FR2953714A1 - Cosmetic use of N,N'-diarylmethylene ethylenediaminediacetic acid ester compounds as agent for preventing a reduction and/or reinforce the barrier function of the skin - Google Patents

Abstract

Cosmetic use of at least one N,N'-diarylmethylene ethylenediaminediacetic acid ester compounds (I) or their salts as agent for preventing a reduction and/or reinforce the barrier function of the skin, is claimed. Cosmetic use of at least one N,N'-diarylmethylene ethylenediaminediacetic acid ester compounds of formula (I) or their salts as agent for preventing a reduction and/or reinforce the barrier function of the skin, is claimed. R1 : linear saturated 1-6C alkyl or branched saturated 3-6C alkyl; R2-R4 : H or -OR5; and R5 : H, linear saturated 1-5C alkyl or branched saturated 3-5C alkyl. [Image] ACTIVITY : Dermatological. MECHANISM OF ACTION : None given.

Description

The present invention relates to the cosmetic use of at least one N, N'-diarylmethylene ethylenediaminediacetic acid ester as an active ingredient for improving the barrier function of the skin. It relates more particularly to the use of such an asset for the prevention and / or treatment of cutaneous dryness (and in particular dry skin) and / or cutaneous dryness related to menopause.

Human skin consists of two compartments, namely a deep compartment, the dermis, and a superficial compartment, the epidermis. The dermis provides the epidermis with a solid support. It is also its nurturing element. It consists mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance called the fundamental substance, components synthesized by the fibroblast. There are also leucocytes, mast cells or tissue macrophages. It also contains blood vessels and nerve fibers. The epidermis is in contact with the external environment. Its role is to protect the body from dehydration and external aggressions, be they chemical, mechanical, physical or infectious. The natural human epidermis is composed mainly of three types of cells which are the keratinocytes, a very large majority, the melanocytes and the Langerhans cells. Each of these cell types contributes by its own functions to the essential role played by the skin in the body. The cells constituting the epidermis are delimited by a lipid domain. During differentiation, the phospholipids whose role consists in elaborating the fluid structure of the cell membranes of the living layers of the epidermis, are gradually replaced by a mixture consisting for the most part of fatty acids, of cholesterol and of sphingo lipids. These lipids are organized into specific lamellar structures whose integrity depends not only on the quality of the fractions present but also on their respective proportions. This lamellar lipid structure of the lipid domain of the epidermis is responsible for the fluidity and therefore the suppleness of the skin.

Lipids are also responsible for the barrier properties of the epidermis, particularly the stratum corneum. Epidermal lipids are synthesized mainly in the living epidermis. They consist mainly of phospholipids, sphingolipids, cholesterol, free fatty acids, triglycerides, cholesterol esters and alkanes. As can be seen from the following, all of these lipids have an essential role in the skin and it is important to guarantee their integrity. Thus, phospholipids are essential for the constitution of cell membranes. They play an important role in the mediation of extracellular signals and the formation of free aliphatic chains used for energy production. They constitute a reservoir of free fatty acids necessary for the constitution of sphingolipids. Sphingolipids (or ceramides) are essential for maintaining the multilamellar structure of intercorneocyte lipids. They are also essential for water exchanges and the barrier function of the epidermis.

Cholesterol plays a key role in skin hydration and in the "barrier" function of the epidermis. As for free fatty acids, they play a major role in maintaining the lamellar structure of the lipids of the stratum corneum, as well as in the constitution of cell membranes where they are responsible for the membrane fluidity but also physiological processes such as the functioning of receptors or enzymatic activity. In addition, the lipids of the epidermis also have an influence on the activity of certain enzymes involved in the maturation and desquamation of the stratum corneum. Changes in the level or type of lipids present in the stratum corneum therefore influence the barrier function of the stratum corneum, the water content and the condition of the skin.

