WO1998009611A1

WO1998009611A1 - Cosmetic use of compounds with lipoaminoacid structure and cosmetic compositions with soothing activity incorporating some of these compounds

Info

Publication number: WO1998009611A1
Application number: PCT/FR1997/001563
Authority: WO
Inventors: Corinne Stoltz; Nelly Michel
Original assignee: Societe D'exploitation De Produits Pour Les Industries Chimiques - Seppic
Priority date: 1996-09-09
Filing date: 1997-09-05
Publication date: 1998-03-12
Also published as: JP2000517335A; EP0925058A1

Abstract

The invention concerns the cosmetic use as soothing agent of an aminoacid N-acylated compound of general formula: (I) in which: R-CO represents one linear or branched alkyl radical having 12 carbon atoms, preferably one lauryl radical; R' represents the characterising chain of said aminoacid; of a salt of this compound or of a mixture of such compounds, or of their salts. The invention also concerns novel cosmetic compositions with soothing activity incorporating some of said compounds in particular associated with one mineral element or with known soothing compounds.

Description

COSMETIC USE OF LIPOAMINOACID STRUCTURED COMPOUNDS AND COSMETIC COMPOSITIONS WITH SOOTHING ACTIVITY INCORPORATING SOME OF THESE COMPOUNDS

The present invention relates to a new cosmetic use of compounds with a lipoamino acid structure, as well as cosmetic compositions with soothing activity incorporating some of these compounds.

The compounds with a lipoamino acid structure are N-acylated amino acid derivatives corresponding to the following general formula:

R— CO— NH— CH— COOH

10

R 'in which:

R generally represents the characterizing chain of a fatty acid, saturated or unsaturated, linear or branched, having from 3 to 30 carbon atoms; and R 'represents a characterizing chain of an amino acid.

The expression "characterizing chain" used in the context of the present application designates the non-functional main chain of the fatty acid or of the amino acid considered.

Thus, for a fatty acid corresponding to the general formula R-COOH, the characterizing chain will be the chain represented by R, while for an amino acid represented by the general formula HoN-CHR'-COOH, the characterizing chain will be the chain represented by R '.

The N-acylated amino acid derivatives are most often in the form of mixtures obtained by acylation of a mixture of pure amino acids or derived from the complete hydrolysis of proteins.

These proteins may be of animal origin, such as, for example, collagen, elastinc, keratin or casein, or alternatively of vegetable origin, such as in particular cereals, or oilseeds.

These lipoamino acid compounds are, because of their amphiphilic structure, particularly advantageous biological vectors as regulators of skin physiology and prove to be suitable for multiple applications, in particular in cosmetics.

The properties of these compounds generally follow from the nature of the fatty chains and the amino acids constituting them. The characterizing chains of palmitic acid (Cl 6) are generally known in the cosmetic field for their softening and emollient properties.

In addition to these known properties and due to the lipophilic nature of these chains (close to the nature of the skin) certain compounds with lipoamino acid structure synthesized from palmitic chains exhibit a soothing activity.

Thus, the product known under the trade name Lipacide® PVB (palmitoyl wheat aminoacids according to INCI designation) has a relatively high soothing activity.

A soothing product is capable of acting by various mechanisms, in particular by stimulating the natural defenses of the skin, by stimulating cell metabolism or by restructuring the skin barrier.

The characterizing chains of lauric acid (Cl 2) are, for their part, known in cosmetics for their surfactant properties which, a priori, are not compatible with soothing properties.

Thus, sodium lauroylglutamate and sodium cocoylglutamate have been described as gentle agents for cleaning the skin and mucous membranes. We know that these products are non-irritating to the skin. However, no document known to the Applicant suggests that such products would have a soothing activity capable of being curative.

By soothing activity is intended to designate within the framework of the present application any property of a product which, applied topically, makes it possible to help the skin curatively curb against stress caused by an external aggression of a chemical nature (use of cosmetic products containing various specific raw materials, delipidating effect due to the use of surfactant solutions, ctc ...), dc solar nature (irritation by exposure to ultraviolet rays, sunburn, etc.), or even mechanical nature (shaving irritation, hair removal, etc.).

In particular, soothing activity will be understood to mean any activity exercising with respect to the enzymes intervening during an inflammation and in particular with respect to the elastase. It has been discovered quite unexpectedly, and this constitutes the basis of the present invention, that compounds with a lipoamino acid structure comprising a fatty chain having 12 carbon atoms, preferably constituted by a lauroyl radical, exhibit an extremely soothing efficacy. interesting, and superior to that of compounds with a lipoamino acid structure whose fatty chain is a palmitic chain.

