Use of at least one Thiopyridinone compound or compositions containing it to improve the skin barrier function

Abstract

Use of at least one thiopyridinone compound or compositions comprising it to improve the skin barrier function. The present invention relates to the use of at least one thiopyridinone compound or compositions comprising it to improve the skin barrier function. It also relates to a cosmetic treatment method comprising applying said thiopyridinone compound(s) or compositions comprising them to the skin to improve the skin barrier function.

Description

Title of the invention: Use of at least one Thiopy-ridinone compound or compositions comprising it to improve the barrier function of the skin

[0001] The present invention relates to the field of active ingredients capable of improving the barrier function of the skin, for a cosmetic application and in particular the use of at least one compound of formula (I) or (!), as described below, and / or their optical isomers, geometric isomers as well as their acid or base salts, organic or mineral, and / or their solvates such as hydrates, or at least one composition comprising it or them, to improve the barrier function of the skin

[0002] The skin is the body's first barrier to the external environment. Human skin is made up of several compartments, namely a superficial compartment, the epidermis, the dermis, and a deep compartment, the hypodermis.

[0003] The human epidermis is composed mainly of three types of cells: keratinocytes, which are the vast majority, melanocytes and Langerhans cells. Each of these cell types contributes through its own functions to the essential role played in the body by the skin, in particular the role of protecting the body from external aggressions, which is called the "barrier function".

[0004] The epidermis is conventionally divided into a basal layer of keratinocytes constituting the germinative layer of the epidermis, a so-called spinous layer consisting of several layers of polyhedral cells arranged on the germinative layers, one to three so-called granular layers and finally the horny layer (or stratum corneum), consisting of a set of layers of keratinocytes at the terminal stage of their differentiation called comeocytes. Comeocytes are anucleated cells mainly composed of a fibrous matrix containing cytokeratins, surrounded by a very resistant structure 15 nm thick, called the horny envelope. The stacking of these comeocytes constitutes the horny layer which is responsible for the barrier function of the epidermis.

[0005] The stratum corneum constitutes a real protective barrier against exogenous factors and endogenous water loss. Its good renewal as well as the quality of its structure are essential to ensure an effective barrier against the outside world and limit water loss causing dehydration, dry skin (Velarde MC. J. Invest. Dermatol., 2017, 137, 1206). The increase in epidermal differentiation and epidermal renewal lead in particular to a thickening of the epidermis, which tends to thin with age, and helps to strengthen the barrier function of the skin. This renewal also contributes to the improvement of the surface condition of the skin, and the prevention and / or treatment of roughness or alteration of the skin's micro-relief. The renewal of the epidermis thus leads to the reduction of fine lines on the skin's surface and has a beneficial effect on repair in the event of aggressions such as scratches.

[0006] Furthermore, the cohesion of the epidermis as a water barrier is ensured thanks to the tight junctions between keratinocytes. Strengthening the quality of the epidermis by favoring intracellular junctions and the cohesion of the horny layer contributes to maintaining the functions of the epidermis, as well as good hydration.

[0007] There therefore remains a need to strengthen the quality of the epidermis by prioritizing epidermal renewal, which is a basic element allowing the functions of the epidermis to be maintained, and in particular good hydration.

[0008] Certain thiopyridinone compounds have already been proposed in the prior art, in particular in documents WO2012 / 080075 and WO2017 / 102349, as active agents for the skin, for the purposes of depigmentation and / or whitening thereof, and therefore for an effect quite distinct from that considered according to the invention.

[0009] Surprisingly, the inventors have in fact demonstrated the particular properties of at least one compound of formula (I) and / or (I') below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures or of at least one composition comprising it or them to modify the expression of the HBEGF and KRT19 genes on a model of normal human keratinocytes in monolayer.

