Novel use of anacardic acid and the salts of same for an antifungal application with a cosmetic purpose

Abstract

The invention relates to the use of anacardic acid and the salts of same for an antifungal application with a cosmetic purpose as an anti-dandruff agent.

Description

[0001] NEW USE OF ANACARDIC ACID AND ITS SALTS FOR ANTIFUNGAL APPLICATION FOR COSMETIC PURPOSES

[0002] The invention relates to a new use of anacardic acid and its salts for an antifungal application for cosmetic purposes. The invention relates to a cosmetic composition having an antifungal action. The invention relates to a dermatological composition having an antifungal action.

[0003] CONTEXT OF THE INVENTION

[0004] Dandruff is small fragments (scales) of the scalp made up of dead cells that fall off, spreading through the hair or falling onto the shoulders.

[0005] A microscopic fungus called Malassezia furfur or pityrosporum ovale is known to be involved in excessive scalp flaking and the appearance of dandruff. This fungus is a lipophilic yeast, belonging to the Fungi imperfect! group and part of the natural commensal flora of humans (present in practically 100% of the population on all skin types and its presence is completely normal).

[0006] Dandruff is a hair problem that affects almost one in two people, mainly younger men. While not serious, it can have an impact on self-esteem and quality of life. Generally, a cosmetic treatment based on an anti-dandruff shampoo can help to combat it, as well as specific treatments (lotions).

[0007] These shampoos generally contain: an antifungal (which acts on the fungus); a keratolytic (an exfoliant); soothing agents to combat itching.

[0008] Normally, the scalp renews itself approximately every 21 days. However, in some cases, cell renewal cycles last only 5 to 7 days. These accelerated cycles are a consequence of seborrheic dermatitis. The precise cause of seborrheic dermatitis has not yet been fully understood, but it is believed to be linked to the proliferation of Malassezia furfur.

[0009] Cashew Nut Shell Liquid (CNSL) is a natural oil derived from cashew nut shells. The main components of raw (natural) CNSL are phenolic compounds: anacardic acid, cardol, and cardanol. Methyl cardol is also present, but in trace amounts (<5%).

[0010] Each of these compounds is itself a mixture of products, comprising an alkyl or alkenyl chain, said alkenyl chain having 1, 2 or 3 double bonds (Diagram 1): anacardic acid cardol methyl cardol cardanol

[0011] 65% 15 to 20% trace 10%

[0012] Scheme 1 - Chemical structures of the main constituents of natural CNSL.

[0013] One of the aims of the invention is to provide a new active ingredient applicable to the scalp. Another aim of the invention is to provide a new natural or naturally occurring compound, derived from plant and natural sources, as a cosmetic active substance. 0 Another aim of the invention is the recovery of CNSL compounds, derived from agricultural production waste, in the cosmetic field.

[0014] Another object of the invention is to provide a cosmetic composition for improving the condition of the scalp of a healthy individual.

[0015] Another aim of the invention is to provide a dermatological composition making it possible to prevent or treat a state of scalp dysfunction.

[0016] Use

[0017] An object of the present invention relates to the cosmetic use of at least one acid of formula (I) and / or one of its salts of formula (II), in which:

[0018] R represents a linear alkyl chain of 15 carbon atoms, saturated or unsaturated, which may comprise one to several double bonds, in particular 1 to 3 double bonds,

[0019] (Cation+) represents the associated cation of the salt of formula (II) and is of organic or mineral origin, as an anti-dandruff agent by topical application to prevent or limit the formation of dandruff on the healthy scalp of a healthy human subject.

[0020] The inventors unexpectedly found that the acid of formula (I) and its acid salts of formula (II) exhibit an antifungal action on the fungal strain Malassezia furfur, making it possible to be used as an anti-dandruff agent. These compounds exhibited an inhibitory activity on the growth of the fungal strain Malassezia furfur, demonstrated by the tests of examples 9 to 11. The term "anti-dandruff agent" means an active ingredient in the form of a compound or composition, capable of eliminating and / or limiting the presence or formation of dandruff, in particular on the scalp.

[0021] According to a particular embodiment, the invention relates to the use as defined above of at least one compound of formula (I).

[0022] According to a particular embodiment, the invention relates to the use as defined above of at least one compound of formula (II).

[0023] According to a particular embodiment, the invention relates to the use as defined above of at least one compound of formula (I) and at least one compound of formula (II).

[0024] According to a particular embodiment, the invention relates to the use as defined above, in which R comprises from 0 to 3 double bonds, in particular 0, 1, 2 or 3 double bonds.

[0025] Advantageously, in the case of a combination of at least two compounds, the number of double bonds of the R group of each of said compounds is independent of each other. According to a particular embodiment, the invention relates to the use as defined above, in which the cation (Cation+) is of organic origin.

[0026] According to a particular embodiment, the invention relates to the use as defined above, in which the cation (Cation+) is of mineral origin.

[0027] Advantageously, in the case of a combination of at least two compounds of formula (II), the cation (Cation+) of each of said compounds is independent of each other.

[0028] According to a particular embodiment, the invention relates to the use as defined above, in which said anti-dandruff agent also has keratolytic properties.

[0029] Furthermore, compounds of formula (I) and its salts of formula (II) such as anacardic acids are also known to exhibit a keratolytic effect.

[0030] Thus, the compounds of formula (I) and its salts of formula (II) have the advantage of being anti-dandruff agents both through their antifungal action on Malassezia furfur and through their keratolytic action.

[0031] A "keratolytic action" means a biological action that allows the keratin layer of the skin to be detached and eliminated.

[0032] According to a particular embodiment, the invention relates to the use as defined above, in which said anti-dandruff agent acts by an antifungal and keratolytic action.

[0033] According to a particular embodiment, the invention relates to the use as defined above, in which said anti-dandruff agent acts by an antifungal and exfoliating action.

[0034] By "an exfoliating action" we mean a cosmetic action allowing detachment in strips or sheets.

[0035] Another subject of the present invention relates to the cosmetic use of at least one acid of formula (I) and / or one of its salts of formula (II) as an exfoliating agent by topical application to prevent or limit the formation of dandruff on the healthy scalp of a healthy subject.

[0036] The inventors have found that the acid of formula (I) and its acid salts of formula (II) have an exfoliating action, in particular by keratolytic action, making it possible to maintain the morphology of the skin after application, while promoting the desquamation process of the stratum corneum (examples 12 to 14). In particular, the skin explants tolerated contact with anacardic acid well for almost a week. The term "exfoliating agent" means an active ingredient in the form of a compound or composition, capable of reducing the number of layers of corneocytes in the stratum corneum.

[0037] Another subject of the present invention relates to the cosmetic use of at least one acid of formula (I) and / or one of its salts of formula (II) as an anti-dandruff agent and as an exfoliating agent by topical application to prevent or limit the formation of dandruff on the healthy scalp of a healthy subject.

[0038] According to a particular embodiment, the invention relates to the use as defined above, in which said salt is such that the cation (Cation+) associated with the anion derived from the acid is:

[0039] - mineral and chosen from alkali metals, in particular a sodium cation (Na + ) or a potassium cation (K + ), Or

[0040] - organic and is a cationic form of a primary, secondary or tertiary amine.

[0041] According to a particular embodiment, the invention relates to the use as defined above, in which the cation (Cation+) associated with the anion derived from the acid is mineral and chosen from alkali metals.

[0042] Advantageously the cation (Cation+) is the sodium cation (Na + ) or the potassium cation (K + ).

[0043] According to a particular embodiment, the invention relates to the use as defined above, in which the cation (Cation+) associated with the anion derived from the acid is organic and is the cationic form of a primary or secondary or tertiary amine.

[0044] According to a particular embodiment, the invention relates to the use as defined above, in which said cation (Cation+) is an organic cation and is the cationic form of an organic amine or an amino acid.