However, in certain situations, whether skin aging, actinic aging, dietary imbalance, repeated external aggressions, physical or chemical (such as UV, pollution, wind, cold, air conditioned) or psychological factors (fatigue, stress), the human epidermis may have qualitative or quantitative changes in its composition and / or lipid synthesis. For example, at menopause, the main changes in the dermis cause in the menopausal woman a thinning of the skin and / or mucous membranes. The woman then feels a sensation of "papery skin" or "skin that pulls" and there is an accentuation of fine lines and wrinkles surface. The skin has a rough appearance on palpation and reduced flexibility. It also takes on the appearance of dry skin. It is therefore important to be able to stimulate or modulate the lipid synthesis of the skin to maintain or restore their integrity to enable them to fulfill their biological function ensuring the good condition of the skin. In order to improve the lipid content of the epidermis, two courses of action are conceivable. The first is the exogenous supply of lipid compounds topically. The second is to stimulate the synthesis of endogenous lipids. It has thus been demonstrated on epidermis constructed in vitro that it is possible to improve the lipid profile of reconstructed epidermis by adding ascorbic acid (vitamin C) in the culture medium (J. Invest Dermatol. 109: 348-355, 1997). For obvious reasons, there remains a need for novel agents to improve skin barrier function, including via the stimulation of endogenous lipid synthesis. The inventors have discovered, unexpectedly, that certain esters of N, N'-diarylmethylene ethylenediaminediacetic acid could be used as such. Esters of N, N'-diarylmethylene ethylenediaminediacetic acid are already described in WO 94/11338 as iron chelators and scavengers against the formation of hydroxyl free radicals. However, these compounds have never been described so far for their action on epidermal lipogenesis and for the improvement they could provide to the barrier function of the skin.

The invention thus relates, according to one of its aspects, to the cosmetic use of an effective amount of at least one compound of general formula (I): N (I) in which: each group R1 and R "I represents independently a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 6 carbon atoms or a branched saturated alkyl radical comprising from 3 to 6 carbon atoms, provided that the two groups R 1 and R "1 do not simultaneously represent a hydrogen atom, - R2, R3 and R4 represent, independently of each other, a hydrogen atom or a radical -OR5, and - R5 represents a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 5 carbon atoms or a branched saturated alkyl radical comprising from 3 to 5 carbon atoms, or their salts, as an agent for preventing a decrease in and / or reinforcing the barrier function of the skin. It may in particular be a use of a compound of general formula (I) as defined previously as an agent for preventing a decrease in and / or reinforcing the barrier function of the skin in order to improve the hydration of the skin. skin and / or to improve the retention of water in the skin. As is apparent from the following, the compounds of general formula (I) according to the invention have an effect on epidermal lipogenesis. They make it possible more particularly to stimulate, on the one hand, the synthesis of polar lipids and to orient, on the other hand, the synthesis of the total epidermal lipids towards the less polar lipid classes in connection with the later stages of keratinocyte differentiation. Consequently, the compositions containing them are particularly well suited to improving the barrier function of the skin, which itself allows a better water retention in the skin.

Thus, the compounds of general formula (I) above can be used as such as a moisturizing agent of the skin. According to one embodiment, the compounds of general formula (I) according to the invention can be used to prevent and / or treat dry skin. According to another embodiment, the compounds of general formula (I) according to the invention can be used to prevent and / or treat cutaneous dryness related to menopause. In particular, the compounds of general formula (I) according to the invention are particularly effective in preventing and / or treating skin dryness conditions, and in particular the state of acquired and / or constitutional dryness of the skin.

They thus make it possible to prevent and / or significantly limit the dehydration of the skin. They are particularly effective for preventing and / or treating dry skin, and even more particularly for dry skin and / or dry constitutional skin.

In the case of acquired dryness of the skin, the intervention of external parameters such as exposure to chemical agents, difficult climatic conditions or solar rays is crucial. Under these outside influences, the skin can become momentarily and locally dry.

The present invention also relates, in another of its aspects, to a cosmetic skin treatment method for preventing a decrease in and / or reinforcing the barrier function of the skin, comprising the administration of at least an effective amount of at least one compound of general formula (I) as defined above.

