WO2004093832A2

WO2004093832A2 - Cosmetic or pharmaceutical composition comprising a combination of at least one diacylglycerol and at least one fatty alcohol

Info

Publication number: WO2004093832A2
Application number: PCT/FR2004/000944
Authority: WO
Inventors: Claude Dal Farra; Nouha Domloge; Dominique Peyronel
Original assignee: Societe D'extraction Des Principes Actifs (Vincience Sa)
Priority date: 2003-04-17
Filing date: 2004-04-16
Publication date: 2004-11-04
Also published as: FR2853834A1; FR2853834B1; WO2004093832A3

Abstract

The invention relates to a cosmetic and/or dermatological and/or pharmaceutical composition comprising, by way of active principle, at least a combination of diacylglycerol and at least one fatty alcohol. The invention also relates to the use thereof, for example, to care for the skin and/or skin appendages, as well as to the use thereof in order to treat signs of cutaneous ageing. The invention further relates to a cosmetic treatment method for the skin and/or skin appendages.

Description

Cosmetic or pharmaceutical composition comprising the combination of at least one diacylglycerol and at least one fatty alcohol.

The present invention relates to the pharmaceutical field, in particular the field of dermatology as well as the field of cosmetics.

The subject of the present invention is a cosmetic and / or dermatological and / or pharmaceutical composition comprising, as active principle, at least the combination of diacylglycerol and at least one fatty alcohol.

The invention also includes its use for treating, among other things, the manifestations of skin aging and for protecting the skin against external aggressions.

The skin is a covering organ covering the entire surface of the body. It is a vital organ ensuring multiple functions such as sensitive, protective functions against multiple external aggressions, immune, metabolic or even thermoregulatory. These roles are made possible thanks to a complex structure which combines various tissue structures.

The skin consists of three separate superimposed compartments: the epidermis, the dermis and the hypodermis. The epidermis is a coating epithelium which constitutes the external structure of the skin and ensures its protective function. This function is ensured by the cohesion of the epithelial cells and by the production of a filamentous and resistant protein, keratin. The dermis is a connective tissue made up of a fundamental substance in which fibroblasts, collagen fibers and elastin fibers, protein fibers synthesized by fibroblasts, bathe. Collagen fibers provide a large part of the solidity of the dermis, they participate in the elasticity and especially in the tone of the skin and / or mucous membranes. Below the dermis is a layer of fatty tissue: the hypodermis.

The skin, like all other organs, is subject to aging. The first general manifestation of skin aging is the appearance of fine lines. The skin becomes less supple, thinner, often dry and it loses its elasticity. The loss of suppleness, firmness and hydration of the skin, as well as the appearance of wrinkles and fine lines are probably due to the uneven loss of different types of macromolecules in the skin matrix.

The factors involved in the skin aging process are varied and numerous. The phenomenon of skin aging is accompanied, among other things, by loss of skin functions and a decrease in the response to stimuli to which it may be subjected. All these modifications reside in modifications at the cellular level (Dalziel et al, Clin Exp Dermatol 1991, 16 (5): 315-23). In the epidermis, the slowing down of the proliferation and differentiation of keratinocytes with age is a factor which explains the thinning of the skin during aging. The epidermis atrophies, the skin loses its protective capacity.

The decline in the ability of cells to divide and, in particular, fibroblasts, is characteristic of aged tissue. The fibroblasts, which ensure a balance between synthesis and degradation of the collagen and elastin fibers, will shift this balance towards a degradation of the fibers. This results in a loss of elasticity and tone of the dermis which results in the appearance of wrinkles.

Keratinocytes as well as fibroblasts experience a decrease in their proliferation associated with age which may be due to a loss of response to mitogenesis. Thus, in aged skin, the cells lose their proliferation and repair potential, they decrease the production of "key" proteins such as collagen or elastin.

Chronic exposure to ultraviolet light, in particular to UVA rays and other aggressive environmental factors, accelerates and worsens the aging phenomenon of the skin (called chrono-aging) and leads to a disruption of the expression of genes in the skin. cell proliferation and differentiation.

One of the mechanisms playing a major role in the aging process is the accumulation of oxidative damage in essential molecules such as in lipid membranes, proteins, DNA, more particularly mitochondrial DNA. One of the important consequences of the accumulation of this damage is, in particular, a reduction in the cell's capacity to produce ATP. In fact, with age damage to the mitochondrial DNA accumulates (Bechnan et al, Ann NY Acad Sci, 854: 118-27, 1989). This phenomenon causes an increase in the oxidative stress of the cells as well as a reduction in the amount of intracellular energy (Porteous et al, Eur J Biochem 1998, 257 (1): 192-201).

Thus, reducing the concentration of ATP in the cell induces significant problems. Indeed, DNA synthesis decreases, as does the synthesis of proteins essential for the proper functioning of the skin, such as matrix proteins extracellular or keratin. The decrease in ATP synthesis also has the direct consequence of a decrease in cell proliferation and differentiation.

In addition, it has been shown (O. Toussain et al, Exp Gerontol, 1995; 30 (1): 1-22) that the production of cellular energy can be considerably destabilized when the cell is under stress, which accelerates the aging process. Indeed, the cell subjected to stress will use a large part of its energy in response to this stress. The ability to respond to a stimulus as well as the ability to counteract stress, processes which require energy, will be considerably reduced in an aged cell or in a cell subjected to photoaging. Thus, the phenomenon of cellular aging is related to the stress that the cell undergoes but also to the process of producing energy necessary for the cell to follow, as well as to perform the various functions necessary for cell differentiation.