[0045] According to a particular embodiment, the invention relates to the use as defined above, in which said cation (Cation+) is an organic cation and is the cationic form of an organic amine.

[0046] According to a particular embodiment, the invention relates to the use as defined above, in which said cation (Cation+) is an organic cation and is the cationic form of an amino acid.

[0047] According to a particular embodiment, the invention relates to the use as defined above, in which said organic cation (Cation+) is chosen from the cationic form of lysine, arginine and histidine. Advantageously, said organic cation is lysine.

[0048] According to a particular embodiment, the invention relates to the use as defined above, in which said salt is such that the cation associated with the anion derived from the acid is:

[0049] - mineral and chosen from alkali metals, in particular a sodium cation (Na + ) or a potassium cation (K + ), Or

[0050] - organic and is the cationic form of a primary or secondary or tertiary amine, in particular wherein said cation is an organic cation and is the cationic form of an organic amine or an amino acid, preferably wherein said organic cation is selected from the cationic form of lysine, arginine or histidine.

[0051] According to a particular embodiment, the invention relates to the use as defined above, in which each R group of said acid(s) of formula (I) and / or one of its salts of formula (II), is independently of one another: a saturated linear alkyl chain of 15 carbon atoms, or a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, or a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, or a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds.

[0052] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent is an acid of formula (I) in which the group R is: a saturated linear alkyl chain of 15 carbon atoms, or a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, or a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, or a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds. According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent is an acid of formula (I) chosen from acids A, B, C and D of the following formulas:

[0053] D (C15:3)

[0054] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent consists of a mixture of 4 acids (AAO, AA1, AA2, AA3) of formula (I), in which: the R group of the AAO acid is a saturated linear chain of 15 carbon atoms, the R group of the AA1 acid is a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, the R group of the AA2 acid is a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, and the R group of the AA3 acid is a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds.

[0055] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent consists of a mixture of 4 acids A, B, C and D of the following formulas:

[0056]

[0057] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent is a salt of an acid, of formula (II), in which the group R is: a saturated linear alkyl chain of 15 carbon atoms, or a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, or a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, or a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds.

[0058] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent is a salt of an acid, of formula (II), of associated cation (Cation+), said salt being chosen from the compounds of the following formulas:

[0059] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent consists of a mixture of 4 salts of the acids (SAO, SA1, SA2, SA3) of formula (II), in which: the R group of the SAO acid is a saturated linear chain of 15 carbon atoms, the R group of the SA1 acid is a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, - the R group of the SA2 acid is a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, and the R group of the SA3 acid is a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds. According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent consists of a mixture of four acid salts of the following formulae:

[0060] According to a particular embodiment, the invention relates to the use as defined above, in which said salts are lysine salts.

[0061] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent is a lysine salt chosen from the following formulas:

[0062]

[0063] (I ysinc SA3)

[0064] According to a particular embodiment, the invention relates to the use as defined above, in which the anti-dandruff agent consists of a mixture of four lysine acid salts of the following formulae:

[0065]

[0066] (1 ysmo SA3)

[0067] According to a particular embodiment, the invention relates to the use as defined above, in which the group R is a linear alkyl chain of 15 saturated carbon atoms.

[0068] According to a particular embodiment, the invention relates to the use as defined above, in which each group R of said acid(s) of formula (I) and / or one of its salts of formula (II), is independently of one another: - a saturated linear alkyl chain of 15 carbon atoms, or a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, or a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, or a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds, in particular in which said salts of formula (II) are lysine salts, preferably in which the group R is a saturated linear alkyl chain of 15 carbon atoms.

[0069] According to a particular embodiment, the invention relates to the use as defined above, in which the acid of formula (I) is of formula (AA) and / or one of its salts is of formula (LA) following:

[0070] According to a particular embodiment, the invention relates to the use as defined above, in which the acid of formula (I) is of the following formula (AA):

[0071] According to a particular embodiment, the invention relates to the use as defined above, in which one of its salts of formula (II) is of the following formula (LA):

[0072] According to a particular embodiment, the invention relates to the use as defined above, in which said at least one acid and / or one of its salts is derived or prepared from cashew nut shell oil (CNSL).

[0073] Advantageously, said at least one acid and / or one of its salts are of natural origin.

[0074] According to a particular embodiment, the invention relates to the use as defined above, in which the total concentration of said at least one acid and / or one of its salts is from 0.025 to 2.500% m / v, preferably from 0.050 to 1.000% m / v.

[0075] “% m / v” means a concentration of active ingredient expressed according to the following equation: 100

[0076] With rrisoiuté in grams and V so iution in mL.

[0077] For example, a 1% w / v solution is equivalent to 1 g of solute in 100 mL of solution, or a mass concentration C m of 10 g / L or 10 mg / mL.

[0078] The range of "0.025 to 2.500% w / v" includes the following ranges of values: from 0.025 to 0.030% w / v; from 0.030 to 0.035% w / v; from 0.035 to 0.040% w / v; from 0.040 to 0.045% w / v; from 0.045 to 0.050% w / v; from 0.050 to 0.100% w / v; from 0.100 to 0.200% w / v; from 0.200 to 0.300% w / v; from 0.300 to 0.400% w / v; from 0.400 to 0.500% w / v; from 0.500 to 0.600% w / v; from 0.600 to 0.700% w / v; from 0.700 to 0.800% w / v; from 0.800 to 0.900% w / v; from 0.900 to 1.000% w / v; from 1.000 to 1.100% w / v; from 1.100 to 1.200% w / v; from 1.200 to 1.300% w / v; from 1.300 to 1.400% w / v; from 1.400 to 1.500% w / v; from 1.500 to 1.600% w / v; from 1.600 to 1.700% w / v; from 1.700 to 1.800% w / v; from 1,800 to 1,900% w / v; from 1,900 to 2,000% w / v; from 2,000 to 2,100% w / v; from 2,100 to 2,200% w / v; from 2,200 to 2,300% w / v; from 2,300 to 2,400% w / v; from 2,400 to 2,500% w / v.The range of "0.050 to 1.000% w / v" includes the following ranges of values: 0.050 to 0.055% w / v; 0.055 to 0.060% w / v; 0.060 to 0.065% w / v; 0.065 to 0.070.

[0079] % w / v; from 0.070 to 0.075% w / v; from 0.075 to 0.080% w / v; from 0.080 to 0.085% w / v; from 0.085 to 0.090% w / v; from 0.090 to 0.095% w / v; from 0.095 to 0.100% w / v; from 0.100 to 0.125% w / v; from 0.125 to 0.150% w / v; from 0.150 to 0.175% w / v; from 0.175 to 0.200

[0080] % w / v; from 0.200 to 0.225% w / v; from 0.225 to 0.250% w / v; from 0.250 to 0.275% w / v; from 0.275 to 0.300% w / v; from 0.300 to 0.325% w / v; from 0.325 to 0.350% w / v; from 0.350 to 0.375% w / v; from 0.375 to 0.400% w / v; from 0.400 to 0.425% w / v; from 0.425 to 0.450% w / v; from 0.450 to 0.475% w / v; from 0.475 to 0.500% w / v; from 0.500 to 0.525% w / v; from 0.525 to 0.550% w / v; from 0.550 to 0.575% w / v; from 0.575 to 0.600% w / v; from 0.600 to 0.625% w / v; from 0.625 to 0.650% w / v; from 0.650 to 0.675% w / v; from 0.675 to 0.700% w / v; from 0.700 to 0.725% w / v; from 0.725 to 0.750% w / v; from 0.750 to 0.775% w / v; from 0.775 to 0.800% w / v; from 0.800 to 0.825% w / v; from 0.825 to 0.850% w / v; from 0.850 to 0.875% w / v; from 0.875 to 0.900% w / v; from 0.900 to 0.925% w / v; from 0.925 to 0.950% w / v; from 0.950 to 0.975% w / v; from 0.975 to 1.000% w / v.