Thus, according to a first aspect, the present application aims to cover the cosmetic use as a soothing agent, of an N-acylated compound of an amino acid of general formula: R— O— NH— CH— COOH (I)

R 'in which:

R-CO represents a linear or branched alkyl radical having 12 carbon atoms, preferably a lauroyl radical;

R 'represents the characterizing chain of said amino acid; a salt of such a compound or a mixture of such compounds, or their salts.

A compound which in the pure state proves to be particularly useful in the context of the use in accordance with the invention is lauroyl glutamate, that is to say the compound of formula (I) above, in which R- CO represents a lauroyl radical and R 'represents the characterizing chain of glutamic acid.

However, mixtures of N-acylated amino acid compounds and more particularly the products of the acylation reaction with lauric acid or one of its acylating derivatives, of a mixture of pure amino acids or from the complete hydrolysis of proteins,

The salts of the compounds according to the invention are preferably the alkali metal salts, in particular the sodium and potassium salts. Generally, the term “salt” is intended to denote any salified form of the compounds of formula (I) with a neutralizing agent making it possible to adjust the pH between 3 and 8, preferably around 5, that is to say a pH close to that of the skin.

Among the neutralizing agents which can be used for this purpose, mention may, for example, be made of sodium or potassium hydroxide. The expression “acylating derivatives of lauric acid” is intended to denote here any derivative of lauric acid capable of leading by an acylation reaction with an amino acid or a mixture of amino acids to the compounds of formula (I ) above. Such derivatives are for example the symmetrical anhydride of lauric acid or preferably the chloride of lauric acid.

The lauric acid used in this context can be in a pure form or even come from a natural source consisting of a mixture of fatty acids, in which lauric acid is a major component. By majority component is meant a component representing at least 50% by weight of the mixture. Such a natural source can be, for example, a cocoyl or palmistoyl cut (from palm kernel oil).

Advantageously, the abovementioned acylating agent will consist of the chloride of lauric acid. Many amino acids are capable of being used in the context of the present invention.

By way of example, there may be mentioned glycine, serine, aspartic acid, glutamic acid, valinc, threoninc, argininc, lysine, proline, leucine, phenylalanine, isoleucinc , histidine, tyrosine, tryptophan, asparagine, hydroxyprolinc, hydroxylysine and omithine.

Amino acid mixtures particularly useful in the context of the present invention include mixtures of glutamic acid, glycine, alaninc and aspartic acid.

Another particularly suitable mixture is a mixture of alanine and glycine.

As other mixtures of amino acids which may be used, mention may be made of mixtures making it possible to reconstitute proteins such as soy proteins, sunflower, lupine, wheat, corn, potato, collagen, silk, keratin, etc. The acylation reaction allowing the compounds of formula to be obtained

(I) mentioned above can be carried out chemically in an alkaline medium (pH 8 to 10) according to the Schotten Bauman reaction or by enzymatic route and those skilled in the art may refer in particular to the reference Surfactant Science Series, volume 7, Anionic Surfactants, part II, chapter 16, pages 581 to 617 (Marcel Dekker - 1976).

The compounds thus obtained can optionally be purified by acidification (pH 0.5 to 3) and extraction in a solvent (isopropyl alcohol, toluene, etc.) or by precipitation in ice water and decantation.

The amino acids used as a mixture can be pure or result from the complete hydrolysis of proteins.

This hydrolysis can be carried out, for example, by heating at a temperature between 60 and 130 ° C. a protein placed in an acidic or alkaline medium.

This hydrolysis can also be carried out enzymatically with a protease, optionally coupled to an alkaline or acid post hydrolysis.

In general, a currently preferred embodiment for the preparation of the lipoamino acid compounds of formula (I) comprises the following steps:

- Acylation in an alkaline medium (pH 8 to 10) of an excess mixture of amino acids (extemporaneous mixture or obtained by complete hydrolysis of a protein) with a fatty acid (in the chloride or anhydride form).

The amino acid / acid chloride ratio is preferably 1.05 to 1.30 equivalents.

The optimal acylation temperature is around 80 ° C but varies from one amino acid to another between 60 and 110 ° C.

The duration of acylation depends on the equipment used (size, agitation); it is approximately 2 hours for an acylated mass of 500 kg and approximately 5 hours for an acylated mass of 5,000 kg.

- Breakage of the alkaline acylate by acidification to decant the water-soluble impurities and release the acid organic acylate (optimal pH 0.5 to 3 depending on the amino acids).

- Purification by washing with water or with the addition of clctctrolytcs or co-solvent to promote decantation.

The soothing properties of compounds with a lipoamino acid structure of formula (1) have been demonstrated by studying the anti-elastase activity in vitro of these compounds. This method has been used, insofar as it constitutes the most relevant and least costly method among the anti-enzyme methods known for this purpose.

The results obtained were verified in vivo on humans by an ultra-violet inflammation test.