According to one embodiment, it may be a cosmetic treatment method for preventing and / or treating dry skin.

According to another embodiment, it may be a cosmetic treatment method for preventing and / or treating cutaneous dryness related to menopause. By "effective amount" is meant in the sense of the present invention an amount sufficient to achieve the expected effect.

For the purposes of the present invention, the term "prevent" means decreasing the risk of occurrence of a phenomenon. For the purposes of the invention, the expression "to prevent a decrease in the skin barrier function" means to prevent any alteration of said barrier function to below its level of natural efficacy and which would have the consequence of initiating the manifestation of one or more skin disorders as described above. As indicated above, the compounds of general formula (I) considered according to the invention make it possible to ensure the maintenance of the barrier function of the skin at its level of normal efficiency, that is to say the level at which it ensures its function of protecting the body.

For the purposes of the invention, the expression "reinforcing the barrier function of the skin" means improving the barrier function of the skin. This improvement is particularly decisive when the barrier function of the skin is impaired and it is necessary to restore it. This deterioration of the skin may especially be due to a state of dryness as described above.

It may also be advantageous when it is desired to consolidate the native barrier function of the skin, in order to confer in particular on the body a better resistance to external aggressions against which it is likely to be exposed. According to one embodiment, the use or the process according to the invention may comprise the application of a compound of general formula (I) according to the invention by the topical route. Topically, is meant an administration of a compound of general formula (I) according to the invention or compositions containing by application to the skin. For the purposes of the invention, the terms "cosmetic use" and "cosmetic treatment method" respectively describe the uses and treatment methods as being nontherapeutic.

ESTER OF N, N'-DIARYLMETHYLENE ETHYLENE DIAMINEDIACETIC ACID The esters of N, N'-diarylmethylene ethylenediaminediacetic acid considered according to the invention are compounds of general formula (I): R 3 in which: each group R 1 and R "I independently represents a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 6 carbon atoms or a branched saturated alkyl radical containing from 3 to 6 carbon atoms, provided that the two groups R 1 and R" l do not simultaneously represent a hydrogen atom, - R2, R3 and R4 represent, independently of each other, a hydrogen atom or a radical -OR5, and - R5 represents a hydrogen atom or a saturated alkyl radical linear one comprising from 1 to 5 carbon atoms or a branched saturated alkyl radical comprising from 3 to 5 carbon atoms. These compounds can be obtained by any method known to those skilled in the art and, for example, according to the preparation methods described in WO 94/11338. (I) According to a first embodiment, it is more particularly N, N'-diarylmethylene ethylenediaminediacetic acid esters of general formula (Ia): R3 in which: - RI represents a linear saturated alkyl radical comprising of 1 to 6 carbon atoms or a branched saturated alkyl radical comprising from 3 to 6 carbon atoms, - R2, R3 and R4 represent, independently of each other, a hydrogen atom or a radical -OR5, and - R5 represents a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 5 carbon atoms or a branched saturated alkyl radical comprising from 3 to 5 carbon atoms. According to one embodiment, R2, R3 and R4 represent a hydrogen atom. According to another embodiment, R1 denotes an isopropyl radical. It may especially be the compound of general formula (Ia) in which R 2, R 3 and R 4 represent a hydrogen atom and R 1 denotes an isopropyl radical, that is to say the diisopropyl ester of the N, N'-bis- (benzyl) ethylenediamine-N-N'-diacetic acid of formula: This compound is more particularly described in Example 16 of WO 94/11338. According to a second embodiment, it may also be esters of N, N'-diarylmethylene ethylenediaminediacetic acid of general formula (Ib): R3 (Ib) in which: R1 represents a linear saturated alkyl radical comprising of 1 to 6 carbon atoms or a branched saturated alkyl radical comprising from 3 to 6 carbon atoms, - R2, R3 and R4 represent, independently of each other, a hydrogen atom or a radical -OR5, and - R5 represents a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 5 carbon atoms or a branched saturated alkyl radical comprising from 3 to 5 carbon atoms. The compounds of formula (Ib) are novel compounds not described in the prior art. The invention also relates to such compounds. As the compound of formula (Ib), mention may be made of isopropyl monoester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid. The compounds of formula (Ib) can be obtained according to scheme I of synthesis by reacting a dibenzylated ethylenediamine (A) with a molar equivalent of tert-butyl bromoacetate in the presence of a base such as, for example, potassium carbonate in a polar solvent such as for example dimethylformamide, then reacting a molar equivalent of the bromoacetate derived from the alcohol R1OH. The intermediate diester (B) obtained is then selectively hydrolyzed to its tert-butyl part in an acid medium (for example, hydrochloric or trifluoroacetic acid) to yield the half-ester of formula (Ib).