[0081] According to a particular embodiment, the invention relates to the use as defined above, in which said at least one acid and / or one of its salts is formulated in an anti-dandruff composition, in particular in the form of a lotion or a shampoo or a conditioner or a cream or a hair mask.

[0082] According to a particular embodiment, the invention relates to the use as defined above, wherein said at least one acid and / or one of its salts is derived or prepared from cashew nut shell oil (CNSL), and / or wherein the total concentration of said at least one acid and / or one of its salts is from 0.025 to 2.500% w / v, preferably from 0.050 to 1.000% w / v, and / or wherein said at least one acid and / or one of its salts is formulated in an anti-dandruff composition, in particular in the form of a lotion or a shampoo or a conditioner or a cream or a hair mask.

[0083] Another subject of the invention relates to an anti-dandruff composition comprising as active ingredient, in a physiologically acceptable medium for topical application to healthy scalp, said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to the invention above, as sole anti-dandruff agent, said anti-dandruff agent having an antifungal action, said active ingredient being present at a concentration of 0.025 to 2.500% w / v, preferably of 0.050 to 1.000% w / v.

[0084] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, comprising as active ingredient, in a physiologically acceptable medium for topical application to healthy scalp, said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to the invention above, as an anti-dandruff agent, in particular as the sole anti-dandruff agent, said anti-dandruff agent having an antifungal action, said active ingredient being present at a concentration of 0.025 to 2.500% w / v, preferably of 0.050 to 1.000% w / v.

[0085] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in which the anti-dandruff agent has an antifungal action and also has keratolytic properties.

[0086] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in which said composition is free from other anti-dandruff agents.

[0087] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, comprising as active ingredient, in a physiologically acceptable medium for topical application to healthy scalp, said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to the invention above, as sole anti-dandruff agent, said anti-dandruff agent having an antifungal action, said active ingredient being present at a concentration of 0.025 to 2.500% w / v, preferably of 0.050 to 1.000% w / v.

[0088] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in which said single anti-dandruff agent has an antifungal action and also has keratolytic properties.

[0089] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in the form of a lotion or a shampoo or a conditioner or a mask or a hair cream.

[0090] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in which the anti-dandruff agent has an antifungal action and also has keratolytic properties, and / or is in the form of a lotion or a shampoo or a conditioner or a mask or a hair cream.

[0091] According to a particular embodiment, the invention relates to an anti-dandruff composition as defined above, in which said single anti-dandruff agent has an antifungal action and also has keratolytic properties, and / or is in the form of a lotion or a shampoo or a conditioner or a mask or a hair cream.

[0092] According to a particular embodiment, the invention relates to an anti-dandruff shampoo as defined above, comprising:

[0093] - 0.025 to 2.500% w / v, preferably 0.050 to 1.000% w / v of active ingredient having antifungal action, in particular against Malassezia furfur.

[0094] Another subject of the present invention relates to an anti-dandruff composition comprising as active ingredient said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to the invention above, as anti-dandruff agent and exfoliating agent in a physiologically acceptable medium for topical application to healthy scalp, 0.025 to 2.500% w / v, preferably 0.050 to 1.000% w / v of active ingredient allowing an antifungal action and a keratolytic or exfoliating action without denaturing the dermis and the epidermis at least one soothing agent chosen from: allantoin and its derivatives, glycyrrhetinic acid, stearyl glycyrrhetinate, azulene, gaiazulene, beta-carotene, hafnia biolysate, bisabolol and panthenol.

[0095] A soothing agent is an active substance with a soothing effect on the skin that helps prevent and / or combat non-pathological skin manifestations of inflammatory origin.

[0096] Another subject of the present invention relates to a non-therapeutic cosmetic process for preventing and / or limiting the formation of dandruff on the scalp, comprising at least one step of topical application to a healthy scalp (of a healthy human subject) of a composition comprising at least one acid of formula (I) and / or one of its salts of formula (II) as defined above, optionally followed by a rinsing step.

[0097] Another subject of the invention relates to a composition comprising at least one acid of formula (I) and / or at least one of its salts of formula (II): in which:

[0098] R represents a linear alkyl chain of 15 carbon atoms, saturated or unsaturated, which may comprise one to several double bonds, in particular 1 to 3 double bonds,

[0099] (Cation+) represents the associated cation of the salt of formula (II) and is of organic or mineral origin, for its use in preventing and / or treating localized and / or systemic infections caused by the fungal strain Malassezia furfur. Figures and examples

[0100] Figure 1 represents microscopy images of the general morphology of a skin explant after staining with Masson's trichrome illustrating the appearance of the stratum corneum: part A is an image obtained on a control explant on D1 illustrating a thin and compact stratum corneum and part B is an image obtained on an explant on which an exfoliating product was applied on D1 illustrating a thick and clearly laminated stratum corneum.

[0101] Figure 2 represents microscopy images illustrating the general morphology of the dermis, epidermis and stratum corneum of a skin explant after staining with Masson's trichrome: the images (TJO) of the first row correspond to those of a control explant at D0, the images (TJ6) of the second row correspond to those of a control explant at D6, the images (EJ6) of the third row correspond to those of an explant treated with ethanol at D6, the images (PJ6) of the fourth row correspond to those of an explant treated with the product to be tested at D6.

[0102] Figure 3 represents the histogram of the mean values, with the associated standard deviations, of the epidermal thickness measurements of the explants at D6 for the control batch at D6 (TD6), the batch treated with ethanol at D6 (ED6) and the batch treated with the product at D6 (PD6).

[0103] Figure 4 represents microscopy images after the Mackenzie test to determine the number of layers of corneocytes in the stratum corneum of a skin explant: the images (TJO) of the first row correspond to those of a control explant at D0, the images (TJ6) of the second row correspond to those of a control explant at D6, the images (EJ6) of the third row correspond to those of an explant treated with ethanol at D6, the images (PJ6) of the fourth row correspond to those of an explant treated with the product to be tested at D6.

[0104] Figure 5 represents the histogram of the number of corneocyte layers and the standard deviation of the explant measurements at D6 for the control batch at D6 (TD6), the batch treated with ethanol at D6 (ED6) and the batch treated with the product at D6 (PD6).

[0105] Example 1: Synthesis of anacardic acid contained in natural CNSL

[0106] Extraction step of natural CNSL from cashew nut shells

[0107] Natural CNSL was obtained from cashew nut shells by a solvent extraction process. The required mass of previously ground cashew nut shells was suspended in the desired solvent (ethyl acetate, mass concentration of: m CO ques / Vsoivant = 1 / 2.5) at 50°C for 3 h. The suspension was then filtered, the shells were washed with solvent, and then the filtrates were combined. Natural CNSL was obtained after removal of the solvent.

[0108] Thus, 160 kg of previously crushed cashew shells were introduced into a filter bottom tank equipped with a felt filter cloth (apparent porosity of approximately 25 μm). 360 kg of ethyl acetate (400 L) were then added to the tank. The suspension was then stirred at 50°C for 3 h. Vacuum filtration was then carried out to separate the filtrate from the extracted shell residues. 216 kg of ethyl acetate (240 L) were then introduced into the filter bottom tank and the suspension was again stirred at 50°C for 30 minutes. A second vacuum filtration was carried out to separate the filtrate from the extracted shell residues. The two filtrates are then combined, and the solvent is removed under reduced pressure using a falling film concentrator, at an evaporation temperature between 25 and 50°C.56.6 kg of natural CNSL are thus obtained (black oil, the mass percentage of ethyl acetate is 13.4%, yield r = 31% excluding ethyl acetate).