Health and cosmetic professionals have for many years been looking for means to combat or, at least, to reduce the phenomena of skin aging, as well as means to increase the resistance of the skin to external aggressions and to stress she experiences daily. A certain number of substances introduced into cosmetic or pharmaceutical products have emerged, but there is still progress to be made in order to be able to have cosmetic or pharmaceutical products capable of resolving these problems in a satisfactory manner.

The technical problem to be solved was therefore, for the inventors, to find a new substance, cosmetically or pharmaceutically acceptable, which is capable of combating both the phenomenon of skin aging and of protecting the skin in an effective manner so that it does not undergo the degradations caused by aggressions and stresses of external origin.

The inventors have succeeded in selecting particular substances having remarkable properties when these are applied to the skin. Thus, unexpectedly, the inventors have discovered that the association of certain molecules, such as the association of diacylglycerol and fatty alcohol, has remarkable properties and, in particular, that it helps to prevent the phenomena of skin aging. and that it protects the skin. The Applicant has notably discovered a composition which has an effect on the modulation of the concentration of ATP in the cell, on the intracellular concentration of calcium as well as on the production of proteins essential to the skin.

Indeed, this composition makes it possible to significantly increase the intracellular concentration of ATP and the concentration of calcium. The cell can therefore effectively fight against all stress phenomena and prevent the manifestations of aging.

To the knowledge of the applicant, it has never been described in the prior art the use of a composition containing the combination of diacylglycerol and fatty alcohol, as active principle, in cosmetics and / or in dermatology and / or in pharmaceuticals.

A remarkable property of the combination according to the invention is that it has greater effects than those which are reasonably expected due to the simple addition of the effects of each of the components constituting the composition.

One of the advantages of this invention is therefore to allow the use of each of the components of the composition in proportions lower than what is generally common to use.

Thus, according to a first aspect, the subject of the present invention is a cosmetic and / or dermatological and / or pharmaceutical composition comprising, as active principle, at least the combination of at least one diacylglycerol and at least one fatty alcohol. By diacylglycerol, according to the invention, is meant the compounds of formula (I):

(I) CH ₂ - 0 - C (0) - R CH ₂ - 0 - C (O) - R

I

CH - 0 - C (0) - R 'or CH- OH

I I

CH ₂ - OH CH ₂ - 0 - C (O) - R '

wherein R and R 'represent the aliphatic chain of a fatty acid; this fatty acid having a carbon chain whose carbon number is between 12 and 26. Preferably according to the invention, the groups R and / or R ′ have a carbon chain with 16, 17 or 18 carbon atoms. That is to say that the constituent fatty acids of diacylglycerol will consist of 16 to 18 carbon atoms.

The groups R and R ′ can be linear or branched carbon chains and / or saturated or unsaturated, the number of unsaturation being between 1 and 6. The groups R and R ′ can also be mono- or poly- chains hydroxylated, and / or mono- or poly-methoxylated, and / or mono- or poly-oxidized, and / or mono- or poly-epoxylated. In summary, the R and R 'groups can be in the different forms naturally present in fats.

Preferably according to the invention, the diacylglycerol present in the composition is 1,2 - diacylglycerol of formula:

CH ₂ - O - C (0) -R

I

CH - O - C (0) -R * |

CH ₂ - OH

Diacylglycerols (DAG) are compounds that are widely studied, among other things, for their marker properties. They play a fundamental role, in particular by the action they exert on a protein kinase C, and thus have a cellular activator function.

DAGs exist in the form of several isomers: 1,2-DAG and 1,3-DAG. These isomers have different origins; indeed, the 1,2-DAG isomer is attributed to an incomplete synthesis of triglycerides (glycerol esters with three fatty acids, TG), in particular in vegetable oils; while the 1,3 isomers are due to an enzymatic or chemical hydrolysis of the triacylglycerols (during the oil extraction process for example).

The DAGs according to the invention are preferably 1,2-DAGs. These DAGs are obtained from triglycerides, compounds representing the most common form of lipid reserve in the body, they are, in fact, the most important constituents of fat.

The reaction method, used according to the present invention in order to obtain the DAGs, can be a chemical reaction carried out in an acid or alkaline medium such as, for example, a hydrolysis of the fatty materials consisting of triglycerides. This hydrolysis can also be carried out enzymatically, such as, for example, a biochemical reaction which uses a hydrolase such as a lipase.

The DAG constituting the association according to the invention can be obtained from different types of fat. The fats concerned in the present application can be animal, vegetable or synthetic oils, composed of triglycerides, glycerol triesters and / or fatty acids. By way of example, mention may be made of animal fatty substances, tallow, fish oils. We can also cite the original oils vegetable, such as, for example, olive oil, rapeseed oil, soybean, corn, palm, macadamia or even sunflower oil, cottonseed oil, linseed oil, castor oil, safflower oil, sweet almond oil etc. These oils can also be chemically modified oils by transesterification or any other process which preserves the structure of the glycerol triesters.

Preferably, the DAGs used in the present invention are obtained from triglycerides having undergone enzymatic hydrolysis, in particular by lipases, in order to result in 1,2-DAG.

Lipases are enzymes that hydrolyze glycerol esters. Several types of lipase are determined according to their different level of reaction rate. These enzymes can also be classified into several groups, according to their different specificities: specificity with respect to the substrate; position specific or regioselective; specificity with respect to the nature of fatty acids or typoselectivity; specificity with respect to a position or stereospecificity. Certain lipases have no specific specificity. Others are regioselective: thus, for example, pancreatic lipase and lipases of microbial origin, aVAspergillus or Rhysopus, are lipases 1,3. Regioselective lipases are in common industrial use both in the fat industry and in detergents. Other lipases are stereospecific such as Candida lipase which has a sn2 type stereospecificity. The nomenclature sn determines the positions snl, sn2 and sn3 of the triglyceride skeleton according to the configuration of the asymmetric carbon presented in Fisher projection

In the present invention, a stereospecific snase type sn3 is preferably used. This lipase thus hydrolyzes the triglycerides, preferably forming 1,2-diacylglycerol. The lipase used can be of plant (Carica papaya) or microbial (Penicellium cyclopium) origin. According to a preferred embodiment of the invention, the hydrolysis of the triglycerides is carried out with a lipase from Carica papaya (Villeneuve et al. JAOCS, 72, 6: 753.1996).