[0010] All of these properties therefore advantageously make it possible to envisage the use of at least one compound of formula (I) and / or (I') below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of a composition comprising it or them to renew the epidermis and improve the barrier function of the skin. Summary of the invention

[0011] Thus, the present invention relates to the cosmetic use for improving the barrier function of the skin of at least one compound of formula (I) and / or (I') below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition comprising it or them:

[0012] Formulas (I) and (!') in which:

[0013] - A represents a divalent hydrocarbon chain, saturated or unsaturated, of preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, interrupted by one or more (thio)amide(s) -C(X)-N(R')- or (NR')-C(X)- groups, and optionally substituted, in particular by one or more identical or different groups chosen from the group consisting of i) -OR and ii) -S-R3;

[0014] - M denotes a radical chosen from the group consisting of a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 alkyl group, c) an alkali metal, d) an alkaline earth metal, or e) an ammonium group; preferably M represents a) a hydrogen atom or d) an alkali metal;

[0015] - Ri denotes a radical chosen from the group consisting of: a. a hydrogen atom, b. a linear C1-C10 or branched C3-C10 saturated alkyl group optionally substituted by one or more groups, identical or different, chosen from the group consisting of i) -O-R3 and ii) -S-R3; preferably, Ri represents a hydrogen atom;

[0016] - R3 denotes a radical chosen from a) a hydrogen atom, b) an alkyl group saturated linear C1-C10 or branched C3-C10; preferably, R3 represents a hydrogen atom;

[0017] - X represents an oxygen atom, a sulfur atom, preferably an atom of oxygen;

[0018] - R' represents a hydrogen atom or a C1-C4 alkyl group, in particular Ci preferably represents a hydrogen atom.

[0019] The use according to the invention thus makes it possible to achieve the objectives as described above, by using at least one thiopyridinone compound of formula (I), as defined above, and / or at least one tautomer of a thiopyridinone compound of formula (I) (i.e. a compound of formula (!) as defined above), and / or one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or a composition comprising said compound(s) of formula (I) or (!') as defined above.

[0020] The use according to the invention makes it possible to improve the barrier function of the skin, in particular by increasing epidermal differentiation and epidermal renewal leading to a thickening of the epidermis.

[0021] The use according to the invention also makes it possible to improve the surface condition of the skin, and to prevent and / or treat roughness or alteration of the micro-relief of the skin. The use according to the invention makes it possible to reduce the number and / or size of fine lines on the surface of the skin and has a beneficial effect on skin repair in the event of aggressions such as scratches.

[0022] The use according to the invention also makes it possible to maintain the functions of the epidermis, and more particularly good hydration, as well as the prevention and / or treatment of cosmetic signs associated with sensitive or dry skin.

[0023] The present invention also relates to a cosmetic treatment method for improving the barrier function of the skin comprising a step of applying to the skin a cosmetic composition comprising at least one compound of formula (I) and / or (!') below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0024] The present invention also relates to a cosmetic treatment method for improving the surface condition of the skin, preventing and / or treating roughness or alteration of the micro-relief of the skin, and / or reducing the number and / or size of fine lines on the surface of the skin, comprising a step of applying to the skin a cosmetic composition comprising at least one compound of formula (I) and / or (!) below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0025] The present invention also relates to a cosmetic treatment process for preventing and / or treating the cosmetic signs associated with sensitive or dry skin comprising a step of applying to the skin a cosmetic composition comprising at least one compound of formula (I) and / or (!') below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0026] The compound(s) of formula (I) or (!') is or are thiopyridinone compounds leading to an improvement in the barrier function of the skin.

[0027] The compound(s) of formula (I) or (!) lead(s) in particular to an improvement in the surface condition of the skin, to the prevention and / or treatment of roughness or alteration of the micro-relief of the skin, and / or to the reduction of the number and / or size fine lines on the surface of the skin.

[0028] The compound(s) of formula (I) or (!) lead(s) in particular to better prevention and / or treatment of cosmetic signs associated with sensitive or dry skin.

[0029] Other objects, characteristics, aspects and advantages of the invention will appear even more clearly on reading the description and the example which follows. Definitions

[0030] The term “physiologically acceptable medium” means a medium compatible with the skin, that is to say when it does not generate tingling, pulling or unacceptable discomfort for the user.

[0031] By "the skin" is meant the entire skin of the body, and the scalp and preferably, the skin of the face, the décolleté, the neck, the arms and forearms, the hands or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, lips, chin), the décolleté and the neck.