[0109] NMR- 1 H (400 MHz, CDCh): 7.35 (t, J = 7.9 Hz, H acide anaca rd iq u e ), 7.13 (t, J = 7.6 Hz, H cardano i), 6.88 - 6.86 (m, H aC anacardial ide), 6.78 - 6.74 (m, H aC anacardic ide and Hcardanol), 6.66 - 6.63 (m, Hcardanol), 6.24 (m, Hcardol and Hmethyl cardol), 6.18 (S, Hcardol), 5.87 5.76 (m, Hc=c), 5.46 5.30 (m, Hc=c), 5.07 — 4.96 (m, Hc=c), 2.99 — 2.96 (m, H a anacardic cide), 2.82 — 2.76 (m, Hside chain), 2.57 2.53 (m, Hcardanol), 2.50 2.43 (m, Hcardol and Hmethyl cardol), 2.10 (S, Hmethyl cardol), 2.11 2.00 (m,

[0110] Hside chain), 1.63 1.53 (m, Hside chain), 1.40 1.25 (m, Hside chain), 0.93 0.86 (m, Hside chain).

[0111] Precipitation step of anacardic acid contained in natural CNSL

[0112] Anacardic acid was isolated from CNSL by a precipitation method in the presence of a base and a divalent cation. The process consisted of solubilizing natural CNSL in a 95 / 5 V / V ethanol / water mixture, then precipitating the anacardic acid contained in the oil by adding calcium hydroxide (> 35% by mass). The suspension was left stirring at 50°C for 3 hours. It was then filtered to recover the anacardate salt. The latter was then acidified with a concentrated HCl solution to reprotonate the anacardic acid, then the product of interest was isolated from the aqueous phase by L / L extraction. The latter is in the form of a mixture of 4 major species: - A: 6-pentadecylsalicylic acid

[0113] - B: 6-[8(Z) — pentadecenyl] salicylic acid

[0114] - C: 6-[8(Z), 11(Z) — pentadecadienyl] salicylic acid

[0115] - D: 6-[8(Z), 11(Z), 14 — pentadecatilenyl] salicylic acid

[0116] A quantity of 4.65 kg of natural CNSL comprising a residual mass percentage of ethyl acetate of 13.2%, was dissolved in 14 L of ethanol (96%) and 700 mL of tap water, in a 25 L reactor by stirring at 50°C. 1.6 kg of calcium hydroxide (96% purity), corresponding to 38% by mass relative to the CNSL, were then added to the medium. The suspension was left stirring at 90 rpm at 50°C for 3 h, then it was transferred to a 30 L Nutsche filter. After filtration, the solid was rinsed with 2 X 4 L of ethanol, then it was suspended in 4 L of tap water and 8 L of ethyl acetate. 12 L of a 6 M hydrochloric acid solution were then added to the suspension. The latter was stirred until the solid was completely dissolved. The medium was left to stand for decantation, then the aqueous phase was extracted with 8 L of ethyl acetate.The two organic phases were then combined and transferred to a 50 L decanter. The final organic phase was washed with 2 x 12 L of saturated NaCl solution, then the solvent was removed under reduced pressure (rotary evaporator) at 50°C. The final product thus obtained is a brown paste (3.10 kg, yield r = 72% relative to the mass of CNSL, purity p = 94%).

[0117] NMR- 1 H (400 MHz, CDCI3): 7.36 (1 H, t, J = 8 Hz), 6.87 (1 H, dd, Ji = 8.4 and J2= 1.2 Hz), 6.77 (1 H, dd, Ji = 7.4 and J2= 1.2 Hz), 5.86 - 5.76 (m, H c =c), 5.47 - 5.30 (m, H c =c), 5.074 - 4.96 (m, Hc=c), 2.99 — 2.95 (2H, m), 2.84 — 2.76 (m, H side chain), 2.07 — 1.99 (m, H side chain), 1.63 — 1.56 (m, H side chain), 1.40 1.25 (m, H side chain), 0.92 0.86 (m, H side chain).

[0118] Example 2: Synthesis of hydrogenated anacardic acid

[0119] Hydrogenation step

[0120] Hydrogenated anacardic acid A (C15:0) can be obtained by catalytic hydrogenation of the mixture of the four anacardic acid molecules (A, B, C and D) obtained in the precipitation step described in Example 1. This hydrogenation was carried out in a polar protic solvent, in the presence of a source of dihydrogen and a catalyst (such as a palladium catalyst supported on a carbon support (Pd / C) for example). The suspension was left stirring at room temperature under a dihydrogen atmosphere until the double bonds of the side chains of the anacardic acid molecules B, C and D disappeared (kinetic monitoring by NMR). The suspension was then filtered and the hydrogenated anacardic acid (A) was recovered after removal of the solvent from the filtrate.

[0121] Recrystallization step

[0122] Hydrogenated anacardic acid (A) is recrystallized from an alkane solvent (such as cyclohexane) to obtain a creamy-white solid after drying.

[0123] Preparation by hydrogenation followed by recrystallization

[0124] 55.44 g of anacardic acid (1,61,10' 1mol, 1 eq.) were dissolved in 250 mL of ethanol (96%) by stirring at room temperature. 2.01 g of a 5% Pd / C catalyst (i.e. 3.6% by mass relative to the anacardic acid) were then added to the medium. The latter was bubbled under argon for 10 minutes, then under dihydrogen for 15 minutes. The suspension was then left stirring and under a dihydrogen atmosphere at room temperature for 22h15. The suspension was then filtered using a millipore filter, then the solvent was removed under reduced pressure (rotary evaporator) at 50°C. 53.99 g of hydrogenated anacardic acid was obtained (beige solid, yield r = 96.3%).

[0125] NMR- 1 H (400 MHz, CDCI3): 7.36 (1 H, m), 6.88 (1 H, dd, Ji = 8.4 and J2= 1.2 Hz), 6.78 (1 H, dd, Ji = 7.5 and J2= 1.2 Hz), 3.01 - 2.96 (2H, m), 1.66 - 1.56 (2H, m), 1.40 - 1.25 (24H, m), 0.91 - 0.86 (3H, m).

[0126] 40.1 g of hydrogenated anacardic acid were dissolved in 200 mL of cyclohexane at 80°C for 30 minutes. Once the medium was homogeneous, it was left to stand at room temperature for 1 hour, then it was immersed in a cold water bath (water + ice cubes) for 1 hour 30 minutes. A brown solid then formed in the medium. This solid was recovered by filtration on a porosity 4 frit, then it was washed on the frit with 60, then 2x70 mL of cold cyclohexane (previously stored at 5°C). The solid was then dried under reduced pressure (rotary evaporator) at 50°C, then it was dried using a vane pump at room temperature for 5 hours 15 minutes. 27.069 g of a creamy white solid were thus obtained (yield r = 67.5%, purity p > 97% by HPLC).

[0127] Lot AR130623-192: RMN- 1 H (400 MHz, acetone-d6): 7.35 - 7.31 (1H, t, J = 7.8 Hz), 6.79 - 6.77 (2H, m), 2.99 -

[0128] 2.95 (2H, m), 1.60 (2H, m), 1.35 - 1.28 (24H, m), 0.89 - 0.86 (3H, m).

[0129] NMR- 13 C (101 MHz, acetone-d6): 173.71, 163.65, 147.27, 134.86, 123.01, 116.08, 113.33, 36.86, 33.05, 32.70, 30.60 - 29.77, 23.39, 14.42.

[0130] SM (ESI -): m / z = 347.3 (MH)'.

[0131] Lot JL-070524-303:

[0132] NMR- 1 H (400 MHz, acetone-d6): 7.36 - 7.32 (1 H, m, J = 7.9 Hz), 6.80 - 6.77 (2H, m), 2.99 -

[0133] 2.96 (2H, m), 1.64 - 1.57 (2H, m), 1.37 - 1.28 (24H, m), 0.89 - 0.86 (3H, m).