NH 0 Br, 11.0 Br ...,) J ... O-R 1 R 3 R 3 R 2. R 2 R 2 R 3 R 3 R 1 R 4 R 3 HN base, solvent R 2 R 4 1. 2. R 4 R 2 R 3 (A) (B) Scheme I The salts of compounds (I), (Ia) and (Ib) previously described include conventional toxicants of said compounds such as those formed from organic or inorganic acids. By way of example, mention may be made of the salts of mineral acids, such as sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid and boric acid. Mention may also be made of organic acid salts, which may comprise one or more carboxylic acid, sulphonic acid or phosphonic acid groups. It may be linear, branched or cyclic aliphatic acids or aromatic acids. These acids may furthermore comprise one or more heteroatoms chosen from O and N, for example in the form of hydroxyl groups. These include propionic acid, acetic acid, trifluoroacetic acid, terephthalic acid, citric acid and tartaric acid. The preferred salts are those obtained from hydrochloric, sulfuric, acetic, trifluoroacetic, tartaric and citric acids.

According to the invention, the compound of general formula (I), (Ia) or (Ib), in particular of formula (Ia) can be used in a proportion of 0.005 to 5% by weight, in particular of 0.01 at 2% by weight, and more particularly from 0.01 to 1% by weight relative to the total weight of a composition containing it.

GALENIOUE The composition of the invention may be in any galenical form normally used for topical application, especially in the form of an aqueous, hydroalcoholic or oily solution, an oil-in-water or water-in-oil emulsion. or multiple, an aqueous or oily gel, a liquid anhydrous product, pasty or solid, an oil dispersion in an aqueous phase using spherules, these spherules may be polymeric nanoparticles such as nanospheres and nanocapsules or, better, lipid vesicles of ionic and / or nonionic type. This composition may be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a mousse . It can optionally be applied to the skin in the form of an aerosol. It may also be in solid form, in particular in the form of a stick for the lips when it is for example intended to treat labial fissures. It can be used as a care product and / or as a make-up product for the skin. In a known manner, the composition of the invention may also contain the usual adjuvants in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers, filters, pigments, odor absorbers and dyestuffs The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase, into the lipid vesicles and / or into the nanoparticles. In any case, these adjuvants, as well as their proportions, will be chosen so as not to harm the desired properties of the combination of assets according to the invention. When the composition of the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition: emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration. The emulsifier and the coemulsifier are present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

As oils that may be used in the invention, mention may be made of mineral oils (vaseline oil), vegetable oils (avocado oil, soybean oil), synthetic oils (perhydrosqualene) and silicone oils (cyclomethicone) ) and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (carnauba wax, ozokerite) can also be used as fats. As emulsifiers and coemulsifiers that can be used in the invention, mention may be made, for example, of fatty acid and polyethylene glycol esters such as PEG-20 stearate, and fatty acid and glycerin esters such as glyceryl stearate. . As hydrophilic gelling agents, mention may in particular be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, it is possible to mention mention modified clays such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes. As active agents, use may especially be made of keratolytic and / or desquamating agents, depigmenting agents, UV-screening agents, anti-free radical agents and mixtures thereof. In the event of incompatibility, at least some of the active ingredients may be incorporated into spherules, in particular ionic or nonionic vesicles and / or nanoparticles (nanocapsules and / or nanospheres), so that the incompatible ingredients between them are isolated from each other in the composition.