Fatty alcohols are aliphatic alcohols with a long hydrocarbon chain having a single hydroxyl function in the terminal position. By a fatty alcohol is meant the compounds of formula (II):

(II) R "- OH in which R "represents the aliphatic chain of a fatty alcohol. This fatty alcohol being constituted by a carbon chain comprising from 10 to 34 carbon atoms.

According to a particular embodiment of the invention, the fatty alcohols have a carbon chain whose carbon number is between 12 to 26. According to another preferred embodiment of the invention, the fatty alcohol has on its chain aliphatic between 16 and 22 carbon atoms.

Thus, these fatty alcohols will preferably be chosen from the group consisting of fatty alcohol with an aliphatic chain of medium size, saturated or unsaturated. Furthermore, the aliphatic chain of fatty alcohols, that is to say the group R ″, can be a linear or branched carbon chain and / or saturated or unsaturated, the number of unsaturation being between 1 and 6. The group R ″ can also be a mono- or poly-hydroxylated chain, and / or mono- or poly-methoxylated, and / or mono- or poly-oxidized, and / or mono- or poly-epoxylated. It can thus be present in all existing natural forms.

These fatty alcohols are found in large quantities in waxes. These waxes can be of animal origin, such as for example beeswax, of vegetable origin, such as jojoba, carnauba, candellila wax, or even of mineral origin.

Thus, for example, the controlled hydrolysis of the wax of jojoba oil (wax which constitutes more than 96% of jojoba oil) has the effect of releasing the main aliphatic fatty alcohols contained in it, this which makes it possible to obtain a mixture of fatty alcohols, with a saturated or unsaturated linear hydrocarbon chain.

In particular, the hydrolysis of jojoba oil makes it possible to obtain a mixture of fatty alcohols of a high degree of purity comprising, in their aliphatic chain, between 16 and 22 carbon atoms. This hydrolysis thus makes it possible to concentrate all the active principles which are capable of acting on the skin.

More generally, it is possible to obtain fatty alcohols from hydrolysis followed by a reduction of any fatty acid. Thus, the fatty alcohols according to the invention can be obtained from fatty acids. According to a preferred embodiment of the invention, the fatty alcohols will be obtained from waxes. According to another advantageous embodiment of the invention, the fatty alcohols may be derived from vegetable oils. The most common oils consist of fatty acids having from 12 to 26 carbon atoms in their aliphatic chain, most often they are fatty acids comprising between 16 and 18 carbon atoms, these fatty acids can be saturated or unsaturated. The lipid extract thus hydrolyzed and reduced will lead to fatty alcohols having, on their aliphatic chain, groups comprising from 12 to 26 carbon atoms.

The fatty alcohols according to the invention will preferably be obtained from a hydrolysis of the waxes present in jojoba oil (Simmondsia chinensis). This hydrolysis makes it possible to release the fatty alcohols constituting this wax. This hydrolysis can be carried out chemically in an alkaline or acid medium. In the case of alkaline hydrolysis, the fatty alcohols, making up the so-called unsaponifiable fraction, will be conventionally recovered by extraction with a solvent immiscible with water. The hydrolysis of these waxes can also be carried out enzymatically.

A particularly advantageous possibility of the process for obtaining the combination according to the invention consists in carrying out this operation simultaneously with the hydrolysis of the triglycerides generating the diacylglycerols and using the same lipase.

Preferably according to the invention, the active ingredients constituting the combination, that is to say the diacylglycerol and / or the fatty alcohols, will be of vegetable origin, that is to say that they will be obtained from raw material of plant origin. Thus, according to a preferred embodiment of the invention, the diacylglycerols can be obtained from oil of vegetable origin, such as for example olive oil. The fatty alcohols will also come from plants, in particular vegetable waxes. Thus, preferably, the fatty alcohols according to the invention can be obtained from constituent waxes of vegetable oils, such as, for example, Jojoba oil. According to the invention, the term "active principle can be defined as being any molecule or any set of molecules capable of bringing about modifications or modulations in the functioning of a biological system.

According to a particular embodiment of the composition of the invention, the association will be carried out in particular proportions. Thus, the amount of diacylglycerol will represent between 0.1 and 99% of the association, the fatty alcohol possibly being present in amounts representing between 0.01 and 30% of the total weight of the mixture constituting the association. Preferably, diacylglycerol will represent between 55 and 95% of the association, the fatty alcohol will be present in amounts representing between 3 and 20% of the total weight of the association.

Of course, the effective quantity of active principle corresponds to the quantity necessary in order to obtain the desired result. According to an advantageous embodiment of the invention, the diacylglycerol of formula

(I) mentioned above is present, in the pure state, in the compositions of the invention in an amount representing from 10 ^"6 % to 20% of the total weight of the composition, and preferably in an amount representing from 10 ^{" 3} % at 1% of the total weight of the final composition.

According to another advantageous embodiment of the invention, the aforementioned fatty alcohol of formula (II) is present, in the pure state, in the compositions of the invention in an amount representing from 10 ^"6 % to 10% the total weight of the composition and preferentially in an amount representing from 10 ^"4% to 1% of the total weight of the final composition.