[0134] Example 3: Preparation of anacardic acid salts

[0135] The salts are obtained by adding one equivalent of the salifying compound to anacardic acid, either to the mixture of the four anacardic acid molecules A, B, C and D, or to hydrogenated anacardic acid.

[0136] Se / s from anacardic acid and triethylamine! E / E') or from anacardic acid and lysine (F / F')

[0137] The salt of formula E (anacardic acids-triethylamine) is obtained by adding one equivalent of triethylamine, dissolved in ethanol, to an ethanolic solution of a mixture of anacardic acids A, B, C and D. The salt is obtained after removal of the solvent by lyophilization.

[0138] The salt of formula E' (hydrogenated anacardic acid-triethylamine) is obtained by adding one equivalent of triethylamine, dissolved in ethanol, to an ethanolic solution of hydrogenated anacardic acid. The salt is obtained after removal of the solvent by lyophilization. Se / s from anacardic acid and lysine

[0139] The salt of formula F (anacardic acids-lysine) is obtained by adding one equivalent of lysine, solubilized in water, to an ethanolic solution of a mixture of anacardic acids A, B, C and D. The salt is obtained after removal of the solvent by lyophilization.

[0140] The salt of formula F' (hydrogenated anacardic acid-lysine) is obtained by adding one equivalent of lysine, dissolved in water, to an ethanolic solution of hydrogenated anacardic acid. The salt is obtained after removal of the solvent by lyophilization.

[0141] Example 4: Preparation of hydrogenated anacardic acid-triethylamine salt (E')

[0142] 1.00 g of hydrogenated anacardic acid (2,841.10' 3 mol, 1 eq.) were dissolved in 5 mL of absolute ethanol by stirring at room temperature. In parallel, 290 mg of triethylamine (99%, 2.841.10' 3mol, 1 eq.) were dissolved in 3 mL of absolute ethanol by stirring at room temperature. The triethylamine solution was then added dropwise into the ethanolic anacardic acid solution with 2 mL of absolute ethanol as a rinse. The medium was left stirring at room temperature for 15 minutes, then the solvents were removed by lyophilization for 6 h, then under vacuum using a vane pump for 4 h. 1.29 g of a pale pink solid were thus obtained (yield r = 99%).

[0143] NMR- 1 H (400 MHz, CD3OD / D2O 90 / 10): 7.08 (1 H, t, J = 7.8 Hz), 6.65 - 6.59 (2H, m), 3.18 - 3.12 (6H, m), 3.06 - 3.03 (2H, m), 1.59 - 1.52 (2H, m), 1 .30 - 1.27 (33H, m), 0.88 (3H, t, J = 6.7 Hz).

[0144] NMR- 13 C (101 MHz, CD3OD / D2O 90 / 10): 176.0, 161.8, 147.1, 131.7, 122.4, 120.2, 114.9, 47.7, 36.2, 33.4, 33.0 31.0 - 30.7, 30.4, 23.7, 14.5, 9.2.

[0145] MS (ESI -): m / z anionic part (anacardate) = 347.3 (MH)-; (ESI +): m / z cationic part (triethylamine) = 102.1 (M+H) + .

[0146] Example 5: Preparation of non-hydrogenated anacardic acid-triethylamine salt (E)

[0147] 1,009 g of anacardic acid (2,753.10' 3 mol, 1 eq.) were dissolved in 10 mL of absolute ethanol by stirring at room temperature. In parallel, 279 mg of triethylamine (99%, 2,730.10' 3mol, 0.99 eq.) were dissolved in 3 mL of absolute ethanol by stirring at room temperature. The triethylamine solution was then added dropwise into the ethanolic anacardic acid solution with 2 mL of absolute ethanol as a rinse. The medium was left stirring at room temperature for 15 minutes, then the solvents were removed by lyophilization for 6 h, then under vacuum using a vane pump for 4 h. 1.217 g of a brown pasty solid were thus obtained (yield r = 95%).

[0148] NMR- 1 H (400 MHz, CD3OD / D2O 90 / 10): 7.10 (1 H, t, J = 7.8 Hz), 6.66 - 6.61 (2H, m), 5.85 - 5.75 (m), 5.44 - 5.29 (m), 5.05 - 4.94 (m), 3.18 - 3.12 (6H, m), 3.05 - 3.01 (2H, m), 2.82 - 2.74 (2H, m), 2.06 - 1.97 (m), 1.59 - 1.51 (2H, m), 1.36 - 1.26 (m), 0.92 - 0.86 (3H, m).

[0149] NMR- 13C (101 MHz, CD3OD / D2O 90 / 10): 175.9, 161.7, 147.1, 137.9, 131.8, 131.2, 131.0, 130.9, 130.8, 130.7, 130.2, 129.2, 129.0, 128.6, 127.7, 122.4, 120.0, 115.1, 114.9, 36.2, 33.2,

[0150] 32.8, 32.4, 30.8 - 30.2, 29.9, 28.1 , 28.0, 26.5, 26.4, 23.8, 23.6, 14.5, 14.1 , 9.2.

[0151] MS (ESI -): m / z anionic part (anacardate) = 341.2 (triene form), 343.2 (diene form), 345.2 (monoene form), 347.3 (saturated form) (MH)-; (ESI +): m / z cationic part (triethylamine) = 102.1 (M+H) + .

[0152] Example 6: Preparation of hydrogenated anacardic acid salt with lysine (F')

[0153] 6.092 g of hydrogenated anacardic acid (1,748.10' 2 mol, 1 eq.) were solubilized in 60 mL of absolute ethanol by stirring at room temperature. In parallel, 2.612 g of L-lysine (98%, 1,751.10' 2mol, 1 eq.) were dissolved in 20 mL of distilled water by stirring at room temperature. The lysine solution was then added dropwise into the ethanolic anacardic acid solution with 10 mL of rinsing water. The medium was left stirring at room temperature for 15 minutes, then the solvents were removed under reduced pressure (rotary evaporator) at 50°C. The solid was dried by lyophilization for 16 h, then under vacuum using a vane pump for 7 h. 8.349 g of a pale pink solid were thus obtained (yield r = 95.9%).

[0154] NMR- 1 H (400 MHz, CD3OD / D2O 90 / 10): 7.09 (1 H, t, J = 7.8 Hz), 6.66 - 6.60 (2H, m), 3.61 (1 H, t, J = 6.1 Hz), 3.05 - 3.01 (2H, m), 2.98 - 2.94 (2H, m), 1 .91 - 1.85 (2H, m), 1.71 (2H, quintuplet, J = 7.6 Hz), 1.58 - 1.45 (4H, m), 1.30 - 1.25 (24H, m), 0.88 (3H, t, J = 6.7 Hz).

[0155] NMR- 13C (101 MHz, CD3OD / D2O 90 / 10): 176.1, 174.9, 161.4, 147.0, 131.6, 122.4, 120.4,

[0156] 114.8, 55.7, 40.3, 36.0, 33.1, 32.9, 31.5, 30.8 - 30.2, 28.0, 23.6, 22.9, 14.4.

[0157] MS (ESI -): m / z anionic part (anacardate) = 347.3 (MH)-; (ESI +): m / z cationic part (lysine) = 147.1 (M+H) + , 130.1 (M+H-NH3) + .