[0032] According to the invention, by "prevent" or "prevention" is meant the fact of reducing the risk of occurrence or slowing down the occurrence of a given phenomenon, namely, reducing the risk of appearance of cosmetic signs associated with sensitive or dry skin.

[0033] By "treat" or "treatment" we mean any action aimed at improving the comfort and well-being of an individual; this term therefore covers alleviating, relieving and curing.

[0034] By “intended to be administered topically” is meant an application to the surface of the skin in question.

[0035] In what follows, and unless otherwise indicated, the limits of a domain of values ​​are included in this domain, in particular in the expressions “between” and “ranging from ... to ...”.

[0036] Furthermore, the expression "at least" used in the present description is equivalent to the expression "greater than or equal to".

[0037] Finally, in a manner known per se, the term “Cn” or “Cn” compound or group denotes a compound or group containing “n” carbon atoms in its chemical structure.

[0038] Throughout the description, including the claims, the expression "comprising a" should be understood as being synonymous with "comprising at least one", unless otherwise specified. Detailed description of the invention

[0039] Compounds of formula (I) and (!')

[0040] Preferably, the thiopyridinone compound(s) for use according to the invention is(are) chosen from the group consisting of the compounds of formula (I) or (!'), as well as one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures:

[0041] Formulas (I) and (!') in which:

[0042] - A represents a divalent hydrocarbon chain, saturated or unsaturated, of preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, interrupted by one or more (thio)amide(s) -C(X)-N(R')- or (NR')-C(X)- groups, and optionally substituted, in particular by one or more identical or different groups chosen from the group consisting of i) -O-R3 and ii) -S-R3;

[0043] - M denotes a radical chosen from the group consisting of a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 alkyl group, c) an alkali metal, d) an alkaline earth metal, or e) an ammonium group; preferably M represents a) a hydrogen atom or d) an alkali metal;

[0044] - Ri denotes a radical chosen from the group consisting of:

[0045] a) a hydrogen atom,

[0046] b) a linear C1-C10 or branched C3-C10 saturated alkyl group optionally substituted by one or more groups, identical or different, chosen from the group consisting of i) -O-R3 and ii) -S-R3; preferably, R1 represents a hydrogen atom;

[0047] - R3 denotes a radical chosen from a) a hydrogen atom, b) an alkyl group saturated linear C1-C10 or branched C3-C10; preferably, R3 represents a hydrogen atom;

[0048] -X represents an oxygen atom, a sulfur atom, preferably an oxygen atom,

[0049] - R' represents a hydrogen atom or a C1-C4 alkyl group, in particular Ci, preferably R' represents a hydrogen atom.

[0050] In other words, the thiopyridinone compound(s) for use in the invention is(are) chosen from the group consisting of the compounds of formula (I), the tautomers of formula (I), as well as one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their isomers optical, their geometric isomers and their mixtures.

[0051] According to one embodiment, in formulas (I) and (!'), Ri represents a hydrogen atom.

[0052] According to one embodiment, in formulas (I) and (!'), M represents c) an alkali metal or d) an alkaline earth metal, preferably M represents c) an alkali metal such as sodium or potassium.

[0053] According to another embodiment, in formulas (I) and (!), M represents an ammonium group.

[0054] According to another embodiment, in formulas (I) and (!), M represents a linear C1-C10 or branched C3-C10 alkyl group.

[0055] According to this embodiment, in formulas (I) and (!'), M represents a linear saturated C1-C10, in particular C1-C6, more particularly C1-C4 alkyl group, such as methyl or ethyl, or a branched saturated C3-C10, in particular C3-C6, more particularly C3-C4 alkyl group.

[0056] According to this embodiment, in formulas (I) and (!'), M represents a saturated, preferably linear, C1-C4 alkyl group, in particular methyl.

[0057] Preferably, in formulas (I) and (!), M represents a hydrogen atom or an alkali metal.

[0058] Alternatively, preferably, in formulas (I) and (!'), M represents c) an alkali metal, d) an alkaline earth metal or e) an ammonium, preferably M represents an alkali metal such as sodium or potassium.

[0059] Preferably, M represents a hydrogen atom, a saturated C1-C4 alkyl group, such as methyl or ethyl, or an alkali metal.