According to an advantageous embodiment of the invention, the abovementioned active compounds are dissolved beforehand or dispersed in one or more cosmetically or pharmaceutically acceptable solvents such as water, ethanol, propanol or isopropanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, vegetable oil or any mixture of these solvents.

According to yet another advantageous embodiment of the invention, the abovementioned active compounds are dissolved beforehand in a cosmetic or pharmaceutical carrier such as liposomes or adsorbed on powdery organic polymers, mineral supports such as talcs and bentonites, and more generally dissolved in, or attached to, any cosmetically or pharmaceutically acceptable carrier. According to another advantageous embodiment of the cosmetic or dermatological or pharmaceutical composition according to the invention, the composition will contain between 60 and 95% of an excipient which will be, for example, petroleum jelly or any other fatty substance which will allow good solubilization of aforementioned active compounds. Preferably, the composition will contain between 80 and 90% of this excipient. By above-mentioned active compounds is meant the compounds as defined above, that is to say the diacylglycerol of formula (I) and the fatty alcohols of formulas (II), or any mixture or preparation containing them. The composition according to the invention can be a cosmetic or dermatological or pharmaceutical composition. Preferably according to the invention, the composition is a cosmetic composition, because it is intended to improve the appearance and the general cutaneous performance of the individual who uses it. The composition according to the invention is preferably a cosmetic and / or dermatological composition suitable for administration by the topical skin route comprising a cosmetically or pharmaceutically acceptable medium.

It is obvious that the invention is intended for mammals in general and more particularly for human beings. Whatever the form of the invention, the composition according to the invention can be ingested, injected or applied to the skin (on any cutaneous zone of the body), the hair, the nails or the mucous membranes. Depending on the mode of administration, the composition according to the invention can be in all the galenical forms normally used.

Preferably, the compositions according to the present invention will be in a dosage form suitable for administration by the topical skin route, and cover all cosmetic or dermatological forms. These compositions must therefore contain a cosmetically acceptable medium, that is to say compatible with the skin, hair or hair.

These compositions may in particular be in the form of an aqueous, hydroalcoholic or oily solution; an oil-in-water, water-in-oil or multiple emulsion; they can also be in the form of creams, suspensions, or even powders, suitable for application to the skin, mucous membranes, lips and / or hair.

These compositions can be more or less fluid and have the appearance of a cream, a lotion, a milk, a serum, an ointment, a gel, a paste or a foam.

They can also be in solid form, such as a stick or be applied to the skin in the form of an aerosol. They can be used as a care product and / or as a make-up product for the skin.

For injection, the composition according to the invention can be in the form of an aqueous, oily lotion or in the form of serum. For application to the eyes, the composition can be in the form of drops and for ingestion, it can be in the form of capsules, granules, syrups or tablets. These compositions also include any additive commonly used in the intended field of application as well as the adjuvants necessary for their formulation, such as solvents, thickeners, diluents, antioxidants, dyes, sunscreens, self-tanning agents, pigments, fillers, preservatives, perfumes, odor absorbers, cosmetic or pharmaceutical active ingredients, essential oils, vitamins, essential fatty acids, surfactants, film-forming polymers, etc. .

In all cases, a person skilled in the art will take care that these adjuvants, as well as their proportions, are chosen so as not to harm the desired advantageous properties of the composition according to the invention. These adjuvants can, for example, correspond from 0.01 to 20% of the total weight of the composition.

When the composition of the invention is an emulsion, the fatty phase can represent from 5 to 80% by weight and preferably from 5 to 50% by weight relative to the total weight of the composition. The emulsifiers and co-emulsifiers used in the composition will be chosen from those conventionally used in the field under consideration. For example, they can be used in a proportion ranging from 0.3 to 30% by weight, relative to the total weight of the composition.

Of course, those skilled in the art will take care to choose any additional compounds, active or non-active, and / or their quantities, so that the advantageous properties of the mixture are not, or not substantially, altered by the addition considered.

The compositions according to the invention find application in particular as cosmetic or pharmaceutical compositions for the skin, mucous membranes and / or semi-mucous membranes. They find a very particular application as a product for protecting and / or caring for the skin, or even as an anti-wrinkle and / or anti-aging composition. One can also consider an application in the field of compositions for making up the skin of the face and the body, such as lipsticks, foundations, tinted creams, concealer sticks, or sunscreen compositions. or artificial tanning. The compositions which are the subject of the invention find their application in a large number of treatments, in particular cosmetic or dermatological treatments, and they can constitute a cosmetic composition, in particular for the treatment, protection, care, removing makeup and / or cleansing the skin, lips and / or hair, and / or for making up the skin, lips, eyelashes and / or body.

The composition according to the invention may also consist of solid preparations also comprising soaps or cleaning bars. The composition can also be packaged in the form of an aerosol composition also comprising a propellant under pressure. The composition can also be for oral use, for example a toothpaste paste. The composition of the invention can also be a cosmetic composition intended for oral administration. For administration by the oral route, the composition according to the invention can be in any suitable form, particularly in the form of an oral solution, a syrup, a tablet, a dragee, a capsule, or a nutritional supplement.

According to the invention, it is possible, among other things, to add to the composition of the invention other active agents intended in particular for the prevention and / or treatment of the cutaneous manifestations of aging and / or for the protection of the skin against external aggressions.

A subject of the invention is also the use, as active ingredient, of the combination of at least one diacylglycerol compound of formula (I) and of at least one fatty alcohol of formula (II), in or for the preparation of a composition, the combination or the composition being intended to treat, curatively and / or preventively, the cutaneous signs of aging as well as to improve the appearance of the skin and / or integuments.