[0158] Example 7: Preparation of non-hydrogenated anacardic acid salt with lysine (F)

[0159] 1.00 g of anacardic acid (2,728.10' 3 mol, 1 eq.) were solubilized in 10 mL of absolute ethanol by stirring at room temperature. In parallel, 407 mg of L-lysine (98%, 2,728.10' 3mol, 1 eq.) were dissolved in 3 mL of distilled water by stirring at room temperature. The lysine solution was then added dropwise into the ethanolic anacardic acid solution with 2 mL of rinsing water. The medium was left stirring at room temperature for 15 minutes, then the solvents were removed by lyophilization for 6 h, then under vacuum using a vane pump for 4 h. 1.014 g of a brown pasty solid were thus obtained (yield r = 72%).

[0160] NMR- 1 H (400 MHz, CD3OD / D2O 90 / 10): 7.08 (1 H, t, J = 7.8 Hz), 6.66 - 6.60 (2H, m), 5.85 - 5.75 (m), 5.44 - 5.29 (m), 5.04 - 4.94 (m), 3.61 (1 H, t, J = 6.1 Hz), 3.05 - 3.01 (2H, m), 2.97

[0161] - 2.93 (2H, m), 2.81 - 2.74 (m), 2.06 - 1.98 (m), 1.92 - 1.85 (2H, m), 1.71 (2H, quintuple, J = 7.6 Hz), 1.59 - 1.45 (4H, m), 1.36 - 1.26 (m), 0.91 - 0.86 (3H, m).

[0162] NMR- 13C (101 MHz, CD3OD / D2O 90 / 10): 176.2, 174.7, 161.4, 146.9, 137.9, 131.6, 131.2, 130.97, 130.9, 130.8, 130.7, 130.2, 129.2, 129.0, 128.6, 127.7, 122.4, 120.5, 115.2, 114.9, 55.7, 40.3, 36.1, 33.1, 32.8, 32.4, 31.5, 30.9 - 30.2, 29.9, 28.1 - 28.0, 26.5, 26.4, 23.8, 23.6, 23.0, 14.5, 14.2.

[0163] MS (ESI -): m / z anionic part (anacardate) = 341.2 (triene form), 343.2 (diene form), 345.2 (monoene form), 347.3 (saturated form) (MH)-; (ESI +): m / z cationic part (lysine) = 147.1 (M+H) + , 130.1 (M+H-NH3) + .

[0164] Example 8: Determination of CMI inhibitory activity

[0165] The purpose of this study is to evaluate the inhibitory activity of a test compound against the strain Malassezia furfur using a microplate method. a) Principle of the test:

[0166] In a 96-well microplate, we put in contact:

[0167] - 100 pL of the compound to be tested at twice the concentration of the concentration to be tested

[0168] - with 100 pL of a double strength nutrient broth titrating approximately between 2 and 6.10 5 cfu / mL (colony forming unit).

[0169] After incubation of the microplate for a defined period of time, the optical density at 620 nm of each well containing the test compound at a defined concentration is measured. The results are expressed as a percentage of growth calculated relative to a growth control according to the following equation:

[0170] Growth percentage

[0171] _ (DO compound at concentration C — DO control absorbance of the compound at concentration C DO growth control Tl

[0172] By definition, the first lowest concentration of test compound allowing a growth percentage of less than or equal to 20% to be obtained is considered the inhibitory concentration. b) Experimental conditions

[0173] The microbial strain tested is Malassezia furfur CBS 1878.

[0174] The strain comes from the Centraal Bureau voor Schimmelcultures (CBS).

[0175] It is maintained in the laboratory according to the requirements of standard NF EN 12353.

[0176] The composition of the nutritious broth is double-strength Sabouraud Broth with added olive oil.

[0177] The incubation temperature of the microplate is 30°C + / - 1°C aerobically.

[0178] The incubation time of the microplate is 24 to 48 hours in aerobic conditions.

[0179] The compounds tested in this study are hydrogenated anacardic acid lot AR130623-192 and hydrogenated anacardic acid salt with lysine (F').

[0180] The preparation of dilutions of the compounds to be tested is carried out from stock solutions. The stock solutions are prepared at 2% by diluting (Ethanol 96° / Sterile water - 90 / 10% v / v). Successive dilutions in 1% agar are carried out.

[0181] The chosen range of concentrations of the compound to be tested (by weight of the compound per volume) is: 0.01% w / v; 0.05% w / v; 0.10% w / v; 0.50% w / v and 1.0% w / v

[0182] The typical distribution of a 96-well microplate for assessing the inhibitory concentration of a test compound against Malassezia Furfur is illustrated in the following diagram:

[0183]

[0184] Test 1 ballast 2

[0185] Thus the absorbance control wells include:

[0186] 100 pL of sterile double-strength nutrient broth and 100 pL of the test compound at double strength

[0187] The wells for testing each include:

[0188] 100 pL of nutrient broth inoculated with Malassezia Furfur at double concentration and 100 pL of the test compound at double concentration

[0189] A growth control microplate is made separately by seeding the 96 wells with:

[0190] 100 pL of nutrient broth inoculated with Malassezia Furfur at double concentration and 100 pL of a 1% agar solution. c) Expression of results

[0191] For each concentration of compound to be tested and for each test, the average of the DO values ​​measured on the 3 wells is taken and the growth percentages are calculated.

[0192] These values ​​are plotted on a graph (growth percentage versus concentration) in order to study the activity profiles of each compound to be tested.

[0193] Example 9: Inhibition tests with hydrogenated anacardic acid

[0194] Tables 1 and 2 below report respectively, for tests 1 and 2 carried out in the same microplate, the results of optical densities DO with hydrogenated anacardic acid as the compound to be tested according to the method of example 8 in which the percentage of growth is calculated from a growth control of DO measured at 0.599.

[0195] Table 1: Results of optical densities OD with hydrogenated anacardic acid as test compound and percentage growth calculated for a series of tests 1 on a microplate 1.

[0196] Table 2: Results of optical densities OD with hydrogenated anacardic acid as test compound and percentage growth calculated for a series of tests 2 on a microplate 2. Example 10: Inhibition tests with the lysine salt of hydrogenated anacardic acid

[0197] Tables 3 and 4 below report respectively, for tests 1 and 2 carried out in the same microplate, the results of optical densities DO with the lysine salt of hydrogenated anacardic acid as the compound to be tested according to the method of example 8 in which the percentage of growth is calculated from a growth control of DO measured at 0.599.

[0198] Table 3: Results of optical densities OD with the lysine salt of hydrogenated anacardic acid as test compound and percentage growth calculated for a series of tests 1 on a microplate 1.

[0199]

[0200] Table 4: Results of optical densities OD with the lysine salt of hydrogenated anacardic acid as the test compound and percentage growth calculated for a series of 2 tests on a microplate 2.

[0201] Example 11: Inhibitory activity

[0202] The summary of the results of examples 9 and 10 is presented in table 5 which reports the inhibitory concentrations (in % w / v) obtained against Malassezia furfur for hydrogenated anacardic acid and a hydrogenated anacardic acid salt (lysine salt).

[0203] Table 5: Inhibitory concentrations (in % w / v) obtained against Malassezia furfur for hydrogenated anacardic acid and a hydrogenated anacardic acid salt (lysine salt). Example 12: Ex vivo evaluation of the exfoliation activity of hydrogenated anacardic acid on explants of living human skin.

[0204] The objective of the study is to evaluate the exfoliating activity of a product from ex vivo living human skin explants.

[0205] The ex vivo phase allows the topical application of the tested products to be reproduced. The histological phase allows the modulation of biological parameters to be assessed by staining and immunolabeling.

[0206] This activity was evaluated by:

[0207] - an assessment of general morphology with a measurement of the thickness of the epidermis;

[0208] - a count of the stratum corneum layers by the McKenzie test.

[0209] Materials and methods

[0210] 1. Study plan

[0211] The study is carried out over 7 days:

[0212] JO = Day 0: Preparation of skin explants and application of the product to be tested.

