comme indiqué dans le tableau ci-dessus ;  the different compounds (a) and (b) are weighed into a 250 ml beaker as indicated in the table above;
- on chauffe le mélange jusqu'à obtenir la dissolution complète des composés ;  the mixture is heated until the complete dissolution of the compounds is achieved;
- on homogénéise le mélange à l'aide d'un mélangeur (différents types de mélangeurs peuvent être utilisés : spatule, vortex, hélice, ■■■) - The mixture is homogenized using a mixer (different types of mixers can be used: spatula, vortex, propeller, ■ ■■ )
- et on laisser refroidir le mélange. Une efficacité sur les tests réalisés (décrits dans les exemples suivants) a été observée sur toutes les combinaisons associant les 2 composés, dès que le composé (a) et le composé (b) sont présents à raison d'une proportion d'au moins 1 % et au moins 25%, cette proportion étant exprimée en masse par rapport à la masse de la combinaison, c'est-à-dire pour les échantillons B, C, D, E, F, G, H, I, J, K, L, M, N, O, P et Q. - and allow the mixture to 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.
L'efficacité optimale a été observée avec l'échantillon I (35% de monoéthanolamide laurique et 65% de Potassium Olivoyl-PCA).  The optimal efficiency was observed with the sample I (35% of lauric monoethanolamide and 65% of Potassium Olivoyl-PCA).
Exemple 3 : Efficacité ex vivo d'une combinaison de l'invention sur la diffusion de molécules Example 3 Ex Vivo Efficacy of a Combination of the Invention on the Diffusion of Molecules
Un test de pénétration cutanée a été réalisé avec la combinaison I du tableau 1 ci-dessus, comme suit :  A skin penetration test was performed with combination I of Table 1 above, as follows:
Application de la combinaison I (Figure 2) ou non, à titre de contrôle Application of combination I (Figure 2) or not, as a control
(Figure 1 ) à la surface de la peau d'une oreille de porc. (Figure 1) on the surface of the skin of a pig's ear.
Dépôt d'une goutte de colorant rouge (éosine) sur la zone de la peau traitée (Figure 2) ou non (Figure 1 ) et maintien en contact pendant une minute (Figures 1A et 2A).  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).
Essuyage de la peau est essuyée sans rinçage à l'aide d'un papier absorbant (Figures 1 B et 2B).  Wipe the skin is wiped without rinsing with the aid of paper towels (Figures 1 B and 2B).
Réalisation d'une coupe histologique de 50 μιτι à l'aide d'un vibratome sur la partie centrale de la zone de dépôt de la goutte de colorant. La coupe est ensuite observée au microscope (grossissement x100) pour visualiser le niveau de pénétration et/ou la biodisponibilité du produit au niveau tissulaire (Figures 1 C et 2C).  Achievement of a histological section of 50 μιτι using a vibratome on the central part of the droplet dye drop zone. 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).
On observe que sur la zone de peau non traitée par la combinaison I, le colorant a pénétré superficiellement dans la peau (Figure 1 C) alors que sur la zone de peau traitée, l'application a favorisé la diffusion homogène de l'actif sur les couches médianes de la peau (Figure 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 ingredient over the skin. the middle layers of the skin (Figure 2C).
Exemple 4 : Influence des proportions des composés (a) et (b) dans une combinaison de l'invention sur la diffusion de molécules, ex vivo 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
4.1 ) Monoéthanolamide laurique et Potassium olivoyl PCA (sel de potassium des pyrrolidone-acides gras d'huile d'olive) Le test réalisé précédemment sur oreille de porc a été conduit avec les différentes combinaisons A à Q de l'invention décrites dans le tableau 1 ci- dessus. 4.1) lauric monoethanolamide and Potassium olivoyl PCA (potassium salt of pyrrolidone-fatty acids of olive oil) 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.
Le test décrit à l'exemple 3 a été réalisé pour chacune des combinaisons A-Q.  The test described in Example 3 was carried out for each of the combinations A-Q.