The invention will be better understood and its advantages will emerge more clearly, in the light of the following examples, which are given by way of illustration and without limitation. EXPERIMENTAL PART Effect of diisopropyl ester of N, N'-bis- (benzol) ethylenediamine-N-N'-diacetic acid with respect to the synthesis of polar lipids by monolayer keratinocytes. The cells selected for this study are spontaneously immortalized keratinocytes (human keratinocyte cells, HaCaT, Bukamp et al., 1988, J. Cell Biol., 106: 761-771). The maintenance conditions of HaCaT cells are those recommended by N. Fusenig et al. in DMEM medium (CaCl 2 mM) + 10% FCS. The evaluation tests carried out were carried out in a DM-SFM medium. This medium is characterized by a low CaCl 2 (0.15 mM) and an absence of fetal calf serum (FCS) or bovine pituitary extracts (BPE). The mitogenic component is provided by the addition of a cocktail defined in specific growth factors of the keratinocyte; this characteristic makes it possible to overcome the variability of the batches of serum and / or BPE during the deprivation of the mitogenic component which is a necessary step for the study of the proliferative processes.

The keratinocytes (HaCaT line) are cultured under two conditions: complete defined culture medium (standard condition) and culture medium depleted in growth factors. This depleted environment leads to a controlled delay in cell proliferation and metabolism. Under these conditions, it is then possible to measure the effects of compounds capable of compensating for the deficiency in growth factors of the culture medium and thus to revive cell multiplication and / or to stimulate their metabolism, in particular the synthesis of polar lipids (phospholipids glycosyl ceramides). Three biological markers are measured on the same cell population: the proportion of DNA that is proportional to the number of cells (Cyquant probe), the rate of polar lipid constituents of cell membranes (Red Nile probe) and mitochondrial respiration, which reflects the general cellular metabolism (XTT probe). The determination of the mitochondrial respiration (XTT test, ROCHE Cell Proliferation Kit II) and the DNA content (Cyquant test, MOLECULAR PROBES Cell Pro liferation Assay Kit C-7026) were performed according to the instructions given by the Suppliers. The determination of the polar lipid content was evaluated according to the procedure provided by N. Billoni & B. Buan (SdV-CCZ). The diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid is evaluated in effect at 1 and 5 μM, the contact time with the cells is 72 hours at 37. ° C under 5% CO2 in humid atmosphere. The positive control of the test is HBEGF, a growth factor of the keratinocyte. The results are expressed in% relative to the control. The results are as follows. Control Active 1 μM Active 5 μM DMSO HB-EGF Tester probe 100% ± 5 87% ± 9 99% ± 7 105% ± 6 223% ± 5 Cypress probe Red 100% ± 10 117% ± 8 167% ± 4 101% ± 11 320% ± 2 Nil XTT probe 100% ± 9 89% ± 8 82% ± 11 100% ± 7 257% ± 3 Diisopropyl ester of N, N'-bis- (benzyl) ethylenediamine-N acid -N'-diacetic demonstrates its ability to activate the synthesis of polar lipids by keratinocytes, when they are grown in depleted growth factor medium, a culture condition that significantly delays their metabolism and growth. It is effective from 1 .mu.M and progresses in efficiency to 5 .mu.M. The DMSO vehicle has no effect. The diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid thus induces a significant stimulation of the synthesis of polar lipids according to a dose effect, without affecting the other parameters. simultaneously measured on the same cell population as mitochondrial respiration (XTT probe) and cell growth (Cyquant probe). The activity of the diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid therefore seems to be specifically oriented towards the synthesis of polar lipids. These polar lipids, such as phospholipids, major components of the cell membranes, will be able to deliver during the epidermal differentiation free fatty acids and / or ceramides which will reinforce the lipid composition of the stratum corneum.