It has been found that the soothing activity of the compounds of formula (I) is manifested at low concentrations, compatible with those which can be used in a cosmetic formulation for topical use.

Thus, these compounds can be used for the manufacture of a topical cosmetic composition with soothing activity, at a concentration by weight of between 0.1 and 5%, expressed relative to the total weight of the composition.

Such a cosmetic composition will usually be in the form of an aqueous solution, a single or multiple emulsion.

Such compositions can be, for example, oil-in-water or water-in-oil emulsions, such as creams, milks, lotions, wipes, make-up removers for the face or the eyes, etc.

Such compositions can also be deodorant products or foaming products such as in particular shampoos, shower gels, makeup removers, liquid soaps, etc. Advantageously, the compounds with lipoamino acid structure of formula

(I) will be used in combination with mineral elements, in particular mineral salts, and in particular potassium and magnesium.

It has in fact been observed that such minerals potcntialiscnt the soothing activity of compounds with a lipoamino acid structure of formula (1). Thus, according to a second aspect, the present application aims to cover a composition in particular cosmetic with soothing activity, characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— O— NH— H — COOH

R 'in which:

R-CO represents a linear or branched alkyl radical having 12 carbon atoms, preferably a lauroyl radical; R 'represents the characterizing chain of said amino acid; of a salt of such a compound, or of a mixture of such compounds, or of their salts, in combination with an effective amount of at least one mineral element, preferably chosen from potassium and magnesium. The expression "mineral element" used in the context of the present invention designates macro-elements or micro-elements, preferably in the form of salts with an organic or mineral anion (aspartates, gluconates, glycerophosphates, bidolates, sulfonates, etc. ).

Many minerals can be used in the context of the present invention and mention will be made in particular of potassium, magnesium, manganese.

Advantageously, the weight ratio between the compounds with a lipoamino acid structure and the mineral elements in these compositions will be between 1:50 and 1: 2.5. It has moreover been observed that the compounds with a lipoamino acid structure of formula (I) according to the invention potentiate the soothing activity of compounds known as soothing in the state of the art, such as in particular dipotassium glycyrrhizinate, or alpha bisabolol.

Thus, according to a third aspect, the present application aims to cover a composition in particular cosmetic with soothing activity, characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— O— NH— CH— COOH (I)

R ^* in which:

R 'represents the characterizing chain of said amino acid; a salt of such a compound, or a mixture of such compounds, or their salts, in combination with an effective amount of dipotassium glycyrrhizinate or alpha bisabolol. Advantageously, the weight ratio between the compounds with a lipoamino acid structure and the dipotassium glycyrrhizinate or the alpha bisabolol in its compositions will be between 4: 1 and 1: 4.

Finally, it has been demonstrated by an in vivo study that the compounds with a lipoamino acid structure of formula (I) according to the invention exhibit a particularly remarkable soothing activity vis-à-vis people with sensitive and reactive skin.

Thus, these compounds make it possible to reduce the neurosensitive sensations intimately linked to the state of sensitive skin. In particular, these products make it possible to reduce the intensity of tingling induced by the application of hydrophilic or lipophilic alpha-hydroxy acids (AHA), such as in particular lactic acid or octanoyl salicylate or other cosmetic active agents. like acidic vitamin A.

Thus, according to a fourth aspect, the present application aims to cover a cosmetic composition characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— CO— NH— H— OOH (1)

I

R 'in which:

R 'represents the characterizing chain of said amino acid; a salt of such a compound, or a mixture of such compounds, or their salts, in association with a cosmetic active principle capable of inducing neurosensitive reactions on the skin.

Such cosmetic active principles capable of inducing neurosensitive reactions on the skin are in particular vitamin A acid and alpha-hydroxy acids among which mention may be made of lactic acid, glycolic acid, salicylic acid, salicylic octanoyl.

Advantageously, the weight ratio between the compounds with a lipoamino acid structure and the cosmetic active principle capable of inducing neurosensitive reactions on the skin, in these compositions will be between 99/1 and 10/90. The present invention will be better understood on reading the following examples given only without implied limitation.

In these examples, and unless otherwise indicated, the percentages are expressed by weight. Example 1: Preparation of a composition based on compounds with lipoamino acid structure of formula (I) according to the invention.

To a mixture consisting of 27.4 kg of L-aspartic acid, 35.3 kg of L-glutamic acid, 7.9 kg of L-alanine, 7.9 kg of glycine and 112.5 kg of water 96 kg of potassium hydroxide solution (50%) are added in order to obtain a pH of approximately 10. A co-solvent facilitating subsequent acylation can also be added to this mixture.

The temperature of the mixture thus obtained is brought to 80 ° C., then 110 kg of lauroyl chloride are poured simultaneously with stirring. The reaction lasts 2 hours. The “acylated mass” of 465 kg thus obtained comprises a mixture of lauroylated amino acids, free amino acids and lauric acid, these compounds being in the form of potassium salt.