L'intensité de pénétration a été évaluée sur une échelle de 0 à 10. 0 étant l'absence totale pénétration et 10 la pénétration optimale obtenue.  The intensity of penetration was evaluated on a scale of 0 to 10. 0 being the total absence penetration and the optimal penetration obtained.
Les résultats de ces tests sont présentés sur la Figure 3.  The results of these tests are shown in Figure 3.
Le niveau de pénétration 10 correspond à une pénétration profonde au niveau des couches du derme. Les niveaux de pénétration 9 à 5 correspondent à une pénétration se situant respectivement des couches supérieures du derme au couches profondes de l'épiderme. Etant entendu que le niveau de pénétration 8 est le seul qui permet de couvrir totalement l'ensemble de cette zone (couche profonde de l'épiderme et couche supérieure du derme). Le niveau 4 correspond uniquement à une pénétration sur les couches médianes de l'épiderme. Au sens de l'invention, les combinaisons correspondent à celles permettant de faire pénétrer les molécules entre les couches profondes de l'épiderme et les couches supérieures du derme.  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.
Une efficacité a été observée pour les combinaisons D, E, F, G, H, I, J, K, L, M, N O et P. L'efficacité optimale a été observée avec l'échantillon I.  Efficiency was observed for D, E, F, G, H, I, J, K, L, M, N, O and P. Optimal efficacy was observed with Sample I.
4.2) Monoéthanolamide d'acides gras d'huile de coco (Cocamide MEA) et sel de potassium des pyrrolidone-acides gras d'huile de coco (Potassium cocoyl PCA)  4.2) coconut oil fatty acid monoethanolamide (Cocamide MEA) and potassium salt of coconut oil pyrrolidone fatty acids (Potassium cocoyl PCA)
Le test de pénétration décrit à l'exemple 3 a été conduit avec la combinaison Cocamide MEA et Potassium cocoyl PCA avec les mêmes concentrations que celles des combinaisons A à Q du tableau 1 ci-dessus.  The penetration test described in Example 3 was conducted with the combination Cocamide MEA and Potassium cocoyl PCA with the same concentrations as those of combinations A to Q of Table 1 above.
Les niveaux de pénétration observés sont identiques à ceux observés avec les combinaisons monoéthanolamide laurique et Potassium olivoyl PCA, (4.1 )  The penetration levels observed are identical to those observed with lauric monoethanolamide and Potassium olivoyl PCA combinations, (4.1)
4.3) Diéthanolamide d'acides gras d'huile de coco (Cocamide DEA) et cocoyl glutamate de sodium (Sodium cocoyl glutamate)  4.3) Coconut oil fatty acid diethanolamide (Cocamide DEA) and sodium cocoyl glutamate (Sodium cocoyl glutamate)
Le test de pénétration décrit à l'exemple 3 a été conduit avec la combinaison Cocamide DEA et Sodium cocoyl glutamate avec les mêmes concentrations que celles des combinaisons A à Q du tableau 1 ci-dessus. Les niveaux de pénétration observés sont identiques à ceux observés avec les combinaisons monoéthanolamide laurique et Potassium olivoyl PCA, (4.1 ) Exemple 5 : Efficacité in vivo de l'invention sur la diffusion de molécules The penetration test described in Example 3 was conducted with the combination Cocamide DEA and Sodium cocoyl glutamate with the same concentrations as those of combinations A to Q of Table 1 above. The penetration levels observed are identical to those observed with the lauric monoethanolamide and potassium olivoyl PCA combinations, (4.1). EXAMPLE 5 In Vivo Effectiveness of the Invention on the Diffusion of Molecules
Un test de pénétration cutanée a été réalisée avec la combinaison I, comme suit sur de la peau humaine.  A skin penetration test was performed with combination I as follows on human skin.