Effect of diisopropyl ester of N, N'-bis- (benzyl) ethylenediamine-N-N'-diacetic acid on epidermal lipogenesis by the reconstructed epidermis Episkin: This study is carried out by measurement the incorporation of radioactively labeled acetate in models of reconstructed human epidermis, whose total lipid composition is close to that of the human epidermis. Treatment and marking of the epidermis: The reconstructed epidermis and their culture medium are provided by EPISKIN SNC (Lyon, France). Upon receipt at J = 6 of culture, the reconstructed epidermis are grown in test medium (differentiation medium without Vitamin C) in 12-well plates. After incubation, the epidermides are treated or not (control) with diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid at 30 and 50 μM in the culture medium during 24 hours. The epidermides are then treated under the same conditions and the medium is supplemented with 14C radiolabeled acetate at a rate of 0.75 μCi / well) ([2-C acetic acid sodium, Amersham CFA14, 58mCi / mmol]) for 48 hours. Treatments are made in triplicate (3 epidermis per condition). Analysis of the incorporated radioactivity: The epidermis are washed in PBS buffer and then lysed by treatment with 0.5M perchloric acid on ice. The lipids are then extracted with a solution of methanol / chloroform (2: 1) and separated by addition of PBS buffer and chloroform after neutralization according to the procedure described by Bligh and Dyer (Bligh EG, Dyer WJ, a rapid method of total * id Extraction and Punfication, Can J Biochem Physiol, 1959, Aug; 37 (8) 911-7). The radioactivity incorporated in the organic phase (lipids) is quantified by liquid scintillation (LKB 1210 Rackbeta) after evaporation of the chloroform. The organic phases are dried under nitrogen, then the different lipid classes are separated by thin layer chromatography (Merck K60 plates) with the following solvent mixtures: for the phospholipids = chloroform / methanol / water (50: 18: 2.6 ) and neutral lipids = hexane / ether / acetic acid (15: 5.6: 0.19).

The different classes of lipids are quantified by direct counting of the radioactivity contained in the different spots on the chromatography plates using the Phospholmager Cyclone apparatus and the Multigauge software (Fujifilm). We are mainly interested in phospholipids, cholesterol, free fatty acids, ceramides and cerebrosides.

The results are as follows (expressed in% relative to the untreated control for each major class of lipids studied). Cholesterol Free fatty acids Phospholipids Ceramides and cerebrosides Treatment Mean% Average ~ 0 Mean% Mean% Intensity ~ 0 Intensity% Intensity ~ o Relative Intensity o relative control relative control relative control control Control 44024.5 100 16543 100 15941,7 100 32887 100 Acid N, N'-43204.7 98 20148.2 122 13036.9 82 36274.5 110 bis- (benzyl) ethylenediamine -N-N'-diacetic acid 30 μM acid N, N'-45504 103 20278 , 6 123 11710.3 73 33666.5 102 bis- (benzyl) ethylenediamine-N-N'-diacetic 50 μM On the reconstructed epidermis Episkin, and after 72 hours of contact, the diisopropyl ester of the acid N N, N'-bis- (benzyl) ethylenediamine-N-N'-diacetic tested at 30 and 50 μM increased the synthesis of free fatty acids required for the synthesis of ceramides. At 30 μM, it also slightly stimulated the synthesis of ceramides and cerebrosides, cerebrosides being precursors of ceramides. As a corollary, there is a smaller amount of phospholipids, major components of the cell membranes of the squamous epidermis, which disappear during epidermal differentiation in favor of apolar lipids constituting the intercellular cement of the stratum corneum. Diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid has no effect on cholesterol.

On reconstructed epidermis, the diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid shows its capacity to guide the synthesis of epidermal total lipids towards the less polar lipid classes. in connection with the later stages of keratinocyte differentiation, to strengthen or correct the lipid composition of the stratum corneum and thus enhance the natural hydration of the skin.