[0060] Preferably, in formulas (I) and (!'), A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, comprising from 1 to 8 carbon atoms, particularly A represents a (C2-C6)alkylene group, linear or branched, preferably linear; said chain A being interrupted by a group -C(X)-N(R')- with X and R' as defined previously, more particularly -C(O)-N(H)-.

[0061] Preferably, in formulas (I) and (!), A represents a group CH2 -C(O)-N(R')-CH2- or -CH2-N(R')-C(X)-CH2- with X and R' as defined above, preferably -CH2-C(O)-N(H)-CH2-.

[0062] Preferably, the compound(s) of formula (I) and (!), their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, are such that:

[0063] - Ri denotes a radical chosen from the group consisting of:

[0064] a) a hydrogen atom,

[0065] b) a linear C1-C10 or branched C3-C10 saturated alkyl group optionally substituted by one or more groups, identical or different, chosen from the group consisting of i) -O-R3 and ii) -S-R3; preferably, Ri represents a hydrogen atom;

[0066] - A represents a (C2-C6)alkylene group, linear or branched, preferably linear; said chain A being interrupted by a group -C(X)-N(R')- with X and R' as defined previously and preferably representing -C(O)-N(H)-;

[0067] - M denotes a radical chosen from the group consisting of a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 alkyl group, in particular a C1-C4 alkyl group, c) an alkali metal, d) an alkaline earth metal, or e) an ammonium group; preferably M represents a) a hydrogen atom, b) a C1-C4 alkyl group, d) an alkali metal;

[0068] - R3 denotes a radical chosen from a) a hydrogen atom, b) an alkyl group saturated linear C1-C10 or branched C3-C10; preferably, R3 represents a hydrogen atom;

[0069] - X represents an oxygen atom, a sulfur atom, preferably an atom of oxygen;

[0070] - R' represents a hydrogen atom or a C1-C4 alkyl group, in particular Ci, preferably R' represents a hydrogen atom.

[0071] Preferably, the compound(s) of formula (I) and (I'), their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, are such that: - Ri represents a hydrogen atom, - R' represents a hydrogen atom or a C1-C4 alkyl group, in particular particular in Ci, preferably R' represents a hydrogen atom; - A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, comprising from 1 to 8 carbon atoms, particularly A represents a (C2-C6)alkylene group, linear or branched, preferably linear; said chain A being interrupted by a group -C(X)-N(R')- with X and R' as defined previously, preferably -C(O)-N(H)-; more particularly A represents a group CH2-C(O)-N(R')-CH2- or -CH2 -N(R')-C(X)-CH2- with X and R' as defined previously, preferably -CH2-C(O)-N(H)-CH2-; - M being as defined above, preferably represents a hydrogen atom, an alkali metal, or a linear or branched C1-C4 alkyl group, such as methyl or ethyl, more preferably represents a hydrogen atom or an alkali metal such as sodium or potassium.

[0072] More preferably, the compound(s) of formula (I) or (!') is or are chosen from the group consisting of the compounds of formula (IA) or (IB) below and / or one of their acid or base salts, organic or mineral, their solvates, such as hydrates, their optical isomers, their geometric isomers and their mixtures:

[0073] Formulas (IA) and (IB) in which: - Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical optionally substituted by one or more hydroxyl (OH) or thiol (SH) radicals; and - n and m independently denote an integer equal to 1 or 2 or 3: - M has the same meaning as for compounds of formula (I) or (I'); by in particular M represents a hydrogen atom, an alkali metal, or an alkyl group, linear or branched, C1-C4 alkyl such as methyl or ethyl, preferably a hydrogen atom or an alkali metal such as sodium or potassium.

[0074] According to one embodiment, in formulas (IA) and (IB), the index n is equal to 1.

[0075] According to one embodiment, in formulas (IA) and (IB), the index m is equal to 1.

[0076] According to a particular embodiment, in formulas (IA) and (IB), n is equal to m.

[0077] According to one embodiment, in formulas (IA) and (IB), n and m are different.

[0078] According to one embodiment, in formulas (IA) and (IB), Ra denotes an atom of hydrogen.