More generally, the composition according to the invention will have an effective activity in all skin care and / or appendages. By the care of the skin and / or appendages, is meant all the actions intended to preserve or restore a good functioning of the skin and / or appendages or still any means which is used to preserve or improve their appearance and / or their appearance. Thus the treatment includes hydration, soothing, protection against all types of aggression, in particular sun protection, the fight and prevention of the manifestations of aging, in particular the skin manifestations of aging. The expression “cutaneous manifestations of aging” means any modification of the external appearance of the skin due to aging, such as, for example, wrinkles and fine lines, withered skin, soft skin, thinned skin, lack of elasticity and / or of skin tone, dull and dull skin but also all internal modifications of the skin which do not systematically result in a modified external appearance such as, for example, all internal degradations of the skin consecutive to a exposure to ultraviolet radiation. By the expression "improving the appearance of the skin" is meant all the phenomena which are likely to result in a visual improvement in the condition of the skin. The skin will look better; it will, for example, be much more beautiful, firm and / or smooth. All small imperfections will be diminished or removed. The papery appearance of the skin will, for example, be reduced.

It has been observed that the combination according to the invention has numerous actions at the level of the skin, in particular that it makes it possible to combat the phenomena of skin aging and that it makes it possible to protect the skin against all types of attack. exterior. Thus, the combination according to the invention can be intended to protect keratinous substrates, and more particularly to protect the skin and / or the integuments against all types of external aggressions.

The use of this mixture, or of a composition containing it, will allow the keratinous substrates to be protected and to better resist the stress that the environment produces on them. The term "external aggression" means the aggressions that the environment can produce. These attacks can be of chemical, physical, biological or thermal origin. By way of example, mention may be made of aggressions such as pollution, UN, friction, water with a high concentration of limestone, temperature variations or even products with an irritant nature such as surfactants, preservatives or the perfumes. The combination of compounds according to the invention makes it possible to increase the synthesis of intracellular ATP of the skin cells (in particular the fibroblasts and the keratinocytes). This increase in ATP concentration is very beneficial to the cell because the concentration of intracellular ATP is closely linked to all the phenomena of skin aging and cell stress. Another subject of the invention therefore is the use of the combination as defined above, or of a cosmetic composition comprising it, in order to increase the synthesis of intracellular ATP in skin cells and, in particular, that of fibroblasts of the dermis.

Tests have also shown that the combination, as defined above, makes it possible to increase the concentration of intracellular calcium. The compounds according to the invention can therefore also be used with the aim of increasing the intracellular calcium concentration of the skin cells, which makes it possible to activate various mechanisms favorable to the cell to help it fight against stress and aging. These compounds therefore have a favorable action at the level of the energy metabolism of skin cells, as well as a cytostimulatory activity. They are advantageously used as a care and treatment agent for the skin and / or the integuments making it possible to activate cellular energy metabolism. The term agent for activating cellular energy metabolism means, for example, compounds capable of increasing the synthesis of intracellular ATP in skin cells or also capable of increasing the concentration of intracellular calcium. Indeed, it has been demonstrated that the compounds according to the invention make it possible to increase the synthesis of intracellular ATP; but also that they are capable of causing an increase in the concentration of intracellular calcium of the skin cells. This stimulation makes it possible to activate various mechanisms favorable to the cell, in particular in order to help it fight against stress and aging. The combination according to the invention can also have an antioxidant action.

Numerous properties of the composition according to the invention have been demonstrated. Indeed, as experiments demonstrate in the examples, the combination according to the invention has beneficial effects on the synthesis of proteins of the extracellular matrix. Another subject of the invention therefore is the use, as active ingredient, of the combination of at least one diacylglycerol compound of formula (I) and of at least one fatty alcohol of formula (II), in or for the preparation of a composition, the combination or the composition being intended to increase the synthesis of proteins of the extracellular matrix.

By proteins of the extracellular matrix is meant, for example, proteins such as collagen, fibronectin or even elastin. More particularly, the combination according to the invention makes it possible to significantly increase the synthesis of fibronectin. Likewise, the association has been shown to have beneficial effects on protein synthesis in keratinocytes. Another subject of the invention therefore is the use of the combination, as active ingredient, of at least one diacylglycerol compound of formula (I) and of at least one fatty alcohol of formula (II), in or for the preparation of a composition, the combination or the composition being intended to increase the synthesis of keratins.

The combination according to the invention therefore has an effective action on the skin barrier, the combination according to the invention therefore increases the skin barrier function of the skin. In addition, it thus promotes tissue regeneration. Another subject of the invention is therefore the use, as active ingredient, of the combination of at least one diacylglycerol compound of formula (I) and of at least one fatty alcohol of formula (II), in or for the preparation of a composition, the combination or the composition being intended to promote cell differentiation, and more particularly, cell differentiation of skin cells. In addition, the combination or the composition according to the invention may be used in order to increase tissue regeneration and / or scarring of the skin.

Furthermore, the invention also relates to the use, as active ingredient, of the combination of at least one diacylglycerol compound of formula (I) and of at least one fatty alcohol of formula (II), in or for the preparation of a composition, the combination or the composition being intended to treat the manifestations of inflammation and skin irritation. The composition is, in fact, very well suited to the care of sensitive and fragile skin.

These various properties can be used in particular for producing compositions intended to protect the skin against external aggressions caused in particular by the action of solar radiation or by other physical, chemical or biological agents, or alternatively compositions making it possible to combat the aging of the skin, allowing it to be maintained and cared for.