The mixture of compounds with a lipoamino acid structure can be extracted from this acylated mass in a very acid medium (pH of about 1) and in the hot state (90 ° C.) for example by implementing the following protocol:

- adjustment of the pH to a value of 1 by adding an appropriate quantity (approximately 125 kg) of 30% hydrochloric acid, at a temperature of approximately 80 ° C;

- Stirring of the mixture thus obtained 30 minutes at 90 ° C (temperature due to exotherm);

- decantation for 30 minutes (the compounds with a lipoamino acid structure remaining in the organic phase);

- withdrawal of acidic water which is rejected after neutralization to thereby eliminate the free non-acylated amino acids, the salt formed and the co-solvent; - washing of the supernatant organic phase with saline water (10%

NaCl);

- withdrawal of the aqueous phase;

obtaining an organic phase containing more than 70% by weight of the following mixture of compounds with a lipoamino acid structure of formula (I): . 27% lauroyl glutamic acid. Lauroyl aspartic acid 30%. Lauroyl lysine acid 6%. 8% lauroyl alanine acid as well as reaction residues, in particular. Lauric acid 15%. Water 10%

. 1% sodium chloride. Co-solvent (propylene glycol) 3%

Example 2: Example of formulation incorporating a mixture of compounds with a lipoamino acid structure of formula (I).

To 155 kg of the organic phase obtained in Example 1, the following compounds are added with stirring: - Propylene glycol: 100 kg;

- Tris (Tris hydroxymcthyl aminométhane or trométhamine): sufficient quantity to obtain a pH of approximately 5.0 to 6.0;

- Sepicide® HB: 2 kg;

- Water: 200 kg. The mixture thus obtained is filtered on a membrane filter (approximately 3 μ).

A liquid, stable, odorless and water-soluble formulation is thus obtained, the pH of which is approximately 5.7.

Example 3: Example of formulation associating a mixture of compounds with a lipoamino acid structure of formula H) and mineral elements

The following compounds are added to 150 kg of the organic phase obtained according to Example 1:

- Propylene glycol: 100 kg;

- Tris: sufficient quantity to obtain a pH of approximately 5.0 to 6.0; - Mixed aspartate of potassium and magnesium: 5 kg;

- Sepicide® HB: 2 kg;

- Water: 200 kg.

The mixture thus obtained is filtered on a pocket filter (approximately 3 μ). A liquid, stable, odorless and water-soluble formulation is thus obtained, the pH of which is approximately 5.7.

Example 4: Demonstration of the soothing activity of the compounds with lipoamino acid structure of formula (T1 according to the invention

The soothing activity of the compounds with a lipoamino acid structure of formula (I) was evaluated using the anti-elastase test in vitro. a Principle of the test:

We know that human leukocyte elastase (ELH) is involved in a large number of inflammatory pathologies. This enzyme is particularly capable of degrading many macromolecules such as fibrous elastin, certain types of collagen, proteoglycans, glycoproteins.

For this reason, human leukocyte elastase is one of the links in the chain of reactions accompanying an inflammation phenomenon. The blocking of this enzyme by an anti-elastase effect therefore makes it possible to prevent the degradation of the aforementioned molecules and therefore to inhibit the process of inflammation.

The anti-clastatic properties of a given product can be demonstrated by an in vitro test, carried out with a spectrophotometer, using a support substance capable of degrading by coloring, in contact with human leukocyte elastase.

Such a substance can be for example N-methoxysuccinyl-alanine-prolinc-valinc-para-nitroanilidc, normally colorless substance which liberates, by hydrolysis by human leukocyte elastase, a colored product, para-nitroalinine, whose kinetics d appearance can be followed by spectrophotometry at 410 nm.

The reaction is carried out in a spectrophotometer thermostatically controlled at 25 ° C., having a sample changer. All the kinetics are carried out at least three times, the mean and the standard deviation then being calculated for the three values obtained.

The presence of a molecule with anti-clastastic activity results in a limitation of the appearance of the colored product and the anti-elastatic effect can then be calculated relative to a control curve obtained in the absence of said molecule. There is thus a correlation between the percentage of inhibition of the appearance of the colored product by the test compound and the percentage of inhibition of human leukocyte elastase.

The percentage of inhibition thus calculated is also representative of the soothing activity of the test compound. b) Results obtained

The soothing activity of the products of Examples 2 and 3 was evaluated by the test described above and the results obtained are reported in Table (I).

The values of the percentage of inhibition induced by the constituents of the compounds with lipoamino acid structure tested have also been indicated in this table.