[0079] According to one embodiment, in formulas (IA) and (IB), Rb denotes a hydrogen atom.

[0080] According to a particular embodiment, in formulas (IA) and (IB), Ra and Rb are identical.

[0081] According to one embodiment, in formulas (IA) and (IB), Ra and Rb are different.

[0082] According to one embodiment, in formulas (IA) and (IB), Ra denotes a radical C1-C4 alkyl substituted by one or more hydroxy (OH) or thiol (SH) radicals, preferably substituted by a radical chosen from OH or SH.

[0083] According to one embodiment, in formulas (IA) and (IB), Ra denotes a C1-C4 alkyl radical substituted, more preferably by an OH radical.

[0084] According to one embodiment, Rb denotes a C1-C4 alkyl radical substituted by one or more hydroxyl (OH) or thiol (SH) radicals, preferably substituted by a radical chosen from OH or SH, more preferably by an OH radical.

[0085] According to one embodiment, in formulas (IA) and (IB), Rb denotes a radical unsubstituted C1-C4 alkyl such as methyl.

[0086] Preferably, in formulas (IA) and (IB): - n and m are identical and are equal to 1, - Ra and Rb, identical or different, denote a hydrogen atom or a linear or branched C1-C4 alkyl radical, optionally substituted by one or more hydroxyl (OH) or thiol (SH) radicals, preferably substituted by a radical chosen from OH or SH, more preferably substituted by an OH radical; - M represents a hydrogen atom, an alkali metal or a linear or branched CrC4 alkyl group, preferably methyl or ethyl.

[0087] According to a particularly preferred embodiment, the compounds of formula (I) or (I') or (IA) or (IB) are chosen from the compounds of formulas (la) to (li) or (la) to (i) below as well as their tautomers and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures:

[0088] with M as defined above, particularly M represents a hydrogen atom, an alkali metal, or a linear or branched C1-C4 alkyl group such as methyl or ethyl, more preferably a hydrogen atom or an alkali metal such as sodium or potassium.

[0089] According to a very particularly preferred embodiment, the compounds of formula (I) or (!') or (IA) or (IB) are chosen from the compounds of formulas (la) or (la) above and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures:

[0090] Even more preferably, the compounds of formula (I) or (I') or (IA) or (IB) are chosen from the compounds of formula (I), and more particularly from the compounds of formulas (I-1) or (I' 1) or (1-2) or (1'2), below and / or one of their acid or base salts, organic or mineral, in particular their sodium or potassium salts, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures:

[0091] According to the present invention, the compounds of formula (I' 1) and (I' 2) correspond to the tautomers of the compounds of formula (I-1) and (I-2).

[0092] Advantageously, the compound according to the invention is the compound of formula (1-2) or (1'2).

[0093] Preferably, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formula (I) or (I'), and / or one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0094] Preferably, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulae (IA) or (IB), and / or one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0095] Preferably, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulae (la) to (li) or (la) or (l'i), and / or one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0096] Preferably, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulae (la) to (li) or (la) to (li), in particular the compound of formula (la) or (la), and / or one of their tautomers, one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0097] Even more preferably, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulas 1-1,12, and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0098] Advantageously, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulas I-1, I2, I' 1 or I'2, and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0099] Even more advantageously, the thiopyridinone compound(s) for use according to the invention is or are chosen from the group consisting of the compounds of formulas 12 or 1'2, and / or one of their tautomers, one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0100] Acceptable solvates of the compounds of formula (I) or (!') include conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents.

[0101] For example, solvates due to the presence of water or linear or branched alcohols such as ethanol or isopropanol may be mentioned.

[0102] Optical isomers include enantiomers and diastereoisomers.

[0103] Geometric isomers are in particular isomers having a geometric configuration Z / Z, Z / E, E / Z and E / E. Composition

[0104] The composition according to the invention comprises at least one compound of formula (I) or (I'), as described above, and / or one of its acid or base salts, organic or mineral, one of its solvates, such as hydrates, one of its optical isomers, one of its geometric isomers, and mixtures thereof.

[0105] The compound(s) of formula (I) or (!') are as described above.