EXAMPLES OF COMPOSITION ACCORDING TO THE INVENTION These compositions are obtained by the usual techniques commonly used in cosmetics. Composition 1: Moisturizing Care Cream Beeswax 1.5% Apricot Almond Oil 13.0% Fragrance 0.4% Diisopropyl Ester 0.01% N, N'-bis- (Benzyl) ) ethylenediamine-N-N'-diacetic Xanthane 0.5% Cyclopentadimethylsiloxane 5.0% Sterilized demineralized water 69.29% Sucrose mono-di-palmitostearate 3.0% Methylglucose sesquistearate 3.0% Stearic acid 1.0% Cetyl alcohol 3.0% Preservatives 0.3% The composition applied daily on the face confers a good hydration of the skin.

Composition 2: Body Oil Vaseline Oil 47.99% Apricot Almond Oil 6.0% Perfume 1.0% Diisopropyl Ester of N, N'-bis- (benzyl) ethylenediamine-N-N 0.01% Diacetic Cyclopentadimethylsiloxane 45.0%

The oil applied to the body gives a good hydration of the skin.

Composition 3: make-up removing milk 2-ethyl hexyl palmitate 10.5% Liquid fraction of shea butter 16.5% Preservatives 0.3% Perfume 0.15% Diisopropyl ester of 25 N, N'-bis acid - (benzyl) ethylenediamine-N-N'-diacetic 0.01% Sodium hydroxide 0.04% Carboxyvinyl polymer 0.2% Demineralized sterilized water 69.8% Mixture of cetylstearylglucoside 30 and cetyl and stearyl alcohols 2.5 % This cleansing milk gives a good hydration to the skin cleansed.

Composition 4: Care cream Beeswax 1.5% Apricot almond oil 13.0% Preservatives 0.3% Fragrance 0.4% Triethanolamine 0.17% Diisopropyl ester of N, N acid Bis (benzyl) ethylenediamine-N-N'-diacetic 0.02% Xanthan 0.5% Cyclopentadimethylsiloxane 5.0% Demineralized sterilized water qs 100% Sucrose mono-di-palmitostearate 3.0% Methylglucose sesquistearate 3 The composition applied daily on the face confers good hydration of the skin.

Claims (11)

REVENDICATIONS1. Cosmetic use of an effective amount of at least one compound of the general formula (Ia): in which: RI represents a linear saturated alkyl radical comprising from 1 to 6 carbon atoms or a branched saturated alkyl radical comprising from 3 to 6 carbon atoms, R 2, R 3 and R 4 represent, independently of each other, a hydrogen atom or a radical -OR 5, and - R 5 represents a hydrogen atom or a linear saturated alkyl radical comprising from 1 to 5 carbon atoms or a branched saturated alkyl radical having 3 to 5 carbon atoms, or salts thereof, as an agent for preventing a decrease in and / or enhancing the barrier function of the skin. 2. Use according to claim 1, wherein R2, R3 and R4 represent a hydrogen atom. 20 3. Use according to any one of the preceding claims, wherein RI is an isopropyl radical. 4. Use according to any one of the preceding claims, wherein the compound of general formula (Ia) is diisopropyl ester of N, N'-bis (benzyl) ethylenediamine-N-N'-diacetic acid. 5. Use according to any one of the preceding claims, as a moisturizing agent of the skin. 6. Use according to any one of the preceding claims, for preventing and / or treating dry skin. 7. Use according to any one of the preceding claims, for preventing and / or treating cutaneous dryness related to menopause. 8. Use according to any one of the preceding claims, wherein said compound of general formula (Ia) is used in a proportion of 0.005 to 5% by weight, in particular 0.01 to 2% by weight, and more particularly from 0.01 to 1% by weight relative to the total weight of a composition containing it. 9. A cosmetic skin treatment method for preventing a decrease in and / or reinforcing the barrier function of the skin, comprising the administration of at least an effective amount of at least one compound of general formula (Ia) such as defined in claims 1 to 4. 10. Cosmetic treatment method according to the preceding claim, characterized in that it is intended to prevent and / or treat dry skin. 11. Cosmetic treatment method according to claim 9 or 10, characterized in that it is intended to prevent and / or treat cutaneous dryness related to menopause.