Product tested% active ingredient% inhibition

Aspartic acid 0.625% 0%

Glutamic acid 0.625% 0%

Alanine 0.625% 0%

Glvcinc 0.625% 0%

Lauric acid (C12) 0.625% 17% 0.02% 0%

Product of Example 2 0.02% 66%

Mixed aspartate (K. Mg) 0.025% 0%

Product of Example 3 0.02% 77%

Table 1

These results show the high level of anti-elastatic activity of the compounds with a lipoamino acid structure of formula (I).

These results also show the potcntialisation effect of this anti-elastatic activity exerted by the mineral elements, since the use of mixed aspartate of potassium and magnesium cn an amount of about 1% by weight leads to a relative gain d activity of about 16% (see example 3 compared to example 2).

The amino acids as well as the mixed potassium and magnesium aspartate tested alone do not exhibit anti-elastatic efficacy, even at high concentration. The lauric chain has limited efficacy at high concentration and no efficacy at low concentration.

Comparison of the anti-elastatic efficacy of the compounds with lipoamino acid structure of formula (I) according to the invention to that of other compounds with lipoamino acid structure, the fatty chain of which is a palmitic chain:

The anti-elastatic efficacy of the compounds with a lipoamino acid structure of formula (I) according to the invention was compared with that of other compounds with a lipoamino acid structure, the fatty chain of which consists of palmitic acid.

The compounds with a comparative lipoamino acid structure were obtained according to experimental protocols analogous to those described in Examples 1 to 3.

The results obtained are summarized in Table II

Table II

* DPHP: Dipalmitoylhydroxyproline, compound with lipoamino acid structure obtained by acylation by palmitic acid of hydroxy-4-proline

** PAOC: Mixture of compounds with a lipoamino acid structure obtained by acylation with palmitic acid of a mixture of amino acids composed of aspartic acid, glutamic acid, alanine and glycine, in the following proportions:. Glutamic acid 45%

. Aspartic acid 35%

. Alaninc 10%

. Glycine 10% *** PVB: Palmitoyl wheat amino acids (according to INCI designation)

**** PCO: Palmitoyl collagcn amino acid (according to INCI designation). The results obtained show the significant superiority of the anti-elastatic activity of the compounds with lipoamino acid structure of formula (I) according to the invention whose fatty chain is derived from lauric acid, with respect to analogous compounds whose fatty chain is derived from palmitic acid.

These results are completely unexpected given the known properties of the palmitic and lauric chains.

Evaluation of the soothing activity of SUU UHE lipoamino acid compounds in individualized form:

The anti-elastatic efficacy of the various compounds with a lipoamino acid structure constituting the mixtures of the products of Examples 2 and 3 was evaluated.

The results obtained have been collated in Table 111 below:

Product tested% active ingredient% inhibition

Lauroyl glutamate 0.02% 80%

Lauroyl aspartate 0.02% 55%

Laurovl alaninatc 0.02% 45%

Laurovl glycinate 0.02% 30%

LML * 0.02% 50%

LCO * * 0.02% 54%

Table 111 * LML: Lysine lauroyl methionate (according to INCI name) ** LCO: Lauroyl collagen amino acid (according to INCI name) These results show the extremely high anti-elastatic efficacy of lauroylglutamate.

The lauroylaspartatc, lauroylglycinatc and lauroylalaninatc have a relatively weak anti-elastatic activity, but still equivalent, or even superior to that of lipoamino acids whose fatty chain is constituted by a palmitic chain.

The LML and LCO products also have an anti-elastic efficacy but significantly lower than that of lauroyl glutamate and that of the complex product of Example 3. F. evaluation of the anti-elastatic efficacy of various binary mixtures of compounds with a lipoamino acid structure of formula (T1 according to the invention:

The anti-elastatic efficacy of various binary associations of compounds with a lipoamino acid structure of formula (I) has been studied, in particular with the aim of determining possible synergistic associations.

The results obtained have been collated in Table IV.

Product tested% active ingredient% inhibition

Lauroyl alaninate + 0.01% / 0.01% 42%

Lauroyl aspartate (additive effect = 50%)

(50/50 mix) (v / v)

Lauroyl aspartate + 0.01% / 0.01% 51%

Lauroyl glycinate (additive effect = 42.5%)

(50/50 mix) (v / v)

Laurov l aspartate + 0.01% / 0. () L% 69.4%

Lauroyl glutamate (additive effect = 67.5%)

(50/50 mix) (v / v)

Lauroyl glutamate + 0.01% / 0.01% 60.7% lauroyl glycinate (additive effect = 55%)

(50/50 mix) (v / v)

Lauroyl glutamate + 0.01% / 0.01% 59.5%

Lauroyl alaninate (additive effect = 62.5%)

(50/50 mix) (v / v)

Lauroyl glycinate + 0.01% / 0.01% 51%

Lauroyl alaninate (additive effect = 37.5%)

(50/50 mix) (v / v)

Table IV The results obtained demonstrate an original synergy between lauroylglycinatc and lauroylalaninatc, since a mixture of these two compounds has an anti-elastatic efficacy greater than the sum of the efficiencies of each of these constituents. Demonstration of the potentiating effect of the soothing activity of compounds with a lipoamino acid structure of formula (Y) by dipotassium glycyrrhizinate:

The anti-elastatic efficacy of known soothing compounds, namely dipotassium glycyrrhizinate and alpha bisabolol (natural or racemic), as well as their association with the product of Example 3, was evaluated.