[0106] The composition according to the invention may comprise at least two distinct thiopyridinone compounds, and of formula (I) or (!') as described previously.

[0107] According to a particular embodiment, the composition according to the invention comprises at least two compounds of formula (I) or (I'), preferably two compounds of formula (I) or (I').

[0108] More preferably, the composition according to the invention comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formula (IA) or (IB), in particular chosen from compounds (la) to (li) or (la) to (li) as defined above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0109] Preferably, the composition according to the invention comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formula (la) to (li) or (la) to (li), in particular the compound of formula (la) or (la), and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0110] More preferably, the composition according to the invention comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formulas (la) to (li) or (la) to (li), in particular the compound of formula (la) or (la) and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0111] Even more preferably, the composition according to the invention comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formulas 1-1, 12, 1'1 or 1'2, and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0112] Advantageously, the composition according to the invention comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formulas 1-1, 12,1' 1,1'2, and / or one of their tautomers, one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures.

[0113] Preferably, the composition comprises at least one compound of formula (I) or (!') chosen from the group consisting of the compounds of formula (IA) or (IB), in particular chosen from the group consisting of the compounds of formulas (la) to (li) or (la) to (li), as defined above, more particularly the compound of formula (la) or (la), even more preferably from the compounds of formulas I-1,12, their tautomers, their salts, isomers and / or solvates.

[0114] The composition according to the invention, as described above, may be aqueous, preferably is aqueous.

[0115] The pH of the composition is preferably acidic, i.e. the pH value is preferably strictly less than 7.

[0116] The composition may further comprise at least one organic solvent, preferably chosen from the group consisting of C1-C4 alcohols, in particular ethanol.

[0117] In other words, the composition according to the invention may comprise water and optionally at least one organic solvent, as defined above, preferably water and at least one organic solvent as defined above.

[0118] The composition according to the invention may be in particular in the form of an aqueous, hydroalcoholic, optionally gelled solution, a dispersion of the lotion type, optionally two-phase, an oil-in-water or water-in-oil or multiple emulsion, an aqueous gel, a dispersion of oils in an aqueous phase, in particular using spherules, these spherules being able to be polymeric particles or better, lipid vesicles of ionic and / or non-ionic type, or even in the form of a powder, a serum, a paste or a flexible stick or even a stick. It may be of solid, pasty, or more or less fluid liquid consistency. It may optionally be applied to the skin in the form of an aerosol. It may also be in solid form, and for example in the form of a stick.

[0119] Thus, the composition may comprise all the constituents usually used in the topical application and administration envisaged.

[0120] A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersion of an aqueous phase in a fatty phase (W / O) or of a fatty phase in an aqueous phase (O / W), of liquid or semi-liquid consistency of the milk type, or of soft, semi-solid or solid consistency of the cream or gel type, or even of multiple emulsion (W / O / W or O / W / O). These compositions are prepared according to the usual methods.

[0121] The composition according to the invention preferably contains at least 0.001% by weight of thiopyridinone compounds of formula (I) or (!), preferably at least 0.003% by weight, relative to the total weight of the composition.

[0122] Thus, the quantity of the thiopyridinone compound(s) of formula (I) or (!') in the composition according to the invention is preferably between 0.001% and 70% by weight, more preferably between 0.003% and 60% by weight, even more preferably between 0.005% and 50% by weight, even more preferably between 0.01 and 40% by weight, relative to the total weight of the composition.

[0123] (Other optional additives)

[0124] The composition according to the present invention may also comprise any other optional additive(s) usually used in the field of cosmetics, chosen, for example, from solvents, chelating agents, cosmetic active agents other than the thiopyridinone compound of formula (I) or (!'), such as oils, preservatives, and mixtures thereof.

[0125] It is part of the ordinary operations for those skilled in the art to adjust the nature and quantity of the above optional additives which may be present in the composition according to the present invention in such a way that the desired cosmetic properties are not affected thereby.

[0126] The compositions, in particular cosmetic compositions, capable of being used in the context of the invention generally comprise a physiologically acceptable medium.

[0127] Of course, those skilled in the art will take care to choose this or these possible additional ingredients and / or active ingredients, and / or their quantity, in such a way that the advantageous properties of the thiopyridinone compound according to the invention are not, or not substantially, altered by the envisaged addition.