[0213] D1 = Day 1: Application of the product on the skin explants

[0214] D4 = Day 4: Application of the product on the skin explants

[0215] D5 = Day 5: Application of the product on the skin explants

[0216] D6 = Day 6: Analysis of skin explants

[0217] 2. Products tested

[0218] The products tested are hydrogenated anacardic acid (lot JL-070524-303), reference OPI-AA-H, presented in the form of a white powder in a bottle, and absolute ethanol, used as an excipient (noted E in the rest of the text).

[0219] Hydrogenated anacardic acid was stored at 4°C in the dark before use and during the testing period of this study. The product to be applied is prepared at 1% in absolute ethanol, i.e. 1% (m / v), by dissolving 1 gram of product in 100 mL of absolute ethanol. The solution thus obtained is noted P in the rest of the text.

[0220] 3. Preparation of skin explants

[0221] Twelve skin explants with an average diameter of 11 mm (±1 mm) were prepared from a mammoplasty of a 49-year-old woman (reference: P3021-MB49) of phototype II according to the Fitzpatrick classification.

[0222] Explants were kept alive in 2mL of BEM (BIO-EC's Explants Medium) culture medium at 37°C in a humid atmosphere of 5% CO2.

[0223] The study is carried out on skin tissues obtained from surgical residues (cosmetic surgery) from a donor in full compliance with the Declaration of Helsinki and Article L.1243-4 of the French Public Health Code. The latter does not require prior authorization by an ethics committee for the collection and use of surgical waste.

[0224] 4. Distribution of explants for the study

[0225] The skin explants were divided into analysis batches according to the following Table 6:

[0226] Table 6

[0227] 5. Application of the product

[0228] On day 0 (D0), D1, D4 and D5, the tested products (absolute ethanol and solution P) were applied topically to batches E and P of the skin explants at a rate of 2 pL per 1 cm 2 of explant (» 2 mg / cm 2 ) and spread using a small spatula.

[0229] Before each application, the surface of the explants was gently wiped to remove excess product (from the previous application) and to mimic mechanical friction. The control explants of batch T received no treatment except gentle wiping and renewal of the culture medium.

[0230] The BEM culture medium was renewed in half (1 mL per well) on D1 and D4. According to the provisions mentioned in the study plan, the days of treatment, irradiation and sampling were adjusted to the workday schedule.

[0231] 6. Sampling

[0232] At JO, 3 explants from batches T0 were collected and cut in half. Half was fixed in buffered formalin, and the other half was frozen at -80°C.

[0233] At D6, 3 explants from each batch were taken and treated in the same way as for T0.

[0234] 7. Histological treatment

[0235] After fixation for 24 hours in buffered formalin solution, the samples were dehydrated and impregnated with paraffin using a Leica PEARL dehydrator. The samples were embedded using a Leica EG 1160 embedding station. 5 μm thick sections were cut using a Leica RM 2125 Minot microtome, and the sections were mounted on Superfrost® histological glass slides. The frozen samples were cut into 7 μm thick sections using a Leica CM 3050 cryostat. The sections were then mounted on more salinized Superfrost® glass slides. Microscopic observations were performed using a Leica DMLB microscope, an Olympus BX43 or BX63 microscope. Images were digitized with an Olympus DP digital camera equipped with cellSens storage software (Olympus).

[0236] 7.1. General morphology

[0237] General morphology was assessed by microscopic observation of formalin-fixed, paraffin-embedded (FFPE) skin sections after staining with Masson's trichrome, Goldner variant. Staining was assessed by microscopic observation.

[0238] Batches concerned: all, i.e. 12 explants. 7.2. Epidermal thickness

[0239] Epidermal thickness was measured on Masson trichrome staining images using the cellSens software measurement module.

[0240] Batches concerned: all, i.e. 12 explants, 27 measurements per batch.

[0241] 7.3. Mackenzie Test

[0242] The number of cell layers in the stratum corneum (SC) was determined by microscopic observation of cryosections processed according to the Mackenzie protocol. After swelling the corneocytes using Mackenzie solution (sodium hydroxide solution), images were taken and the number of cell layers in the SC was assessed using cell software. A D. Batches concerned: all, i.e. 12 explants.

[0243] Example 13: Morphology of the stratum corneum

[0244] The morphology of the stratum corneum (the horny layer) is characterized by two main aspects: lamination and thickness.

[0245] Lamination is assessed based on the empty spaces between corneocytes, also called basket patterns.

[0246] • In a well-hydrated stratum corneum, serine protease activity is optimal, leading to the destruction of corneodesmosomes. Corneocytes remain bound only by a few corneodesmosomes, which have been preserved by tight junctions (Igawa et al. Experimental Dermatology 2010; Kitajima et al. Dermatologica Sinica 2015), leaving empty spaces characteristic of the laminated appearance. This appearance is associated with well-hydrated skin.

[0247] • In a poorly hydrated stratum corneum, the activity of serine proteases is reduced, leading to a compact stratum corneum. This appearance is associated with dry skin.

[0248] The thickness of the stratum corneum is related to two processes: an increase in the number of corneocyte layers and / or certain morphological changes.

[0249] • An increase in terminal differentiation of keratinocytes leads to a greater quantity of corneocyte layers and therefore to a thicker horny layer.

[0250] An increase in lamination makes the stratum corneum thicker. The thickness of the stratum corneum is assessed by microscopic examination but can be measured using image analysis software. In addition, the number of corneocyte layers can be counted using the McKenzie method.

[0251] An example of the appearance of the stratum corneum after Masson trichrome staining is illustrated in Figure 1: thin and compact stratum corneum (A) for a control explant on D1 and thick and clearly laminated stratum corneum (B) for an explant treated with an exfoliating product on D1.

[0252] Example 14: Results and discussion of the study

[0253] 1. General morphology

[0254] The general morphology of the papillary dermis, the epidermis, the dermis-epidermis junction and the stratum corneum of the explants of the control batches TO at JO (noted TJO) and T at D6 (noted TJ6), of the batch treated with ethanol at D6 (noted EJ6) and of the batch treated with the test product at D6 (noted PJ6) is illustrated by the microscopy images after Masson trichrome staining in Figure 2.

[0255] The assessment of the general morphology of the different batches is indicated in table 7 below.

[0256] Table 7

[0257] Abbreviations: Nb layers = number of cell layers, Morpho = morphology, DEJ = dermis-epidermis junction, Density = density of the collagen network.

[0258] Rating of intensity values: F = Low, M = Moderate, AC = Fairly Light, C = Light, TC = Very Light

[0259] Legend for Morphology: B = Good, AB = Fairly Good, TLA = Very Slightly Altered, LA = Slightly Altered, MA = Moderately Altered, ACA = Fairly Clearly Altered, CA = Clearly Altered, TCA = Very Clearly Altered On day 0, on the control batch T0,

[0260] The stratum corneum is thin and moderately laminated.

[0261] The epidermis has 3 to 4 cellular layers with good morphology.

[0262] The relief of the dermo-epidermal junction is quite clear.

[0263] The density of the collagen network in the dermis is quite clear.

[0264] The morphology of the dermal cells is good.

[0265] On day 6, on the control batch TJ6,

[0266] The stratum corneum is distinctly thick and quite clearly laminated.

[0267] The epidermis has 4 to 5 cellular layers with a fairly good morphology.

[0268] The relief of the dermo-epidermal junction is quite clear.

[0269] The density of the collagen network in the dermis is moderate.

[0270] The morphology of the dermal cells is good.

[0271] The effect of P and E products on general morphology, compared to batch TJ6, is as follows:

[0272] => Excipient E (ethanol) induces a slight decrease in the thickness and lamination of the stratum corneum.

[0273] => Product P induces a slight decrease in the thickness of the stratum corneum.

[0274] The effect of product P on general morphology, compared to batch EJ6, is as follows:

[0275] => Product P induces a slight increase in the lamination of the stratum corneum.