The results obtained have been collated in Table V

Product tested% active ingredient% Inhibition

Dipotassium glycyrrhizinate 0.0625% 10%

0.02% 0%

Natural alpha bisabolol 0.0625% 0%

0.02% 0%

Racemic alpha bisabolol 0.0625% 0%

0.02% 0%

Product example 3 + dipotassium glycyrrhizinate 0.01% / .01% 66%

(50/50 mixture) (v / v) (additive effect = 32%)

Product example 3 + natural alpha bisabolol 0.01% / 0.01% 60%

(50/50 mixture) (v / v) (additive effect = 31.5%)

Product of Example 3 racemic bisabolol alpha 0.01% / o.υι% 69%

(50/50 mixture) (v / v) (additive effect = 31.5%)

Table V

These results show the superiority of the anti-elastatic activity of the compounds with a lipoamino acid structure of formula (1) with respect to the dipotassium glycyrrhizinate and the alpha bisabolol.

We also observe an original synergy between dipotassium glycyrrhizinate or alpha bisabolol and the product of Example 3.

Additional tests, the results of which are not reported here, have shown that this synergy is exerted over a wide range of concentrations. In particular, this synergistic effect is exerted for compositions in which the weight ratio between the compound (s) of formula (I) and the dipotassium glycyrrhizinate or the alpha bisabolol can be between 4: 1 and 1 : 4.

Example 5: Demonstration by an in-vivo test of the soothing effect of compounds with a lipoamino acid structure of formula (IV Principle of the test:

The soothing effect of the product of Example 3 formulated at 3% (base

SEPIGEL + LANOL 99) was evaluated on 5 people, after sun exposure. The soothing effect of the product of Example 3 was compared with that of a product known for its soothing properties, glycerrhetinic acid. This product was formulated at

1% on the same basis (SEPIGEL + LANOL 99) as the product of Example 3.

Protocol:

Irritation (redness) is induced following UVA + UVB irradiation (IDEM 3000 solar stimulator from AROUANTEC) on 3 skin areas of the back skin of each panelist (1 DEM = 1 erythematous dose minimum).

The products studied (3% product of Example 3; 1% glycerrhetinic acid) are applied immediately after irradiation and then after 12 hours. The soothing effect of the products studied is determined by the evaluation of the intensity of erythematous reactions obtained 24 hours after irradiation in the skin areas (evaluation of erythema by colorimetric measurement).

The statistical comparisons between the various cutaneous zones studied were carried out at the level of the parameter ΔE which translates the intensity of the erythematcusc reaction.

The calculation ΔE corresponds to the following formula: ΔE = [(Δa) ² + (Δb) ^{2 +} (ΔL) ² ] Results obtained: Variations in ΔE:

Control Products exposed 1% ac. glycerrhetinic 3% product of Example 3

24 hours 3.6 + 0.3 3.0 + 0.5 2.7 + 02. not significant / significant witness / witness

- 1% / witness - 25% / witness The formula containing 3% of the product of Example 3 reduces erythema, compared to the control zone by 25% (significant reduction) while the formula containing 1% of glycerrhetinic acid does not reduce erythema, compared to the control zone, only 16% (non-significant reduction). This test therefore not only demonstrates the curative soothing effect of the product of Example 3 formulated after irritation by UV rays, but also demonstrates that its efficacy is greater than that of a product known for its soothing properties, under the test conditions. selected.

Similar soothing results can be expected following chemical or mechanical irritation, at the curative or even preventive level.

EXAMPLE 6 Demonstration by an In Vivo Test of the Soothing Effect of Compounds with a Lipoamino Acid Structure of Formula (IV, cn Particularly on Persons with Sensitive and Reactive Skin. Principle of the Test

The soothing effect of the product of Example 3 formulated at 3% was evaluated on people with sensitive and reactive skin.

We know that sensitive skin appears as an authentic syndrome characterized by the association of neurosensitive signs (sensations of heating, itching and tingling) and redness.

The characteristic sensations of sensitive skin can be caused, for example by a topical application of an alpha-hydroxy acid (AHA) such as lactic acid and the responses obtained seem well correlated to the state of sensitive skin. Study protocol

This test was carried out on 10 volunteers with very sensitive skin.