According to another aspect, the present invention relates to a cosmetic treatment method for treating skin, in particular aged skin and / or for combating the phenomena of cellular aging, consisting in applying to the surface of the skin an effective amount of the composition such as previously defined in order to obtain the desired action. The present invention also relates to a cosmetic treatment process in order to protect the skin and / or the integuments against all types of external aggressions. According to another aspect of the invention, the present invention relates to a cosmetic treatment method in order to promote cell differentiation and / or to promote tissue regeneration and / or to reinforce the skin barrier of the skin and / or integuments.

Particular embodiments of this cosmetic treatment process also result from the preceding description. The cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the technique of usual use of these compositions, for example: application of creams, gels, serums, lotions, milks, shampoos or anti-sun compositions, on the skin or on the hair, or else, application of toothpaste on the gums.

Other advantages and characteristics of the invention will appear better on reading the examples given by way of illustration and without limitation.

Example 1 - Preparation of a composition containing 1,2-diacylglycerol and fatty alcohols of vegetable origin.

A - The mixture can be prepared in two distinct stages, then by combining, by simple mixing, the products resulting from these two processes in adequate proportions.

DAGs are prepared from a kilogram of olive oil and a quantity of water, or buffer solution, representing from 1% to 200% of the volume of the oil (preferably 150%). In a thermostatically controlled tank, this mixture is maintained at a temperature between 30 and 70 ° C, preferably at a temperature of 50 ° C. The pH is between 4 and 9, it is preferably equal to 7.5. This mixture is kept stirring in the presence of a lipase from Carica papaya, the amount of which is between 0.5 and 30% of the volume of oil used. The amount of useful enzyme depends on the degree of purity of the lipase used. The reaction is possible with raw papaya juice, however it is preferable to use a preparation purified from this juice after solubilization in an aqueous medium, stored in a polyol or lyophilized.

Stirring and temperature are maintained for a period of between one and six hours, that is to say for a time sufficient for the amount of diacylglycerol formed to be maximum. The reaction is monitored by determining conventional indices in the fat industry (such as, for example, acid and hydroxyl indices) and by using chromatographic methods for determining the concentration of diacylglycerol.

The hydrolyzed oil can then be used as it is, however the total hydrolysis of the triglycerides to diacylglycerols is, most often, not complete. The reaction medium therefore consists mainly of unprocessed triglycerides, free fatty acids, monoglycerides and type 1, 2 and 1,3 diacylglycerols. It is therefore preferable to purify this oil in order to increase the content of type 1,2 diacylglycerol. Conventionally free fatty acids can be removed in the form of soap by washing with a solution basic aqueous. The other compounds are separated using precipitation, distillation or industrial chromatography techniques.

The fatty alcohols are prepared by hydrolyzing an amount of one kilogram of jojoba oil in the presence of five volumes of 2M ethanolic potash. The hydrolysis takes place at reflux, for a period of two to four hours. When the reaction is complete, twenty liters of water are added to the reaction mixture.

The fraction containing fatty alcohols is extracted three times with two liters of hexane, dichloromethane or tert-butyl methyl ether. The organic fractions are subsequently combined and then evaporated. Then collected about 400 grams of a yellow oil consisting of more than 90% fatty alcohols.

In a last step, for example, one volume of the preparation containing the fatty alcohols is mixed for 20 volumes of the preparation containing the DAGs, as obtained above. A composition is then obtained containing, approximately, 80% of 1,2-DAG and 20% of fatty alcohol. B - Another possibility of preparing the mixture constituting the composition according to the invention is to produce simultaneously, in the same process, DAGs and fatty alcohols.

DAGs and fatty alcohols are prepared from 1 kg of olive oil and 250 g of jojoba oil. The hydrolysis of this mixture is carried out in the same manner as for the DAGs, that is to say in the same manner as above.

The mixture of oil and hydrolyzed waxes can then be used as it is, however the total hydrolysis of the triglycerides and of the wax is, most often, not complete. The reaction medium therefore consists mainly of unprocessed triglycerides, fatty alcohol and fatty acid monoglycerides, and type 1, 2 and 1,3 diacylglycerols. It is therefore preferable to purify this oil in order to increase the content of type 1,2 diacylglycerols and fatty alcohols. The other compounds can, in the same way as previously, be separated by means of precipitation, distillation or industrial chromatography techniques.

This gives a mixture essentially containing 1,2-diacylglycerol and fatty alcohols.

Example 2 - Demonstration of the effect of the association of 1, 2-diacylglycerol and a fatty alcohol on the synthesis of ATP. The aim of this study is to determine the influence of the association of 1,2-diacylglycerol and a fatty alcohol on the production of ATP by skin cells. This study is carried out using a Kit: "ATP Bioluminescence Assay Kit HS II", which makes it possible to assess the level of intracellular ATP. Fibroblasts and human HaCat cells were cultured and then cultured in 12-well plates. When the cells have reached 60% confluence, solutions containing 0.3% of the preparation of Example 1 were applied to the cells for periods of 5, 15 and 30 minutes, control tests were carried out in applying solutions containing no active ingredient to the cells. At the end of the incubation time, the plates are emptied, then rinsed with cold PBS then 250 μL of a lysis buffer, provided by the kit, are added. The cells are then harvested and each well is rinsed with 500 μL of cold PBS. A dilution to l / 1000th is made for each condition, with cold PBS, before each reading. The ATP assay is carried out on these samples: 50 μL of this dilution are deposited in a cuvette and 50 μL of luminol are added. After 10 seconds, the luminescence reading is triggered. The measurements are carried out using a device: the Biocounter M2010A LUMACΘ / 3M.

The results express the percentage increase in luminescence, measured after 15 minutes of incubation, in the cells treated with the active agents compared to the untreated cells. This increase in luminescence expresses the increase in the amount of intracellular ATP, the luminescence being proportional to the amount of ATP present in the cells.