[0276] 2. Thickness of the epidermis

[0277] Epidermal thickness measurements across all batches are shown in Table 8 below.

[0278]

[0279] Table 8: Values ​​of the thickness measurements (in iim) of the epidermis of the explants corresponding respectively to the control batch at D0 (TO or TJO), to the control batch at D6 (TD6), to the batch treated with ethanol at D6 (ED6) and to the batch treated with the product at D6 (PD6).

[0280] Table 9 and Figure 3 report the mean values ​​and associated standard deviations of the epidermis thickness measurements of the explants from the different batches.

[0281] Table 9: Mean values ​​of epidermal thickness and associated standard deviations

[0282] On day 0, on the control batch T0, the average thickness of the epidermis is 27.9 pm. On day 6, on the control batch TJ6, the average thickness of the epidermis is 44.9 pm.

[0283] The effect of P and E products on epidermal thickness, compared to batch TJ6, is as follows:

[0284] => Excipient E induces a non-significant decrease of 2% => Product P induces a significant decrease of 12%.

[0285] The effect of product P on epidermal thickness, compared to batch EJ6, is as follows: => Product P induces a significant decrease of 10%. 3. Counting corneocyte layers

[0286] The number of corneocyte layers in the stratum corneum of skin explants from control batches T0 to D0 (denoted TJO) and T to D6 (denoted TJ6), from the batch treated with ethanol on D6 (denoted EJ6) and from the batch treated with the test product on D6 (denoted PJ6) was determined from microscopy images of cryosections of explants treated with the Mackenzie test. These images are shown in Figure 4.

[0287] The number of corneocyte layers in the stratum corneum (SC) across the different batches is shown in Table 10 below Table 10: Values ​​of the measurements of the number of layers of corneocytes of the explants corresponding respectively to the control batch at D0 (T0 or TJO), to the control batch at D6 (TD6), to the batch treated with ethanol at D6 (ED6) and to the batch treated with the product at D6 (PD6).

[0288] Table 11 and Figure 5 report the mean values ​​and associated standard deviations of the corneocyte layer number measurements from the different batches.

[0289] Table 11: Mean values ​​of the number of corneocyte layers and associated standard deviations.

[0290] On day 0, in the control batch, the stratum corneum has 14 layers of corneocytes.

[0291] On day 6, on the control batch TJ6, the stratum corneum presents 14 layers of corneocytes.

[0292] The effect of P and E products on the number of corneocyte layers, compared to batch TJ6, is as follows:

[0293] => Excipient E induces a non-significant increase of 3%

[0294] => Product P induces a significant decrease of 14%.

[0295] The effect of product P on the number of corneocyte layers, compared to batch EJ6, is as follows:

[0296] => Product P induces a significant decrease of 16%.

[0297] 4. Conclusions

[0298] The main findings are summarized in the following Table 12.

[0299] Table 12

[0300] All products are well tolerated by human skin explants at day 6.

[0301] The Orpia OPI-AA-H (A) 1% (P) product shows good exfoliating activity. In fact, it induces:

[0302] - A slight increase in stratum corneum lamination compared to excipient E, suggesting a better desquamation process,

[0303] - A slight decrease in epidermal thickness compared to the control batch T;

[0304] - A significant decrease in the number of corneocyte layers.

Claims

CLAIMS 1. Cosmetic use of at least one acid of formula (I) and / or one of its salts of formula (II), (I) (H) in which: R represents a linear alkyl chain of 15 carbon atoms, saturated or unsaturated, which may comprise one to several double bonds, in particular 1 to 3 double bonds, (Cation+) represents the associated cation of the salt of formula (II) and is of organic or mineral origin, as an anti-dandruff agent by topical application to prevent or limit the formation of dandruff on the healthy scalp of a healthy human subject.

2. Use according to claim 1, wherein said anti-dandruff agent acts by an antifungal and keratolytic action.

3. Use according to claim 1, of at least one acid of formula (I) and / or one of its salts of formula (II) as an anti-dandruff agent and exfoliating agent by topical application to prevent or limit the formation of dandruff on the healthy scalp of a healthy subject.

4. Use according to one of claims 1 to 3, in which said salt is such that the cation associated with the anion derived from the acid is: - mineral and chosen from alkali metals, in particular a sodium cation (Na + ) or a potassium cation (K + ), Or - organic and is a cationic form of a primary, secondary or tertiary amine, in particular wherein said cation is an organic cation and is the cationic form of an organic amine or an amino acid, preferably wherein said organic cation is selected from the cationic form of lysine, arginine or histidine.

5. Use according to one of claims 1 to 4, in which each R group of said acid(s) of formula (I) and / or one of its salts of formula (II), is independently of one another: a saturated linear alkyl chain of 15 carbon atoms, or a mono-unsaturated linear alkyl chain of 15 carbon atoms comprising a double bond, or a di-unsaturated linear alkyl chain of 15 carbon atoms comprising two double bonds, or a tri-unsaturated linear alkyl chain of 15 carbon atoms comprising three double bonds, in particular in which said salts of formula (II) are lysine salts, preferably in which the R group is a saturated linear alkyl chain of 15 carbon atoms.

6. Use according to one of claims 1 to 5, in which the acid of formula (I) is of formula (AA) and / or one of its salts is of formula (LA) following:

7. Use according to one of claims 1 to 6, in which said at least one acid and / or one of its salts is derived or prepared from cashew nut shell oil (CNSL), and / or wherein the total concentration of said at least one acid and / or one of its salts is from 0.025 to 2.500% w / v, preferably from 0.050 to 1.000% w / v, and / or wherein said at least one acid and / or one of its salts is formulated in an anti-dandruff composition, in particular in the form of a lotion or a shampoo or a conditioner or a cream or a hair mask.

8. Anti-dandruff composition comprising as active ingredient, in a physiologically acceptable medium for topical application to healthy scalp, said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to one of claims 1 to 6, as anti-dandruff agent, in particular as sole anti-dandruff agent, said anti-dandruff agent having an antifungal action, said active ingredient being present at a concentration of 0.025 to 2.500% w / v, preferably of 0.050 to 1.000% w / v.

9. An anti-dandruff composition according to claim 8, wherein the anti-dandruff agent exhibits antifungal action and also has keratolytic properties, and / or is in the form of a lotion or shampoo or conditioner or hair mask or cream.

10. Anti-dandruff composition comprising: as active ingredient said at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to one of claims 1 to 5, as anti-dandruff agent and exfoliating agent in a physiologically acceptable medium for topical application to healthy scalp, at a rate of 0.025 to 2.500% w / v, preferably 0.050 to 1.000% w / v of active ingredient allowing an antifungal action and a keratolytic or exfoliating action without denaturing the dermis and the epidermis, at least one soothing agent chosen from: allantoin and its derivatives, glycyrrhetinic acid, stearyl glycyrrhetinate, azulene, gaiazulene, beta-carotene, hafnia biolysate, bisabolol and panthenol.

11. Non-therapeutic cosmetic process for preventing and / or limiting the formation of dandruff on the scalp, comprising at least one step of topical application to a healthy scalp (of a healthy human subject) of a composition comprising at least one acid of formula (I) and / or one of its salts of formula (II) as defined according to one of claims 1 to 6, optionally followed by a rinsing step.

12. Composition comprising at least one acid of formula (I) and / or at least one of its salts of formula (II): (I) (II) in which: R represents a linear alkyl chain of 15 carbon atoms, saturated or unsaturated, which may comprise one to several double bonds, in particular 1 to 3 double bonds, (Cation+) represents the associated cation of the salt of formula (II) and is of organic or mineral origin, for its use in preventing and / or treating localized and / or systemic infections caused by the fungal strain Malassezia furfur.

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