Before the start of the test, panelists with "hypersensitive" skin are selected. This selection is made as follows:. a 10% solution of lactic acid in physiological saline is applied to the nasolabial folds,

. the tingling sensations are then evaluated immediately after application at the level of the two grooves, on the basis of a visual analog scale at 6 points. Once the persons thus selected, the following test is carried out:. a 10% lactic acid solution is applied to the two nasolabial folds (right and left) of each volunteer.

. the product of Example 3 formulated at 3% is applied as is, only once, as soon as the tingling induced by lactic acid appears.

. The intensity of the tingling is evaluated during the 5 minutes following the application in the area having received the lactic acid (control) and in the area treated with the product to be studied.

Result? obtained

The average intensity of tingling was determined, at each time of the test, by calculating the average of the individual data obtained on all of the volunteers.

Statistical analysis was carried out on the one hand, on the values obtained in the area treated with the product studied, cn comparison to the values acquired in the control area and on the other hand, on the differences calculated between the values obtained at a given time and those determined after the application of lactic acid (ie before the application of the product studied: time "0"), for each of the treated and control zones.

These results are reported in Table VI below:

PICTURE INTENSITY

PRODUCTS T "0" (before Immediate 10 sec after 30 sec after 1 min after 2.5 min 5 min after

TESTS application) ment after application application application after application application application

WITNESS

ACID 3.0ι0.4 2.6 0.3 2.5 ± 0.3 2.1 ± 0.3 2.1i0.2 1.6 + 0.3 0.6 * 0.2

LACTIC

PRODUCT 2.8-04 1 A: 0.5 1.0-0.4 0.6ι0.3 0.2; 0 1 0.2 * 0.1 0.1 * 0.1

FROM LΕX 3

Table VI

It follows from these results that: - the area treated with lactic acid (control area) causes a persistent tingling sensation up to 5 minutes. - The product of Example 3 allows a statistically significant decrease in the intensity of tingling, immediately after application, then during the following 5 minutes, compared to the control area.

The intensity of the tingling decreased by approximately 46% immediately after the application of the product of Example 3 and decreased the tingling by approximately 90% one minute later compared to the control zone.

Thus, the product of Example 3, after a single skin application, has a very clear, immediate and persistent anti-tingling effect on the sensations induced in the nasolabial fold by a 10% lactic acid solution in people with "hypersensitive" skin.

Associated with products inducing sensitive reactions (example of AHAs, such as for example lactic acid), the products according to the invention therefore make it possible to very clearly and significantly reduce these reactions.

Example 7: Example of cosmetic compositions incorporating compounds with a lipoamino acid structure of formula (I) according to the invention:

Alcohol-free soothing aftershave balm Product of Example 3 03.00%

LANOL® 99 (lsoπonyl isononanoatc-SEPPIC) 02.00%

Sweet almond oil 00.50%

SEPIGEL® 501 (copolymers of acrylamide / mineral oil / Cl 3- 14 Isoparaffin / polysorbate 85 SEPPIC) 03.00% Water qs 100% perfume 00.40%

SEPICIDE® HB (Phenoxyethanol / Methylparaben /

Ethylparaben / propylparaben Butyl paraben-SEPPIC) 00.30%

SEPICIDE® Cl (imidazolidinyl urea - SEPPIC) 00.20%

AHA cream for sensitive skin

Product of Example 3 03.00%

MONTANOV® 68 (cetaryl glucoside -SEPPIC) 07.00%

SCHERCEMOL® 1 l8 (isostearyl isostearate) 15.00% Water qs 75.50%

SEPIGEL® 305 (polyacrytamide / C13-14

Isoparaffin / Laureth-7 SEPPIC) 02.00%

Preservative 00.50%

Lactic acid 10% qs.pH = 5

AHA cream for sensitive skin

MONTANOV® 68 (cetaryl glucoside -SEPPIC) 05.00%

LANOL® 99 (isononyl isononanoate -SEPPIC) 10.00%

Product of Example 3 03.00%

Water qs 100%

Gluconic acid 01.50%

TEA 00.90%

SEPIGEL® 305 (polyacrylamide / C13-14

Isoparaffin / Laureth-7 SEPPIC) 01.50% SEPICIDE® HB (Phenoxycthanol / Methylparabcn /