These results demonstrate that in the presence of the combination of the two active agents, the amount of intracellular ATP increases significantly compared to cells not treated with the active agents. Example 3 - Demonstration of the effect of the association of 1,2-diacylglycerol and a fatty alcohol on the amount of intracellular calcium.

The objective of this test is to demonstrate the influence of the association of 1,2-diacylglycerol and a fatty alcohol on the amount of calcium present in skin cells. This study is carried out using the confocal fluorescence imaging technique and using specific probes which allow the amount of intracellular calcium to be assessed.

Fibroblasts were cultured and then cultured in culture dishes of diameters 35. When the cells have reached 70% confluence, solutions containing 0.3% of the preparation of Example 1 are applied to the cells, control tests were carried out by applying a solution containing no active ingredient to the cells.

The probe used to detect calcium is the Fluo-4 AM probe (F-14217). These probes have the property of expressing a fluorescence of increasing intensity during their binding with calcium. The Fluo-4 probe is incubated for 20 minutes at a rate of 5 μL to 1 mM in 1.5 ml of medium containing the cells. The cells are rinsed with 2 ml of medium, then they are put under the microscope. A basal state is measured for a few seconds and then a solution containing active agents, or a control solution not containing any, is added. Recordings are made by confocal microscopy every 6 seconds. The active ingredients are added after 3 stimulations which record the basal rate, then every 6 seconds for 15 minutes.

The results obtained are presented in FIG. 1. FIG. 1 illustrates the result of the fluorescence measurements (in pixels), on 4 cells, as a function of time (in seconds). They demonstrate that, on the selected cells, a significant increase in fluorescence intensity is observed one minute after the addition of the active agents. This increase in intensity reflects the increase in the amount of intracellular calcium. This intensity peak is absent in the cells tested with the solution containing no active agent.

These results thus demonstrate that the combination of 1,2-diacylglycerol and a fatty alcohol has a positive action on the amount of intracellular calcium. This association therefore makes it possible to increase the amount of calcium in the skin cells.

Example 4 Demonstration by immunofluorescence of the effect of the association of 1,2-diacylglycerol and a fatty alcohol on the expression of fibronectin. The aim of the study is to determine the influence of the association of 1,2-diacylglycerol and a fatty alcohol on the synthesis of fibronectin, by fibroblasts, by the immunofluorescence technique.

Immunofluorescence is a semi-quantitative technique which makes it possible to assess the level of each of the proteins present in the cell cytoplasm.

Human fibroblasts are seeded in Lab-teks® and then cultured overnight. After aspiration of the medium, a composition containing 0.3% of the combination of 1,2-diacylglycerol and a fatty alcohol as defined in Example 1, or a control composition not containing the active agents, is added. The cells are then incubated for 24 h. After removal of the supernatants and rinsing of the cultures, the cells are fixed with methanol for 4 minutes at 4 ° C. and then rinsed with PBS buffer. 200 μL of anti-fibronectin antibodies are then added. The incubation lasts 2 hours at room temperature. The supernatants are eliminated and the cells are rinsed with PBS. 200 μL of secondary antibodies, coupled to a fluorescent marker (fluorescein) are then added. After 1 hour of incubation at room temperature, the supernatants are eliminated and the cells are rinsed with PBS. The slides are then mounted and then examined under the Epi-fluorescence microscope. The amounts of fibronectin, synthesized by the cells, are proportional to the intensity of the fluorescence.

The results obtained demonstrate that the addition of the association of these active agents in the culture medium of fibroblasts has the effect of increasing the synthesis of fibronectin by the cells. This stimulation has been observed significantly. In fact, when the fibroblasts are incubated in the presence of the composition containing the active agents, there is after 24 hours an increase in the intensity of the fluorescence thus translating a stimulation of the synthesis of fibronectin by the fibroblasts.

Example 5 - Demonstration by immunofluorescence of the association of 1,2-diacylglycerol and a fatty alcohol on the expression of keratins.

The aim of the study is to determine the influence of the association of 1,2-diacylglycerol and a fatty alcohol as obtained in Example 1 on the synthesis of keratins, by keratinocytes, by the technique immunofluorescence.

A study by the immunofluorescence technique, identical to that of Example 4, was carried out on human HaCat keratinocytes, with anti-keratin antibodies Pan cK. The results obtained demonstrate that the addition of the association of 1,2-diacylglycerol and a fatty alcohol in the culture medium of keratinocytes has the effect of increasing the synthesis of keratin by the cells. This stimulation has been observed significantly. In fact, when the keratinocytes are incubated in the presence of the composition containing the active agents, there is, after 24 hours, an increase in the intensity of the fluorescence thus translating a stimulation of the synthesis of keratin by the keratinocytes.

Example 6 Preparation of Compositions

1 - Day cream (oil-in-water emulsion):

Phases A and B were heated to a temperature between 75 and 80 ° C. Phase A was emulsified in B, then phase C was added after cooling from 30 ° C. 2 - Night cream (water-in-oil emulsion 1

Phases A and B were heated to a temperature of 75 and 80 ° C. Phase B was emulsified in A with stirring, then the mixture was cooled to 40 ° C by intense stirring. Then phase C was added and the cooling was continued, with stirring, to ambient temperature. Phase D was then introduced at a temperature below 30 ° C.

Claims

1. Cosmetic and / or dermatological and / or pharmaceutical composition comprising, as active principle, in a physiologically acceptable medium, at least the combination of a diacylglycerol of formula (I):

(I) CH ₂ -OC (0) -R CH ₂ -0-C (0) -R

I I CH-O-C (0) -R * or CH-OH

I I

CH ₂ -OH CH ₂ -0-C (0) -R '

wherein R and R 'represent the aliphatic chain of a fatty acid having a carbon chain whose carbon number is between 12 and 26; and at least one fatty alcohol of formula (II):

(II) R "- OH

wherein R "represents the aliphatic chain of a fatty alcohol having a carbon chain whose carbon number is between 10 to 34.