Afin de démontrer l'efficacité de l'invention sur la diffusion de principes actifs au travers des différentes couches de la peau, la combinaison I a été colorée avec un colorant bleu. La combinaison I colorée (figure 5A) ou le colorant seul (figure 5A) ont été appliqués sur la peau. Une minute après l'application les produits ont été essuyés sans rinçage. Le colorant a pénétré légèrement dans la peau dans le cas contrôle (figure 4B) alors qu'il a non seulement diffusé à la surface de la peau avec la combinaison de l'invention mais également pénétré de manière plus importante (intensité de la couleur) (figure 5B). Dans les deux cas, un rinçage avec un détergent et de l'eau a été réalisé pendant 10 secondes. Dans le cas contrôle, le colorant a totalement été lessivé alors qu'avec la combinaison de l'invention, la coloration reste présente dans les couches médianes de la peau.  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

REVENDICATIONS
1 . 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 chaîne hydrocarbonée ayant de 3 à 35 atomes de carbone, et R' représente un groupement hydrophile, organique ou minéral, ionique ou non, capable de conférer au composé (b) son hydrosolubilité, chacun de (a) et (b) étant présent en une proportion d'au moins 1 % en masse par rapport à la masse de la combinaison. 1. 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 3 at 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 minus 1% by mass relative to the mass of the combination.
2. Combinaison selon la revendication 1 consistant en un ou plusieurs composés (a) et un ou plusieurs composés (b).  2. Combination according to claim 1 consisting of one or more compounds (a) and one or more compounds (b).
3. Combinaison selon la revendication 1 ou 2, caractérisée en ce que le ou les composés (a) sont issus de la condensation d'au moins un acide gras choisi parmi les acides gras saturés, les acides gras mono- et poly-insaturés et leurs mélanges avec une alcanolamine.  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 chosen from saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. their mixtures with an alkanolamine.
4. Combinaison selon l'une quelconque des revendications 1 à 3, caractérisée en ce que le ou les composés (a) sont issus de la condensation d'au moins un acide gras avec la monoéthanolamine.  4. Combination according to any one of claims 1 to 3, characterized in that the compound or compounds (a) are derived from the condensation of at least one fatty acid with monoethanolamine.
5. Combinaison selon l'une quelconque des revendications 1 à 4, caractérisée en ce que R représente la chaîne hydrocarbonée d'un acide gras choisi parmi les acides gras saturés, les acides gras mono- et poly-insaturés et leurs mélanges.  5. Combination according to any one of claims 1 to 4, 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.
6. Combinaison selon l'une quelconque des revendications 1 à 5, caractérisée en ce que le composé (a) est choisi parmi le monoéthanolamide d'acides gras d'huile de coco et le diéthanolamide d'acides gras d'huile de coco.  6. Combination according to any one of claims 1 to 5, characterized in that the compound (a) is selected from coconut oil fatty acid monoethanolamide and coconut oil fatty acid diethanolamide.
7. Combinaison selon l'une quelconque des revendications 1 à 6, caractérisée en ce que R' représente un reste d'acide aminé ou d'un sel d'acide aminé.  7. Combination according to any one of claims 1 to 6, characterized in that R 'represents an amino acid residue or an amino acid salt.
8. Combinaison selon l'une quelconque des revendications 1 à 7, caractérisée en ce que le composé (b) est choisi parmi les composés issus de la condensation d'un mélange d'acides gras d'huile d'olive ou d'huile de coco et d'un sel de l'acide glutamique ou pyroglutamique.  8. Combination according to any one of claims 1 to 7, characterized in that the compound (b) is selected from compounds derived from the condensation of a mixture of fatty acids of olive oil or oil coconut and a salt of glutamic acid or pyroglutamic acid.
9. Combinaison selon l'une quelconque des revendications 1 à 8, caractérisée en ce que la proportion du composé (a) et/ou celle du composé (b) varient de 1 à 99% en masse par rapport à la masse de la combinaison. 9. Combination according to any one of claims 1 to 8, characterized in that the proportion of the compound (a) and / or that of the compound (b) ranges from 1 to 99% by weight relative to the mass of the combination .