Ethylparaben / propylparaben Butyl paraben - SEPPIC) 00.30%

SEPICIDE® CI (imidazolidinyl urea - SEPPIC) 00.20% perfume 00.40%

Soothing cream W / O

MONTANE® 481 (Sorbitan oleate / beeswax stearic acid -SEPPIC) 8.00%

PEG-45 Dodccylglycol copolymer 2.00%

LANOL® 2681 (caprylatc copra caprate-SEPPIC) 5.00%

Vegetable squalane 25.00%

Octyl paramethoxycinnamatc 3.00%

Product of Example 3 3.00% SEPICIDE® HB (Phenoxycthanol / Methylparabcn /

Ethylparaben / propylparaben Butyl paraben - SEPPIC) 1.00% Water qs 100%

Glycerin 5.00%

MgSO4 7:20 AM 00.70% fragrance 00.40% Soothing after-sun care

Product of Example 3 3.00% LANOL® 99 (isononyl isononanoate -SEPPIC) 10.00%

SEPIGEL® 305 (polyacrylamide / C13-14 Isoparaffin / Laureth-7-SEPPIC) 2.50%

Water qs 100%

SEPICIDE® HB (Phenoxyethanol / Methylparabcn / Ethylparaben / propylparaben Butyl paraben - SEPPIC) 0.30%

SEPICIDE® CI (imidazolidinyl urea - SEPPIC) 0.20% perfume 0.40% Colorant 0.03%

Claims

1. Cosmetic use as a soothing agent, of an N-acylated compound of an amino acid of general formula:

R— CO— NH— CH— COOH (I) I

R 'in which:

R-CO represents a linear or branched alkyl radical having 12 carbon atoms, preferably a lauroyl radical; R 'represents the characterizing chain of said amino acid; a salt of this compound or a mixture of such compounds, or their salts.

2. Use according to claim 1, characterized in that the aforementioned compound of formula (I) is an N-acylated derivative of glutamic acid.

3. Use according to claim 1 of a mixture of compounds of formula (I), characterized in that said mixture consists of the product of the acylation reaction with lauric acid where one of its acylating derivatives, d '' a mixture of pure amino acids or from the complete hydrolysis of proteins.

4. Use according to claim 3, characterized in that the aforementioned acylating derivative is the chloride of lauric acid.

5. Use according to claim 3 or 4, characterized in that the aforementioned amino acid mixture is a mixture of glutamic acid, glycine, alanine and aspartic acid. preferably substantially equal amounts in weight.

6. Use according to claim 3 or 4, characterized in that the aforementioned mixture of amino acids is a mixture of alanine and glycine.

7. Use according to any one of claims 1 to 6, characterized in that the (or the) compound (s) of formula (I) above (s) is (or are) in association with dipotassium glycyrrhizinate.

8. Use according to any one of claims 1 to 7, characterized in that the (or the) compound (s) of formula (I) above (s) is (or are) in association with at least one mineral element chosen preferably from potassium and magnesium.

9. Composition, in particular cosmetic, with soothing activity, characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— CO— NH— CH— COOH (I) I

R 'in which:

R-CO represents a linear or branched alkyl radical having 12 carbon atoms, preferably a lauroyl radical; R 'represents the characterizing chain of said amino acid; a salt of this compound or a mixture of such compounds; or their salts, in combination with an effective amount of dipotassium glycyrrhizinate or alpha bisabolol.

10. Composition according to claim 9, characterized in that the effective amount of compound (s) of formula (I) above is between 0.1 and

5% expressed as weight, relative to the total weight of the composition.

11. Composition according to claim 9 or 10, characterized in that the weight ratio between lc (s) compound (s) of formula (I) and the dipotassium glycyrrhizinate or alpha bisabolol is between 4: 1 and 1: 4 .

12. Composition, in particular cosmetic, with soothing activity, characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— CO— NH— CH— COOH (1)

I R 'in which:

R 'represents the characterizing chain of said amino acid; a salt of this compound or a mixture of such compounds; or their salts, in combination with an effective amount of at least one mineral element, preferably chosen from potassium and magnesium.

13. Composition according to claim 9, characterized in that the effective amount of compound (s) of formula (I) above is between 0.1 and 5% expressed by weight, relative to the total weight of the composition.

14. Composition according to claim 12 or 13, characterized in that the weight ratio between the compound (s) of formula (I) and the mineral element is between 1:50 and 1:35.

15. Cosmetic composition characterized in that it contains an effective amount of an N-acylated compound of an amino acid of general formula:

R— O— NH— CH— COOH (I)

R 'in which:

R-CO represents a linear or branched alkyl radical having 12 carbon atoms, preferably a lauroyl radical; R 'represents the characterizing chain of said amino acid; a salt of such a compound, or a mixture of such compounds, or their salts, combined with a cosmetic active ingredient capable of inducing neurosensitive reactions on the skin.

16. Composition according to Claim 15, characterized in that the cosmetic active principle capable of inducing the aforementioned neuro-sensitive reactions is vitamin A acid or an alpha-hydroxy acid.

17. Composition according to claim 15 or 16, characterized in that the weight ratio between lc (s) compound (s) of formula (1) and the cosmetic active principle capable of inducing neurosensitive reactions is between 99 / 1 and 10/90.