2. Composition according to Claim 1, characterized in that the diacylglycerol is 1,2 - diacylglycerol of formula:

CH ₂ -0-C (0) -R

I

CH -0-C (0) -R '

I CH ₂ -OH

3. Composition according to claim 1 or 2 characterized in that the groups R,

R 'and / or R "are linear or branched aliphatic chains; and / or saturated or unsaturated, the number of unsaturation being between 1 and 6; and / or mono- or poly-hydroxylated; and / or mono- or poly-methoxylated; and / or mono- or poly-oxidized; and / or mono- or poly-epoxylated.

4. Composition according to any one of claims 1 to 3 characterized in that the groups R and / or R ', have on their carbon chain 16, 17 or 18 carbon atoms.

5. Composition according to any one of the preceding claims, characterized in that the fatty alcohols have a carbon chain comprising from 12 to 26 carbon atoms, preferably from 16 and 22 carbon atoms.

6. Composition according to any one of the preceding claims, characterized in that the diacylglycerol of formula (I) and / or the fatty alcohol of formula (II) are of vegetable origin.

7. Composition according to claim 6 characterized in that the diacylglycerol of formula (I) is obtained from an oil of vegetable origin, and in particular from olive oil.

8. Composition according to claim 6 or 7 characterized in that the fatty alcohol of formula (II) is obtained from oil of vegetable origin, and in particular from jojoba oil.

9. Composition according to any one of the preceding claims, characterized in that the diacylglycerol is present in proportions representing between 0.1 and 99% and the fatty alcohol in proportions representing between 0.01 and 30% of the total weight of the mixture constituting the association; preferably diacylglycerol represents between 55 and 95% and fatty alcohol between 3 and 20% of the total weight of the association.

10. Composition according to any one of the preceding claims, characterized in that the diacylglycerol of formula (I), in the pure state, is present in an amount representing from 10 ^"6 % to 20% of the total weight of the composition, preferably in an amount representing from 10 ^"3 % to 1% of the total weight of the final composition.

11. Composition according to any one of the preceding claims, characterized in that the fatty alcohol of formula (II), in the pure state, is present in an amount representing from 10 ^"6 % to 10% of the total weight of the composition, and preferably in an amount representing from 10 ^{" 4} % to 1% of the total weight of the final composition.

12. Composition according to any one of the preceding claims, characterized in that it is in the form of a cosmetic and / or dermatological composition suitable for administration by the topical cutaneous route, for the skin, the mucous membranes and / or the integuments, comprising a cosmetically or pharmaceutically acceptable medium.

13. Composition according to any one of the preceding claims, characterized in that the active compounds are dissolved beforehand or dispersed in one or more cosmetically or pharmaceutically acceptable solvents such as water, ethanol, propanol or isopropanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, vegetable oil or any mixture of these solvents.

14. Composition according to any one of the preceding claims, characterized in that the active compounds are dissolved beforehand in a cosmetic or pharmaceutical carrier such as liposomes or adsorbed on powdery organic polymers, mineral supports such as talcs and bentonites, and more generally solubilized in, or attached to, any cosmetically or pharmaceutically acceptable carrier.

15. Composition according to any one of the preceding claims, characterized in that it is in the form of an aqueous, hydroalcoholic or oily solution or in the form of an oil-in-water, water-in-oil emulsion or multiple emulsions or in the form of cream, suspensions, or even powders; these compositions possibly being more or less fluid or solid and having the appearance of a cream, a lotion, a milk, a serum, an ointment, a gel, a paste, foam or stick.

16. Use of the combination of at least one diacylglycerol of formula (I) and of at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or composition being intended to treat, curatively and / or preventively, the cutaneous signs of aging, and / or to improve the appearance of the skin and / or appendages

17. Use of the combination of at least one diacylglycerol of formula (I) and of at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or the composition being intended to protect the skin and / or the integuments against external aggressions, and / or to reinforce the cutaneous barrier of the skin.

18. Use of the combination of at least one diacylglycerol of formula (I) and of at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or the composition being intended to increase the synthesis of proteins of the extracellular matrix.

19. Use according to claim 18, characterized in that the combination or the composition are intended to increase the synthesis of fibronectin.

20. Use of the combination of at least one diacylglycerol of formula (I) and at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or composition being intended to increase the synthesis of keratin.

21. Use of the combination of at least one diacylglycerol of formula (I) and of at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or the composition being intended to increase the synthesis of ATP in the skin cells.

22. Use of the combination of at least one diacylglycerol of formula (I) and of at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the association or the composition intended to increase the concentration of intracellular calcium in skin cells.

23. Use of the combination of at least one diacylglycerol of formula (I) and at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or the composition being intended to promote tissue regeneration and / or scarring of the skin.

24. Use of the combination of at least one diacylglycerol of formula (I) and at least one fatty alcohol of formula (II), as defined in claims 1 to 9, as active ingredient, in or for the preparation of a composition; the combination or composition being intended to increase cell differentiation of skin cells.

25. Cosmetic treatment method for treating aged skin and / or for combating the phenomena of cell aging and / or for protecting the skin and / or the integuments against all types of external aggressions and / or for promoting cell differentiation and / or to promote tissue regeneration and / or to reinforce the barrier of the skin and / or integuments consisting in applying to the surface of the skin and / or integuments an effective amount of the composition as defined according to claims 1 to 14.