10. Combinaison selon l'une quelconque des revendications 1 à 9, caractérisée en ce que la proportion du composé (a) et/ou celle du composé (b) varient de 15 à 85% par rapport à la masse de la combinaison. 10. Combination according to any one of claims 1 to 9, characterized in that the proportion of the compound (a) and / or that of the compound (b) vary from 15 to 85% relative to the weight of the combination.
1 1 . Combinaison selon l'une quelconque des revendications 5 et 6 à 10, caractérisée en ce que l'éthanolamide d'acides gras de coco est présent en une proportion variant de 15 à 60% en masse par rapport à la masse de la combinaison.  1 1. Combination according to any one of claims 5 and 6 to 10, 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 combination.
12. Combinaison selon l'une quelconque des revendications 6 et 7 à 10, caractérisée en ce que le composé (b) est issu de la condensation d'un mélange d'acides gras d'huile d'olive et d'un sel de l'acide pyroglutamique est présent en une proportion variant de 40 à 85% en masse par rapport à la masse de la combinaison.  12. Combination according to any one of claims 6 and 7 to 10, characterized in that the compound (b) is derived from the condensation of a mixture of fatty acids of olive oil and a salt of pyroglutamic acid is present in a proportion ranging from 40 to 85% by weight relative to the mass of the combination.
13. Composition comprenant une combinaison selon l'une quelconque des revendications 1 à 12 et au moins une molécule active.  13. A composition comprising a combination according to any one of claims 1 to 12 and at least one active molecule.
14. Composition cosmétique, pharmaceutique, ou dermatologique à usage topique, une combinaison selon l'une quelconque des revendications 1 à 12, et des excipients acceptables du point de vue cosmétique, pharmaceutique ou dermatologique, et au moins une molécule active du point de vue cosmétique, pharmaceutique ou dermatologique.  Cosmetic, pharmaceutical, or dermatological composition for topical use, a combination according to any one of claims 1 to 12, and excipients acceptable from the cosmetic, pharmaceutical or dermatological point of view, and at least one molecule that is active from the point of view cosmetic, pharmaceutical or dermatological.
15. Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives vers les couches profondes de l'épiderme et les couches supérieures du derme.  15. Use of a combination according to any one of claims 1 to 12, in a composition according to claim 14 for conveying active molecules to the deep layers of the epidermis and the upper layers of the dermis.
16. Utilisation d'une combinaison selon la revendication 15, caractérisée en ce que les molécules actives ont un pouvoir hydratant.  16. Use of a combination according to claim 15, characterized in that the active molecules have a hydrating power.
17. Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives vers les cellules de Langerhans en vue d'initier, stimuler et/ou leur action.  17. Use of a combination according to any one of claims 1 to 12, in a composition according to claim 14 for conveying active molecules to the Langerhans cells in order to initiate, stimulate and / or their action.
18. Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives vers les fibroblastes du derme en vue d'initier, stimuler et/ou leur action.  18. Use of a combination according to any one of claims 1 to 12, in a composition according to claim 14 for conveying active molecules to the fibroblasts of the dermis to initiate, stimulate and / or their action.
19. Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives vers les mélanocytes en vue d'initier, stimuler et/ou leur action sur la pigmentation cutanée. 19. Use of a combination according to any one of claims 1 to 12, in a composition according to claim 14 for to convey active molecules towards the melanocytes in order to initiate, stimulate and / or their action on the cutaneous pigmentation.
20. Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives anesthésiantes vers les fibres nerveuses.  20. Use of a combination according to any one of claims 1 to 12, in a composition according to claim 14 for conveying active anesthetic molecules to the nerve fibers.
21 . Utilisation d'une combinaison selon l'une quelconque des revendications 1 à 12, dans une composition selon la revendication 14 pour véhiculer des molécules actives destinées à corriger des pathologies cutanées dont l'origine se situe entre les couches inférieures de l'épiderme et les couches supérieures du derme.  21. Use of a combination according to any one of Claims 1 to 12, in a composition according to Claim 14 for conveying active molecules intended to correct cutaneous pathologies whose origin lies between the lower layers of the epidermis and the upper layers of the dermis.
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