[0128] Use

[0129] As indicated above, the present invention relates to the use of at least one compound of formula (I) or (I'), as described above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition comprising it or them, as defined above, for improving the barrier function of the skin.

[0130] The compound(s) of formula (I) or (!') used are as defined above.

[0131] The composition used in accordance with the present invention is as defined above.

[0132] Preferably, the invention relates to the use of at least one compound chosen from the group consisting of the compounds of formula (I) or (!') as described above, preferably chosen from the compounds of formula (IA) or (IB), as described above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition comprising it or them, as defined above, to improve the barrier function of the skin.

[0133] Preferably, the invention relates to the use of at least one compound of formula (I) or (I') chosen from the compounds of formulas (IA) or (IB), in particular chosen from the group consisting of the compounds of formulas (Ia) to (Ii) or (Ia) to (Ii), in particular the compounds of formula (Ia) or (Ia), more preferably chosen from the group consisting of the compounds of formulas (I-1), (I-2), their tautomers, their salts, isomers and / or solvates, or at least one composition comprising it or them, as defined above, for improving the barrier function of the skin.

[0134] Advantageously, the use according to the invention is a use for improving the surface condition of the skin, for preventing and / or treating roughness or alteration of the micro-relief of the skin, and / or for reducing the number and / or size of fine lines on the surface of the skin.

[0135] Advantageously, the use according to the invention is a use for preventing and / or treating cosmetic signs associated with sensitive or dry skin.

[0136] Method for improving the barrier function

[0137] As indicated previously, the invention relates in particular to a method for improving the barrier function of the skin, comprising at least the application on said skin of at least one compound of formula (I) or (!), as described above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition, as defined above, comprising it or them.

[0138] The compound(s) of formula (I) or (!') used in the process according to the invention are as defined above.

[0139] The composition used in the method according to the invention is as defined above. The composition thus comprises at least one compound of formula (I) or (I'), as defined above.

[0140] Preferably, the method according to the invention comprises at least the application to the skin of at least one compound chosen from the group consisting of the compounds of formula (I) or (I'), as defined above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition comprising it or them.

[0141] The invention relates in particular to a method for improving the barrier function of the skin, comprising at least the application to said skin of at least one compound of formula (I) or (I'), as defined above, preferably chosen from the compounds of formulas (IA) or (IB), in particular chosen from the group consisting of the compounds of formulas (Ia) to (Ii) or (Ia) to (Ii), in particular the compounds of formula (Ia) or (Ia), more preferably chosen from the group consisting of the compounds of formulas (I-1), (I-2), their tautomers, their salts, isomers and / or solvates, or at least one composition comprising it or them, as defined above.

[0142] Preferably, the method according to the invention is a cosmetic method for improving the surface condition of the skin, for preventing and / or treating roughness or alteration of the micro-relief of the skin, and / or for reducing the number and / or size of fine lines on the surface of the skin.

[0143] Advantageously, the use according to the invention is a use for preventing and / or treating cosmetic signs associated with sensitive or dry skin.

[0144] Said thiopyridinone compound(s) according to the invention, or said composition containing them, are implemented, within the framework of a use or a method according to the invention, by topical route.

[0145] The compositions according to the invention may be applied directly to the skin or, alternatively, to cosmetic supports of the occlusive or non-occlusive type, intended to be applied locally to the skin. As non-limiting examples of cosmetic supports, mention may in particular be made of a patch, a wipe, a roll-on and a pen.

[0146] The composition may or may not be rinsed off after being applied to the skin, preferably not rinsed off.

[0147] A cosmetic implementation of the invention is therefore only aimed at aesthetic defects of the skin, and therefore does not exert a therapeutic effect.

[0148] The present invention relates to a non-therapeutic cosmetic skin care application of at least one thiopyridinone compound as described above or of a composition, in particular a cosmetic composition, comprising said thiopyridinone compound(s).

[0149] By “treatment” we mean a non-therapeutic treatment capable of producing an aesthetic effect without preventing or correcting a pathological dysfunction of the skin.

[0150] Skin surface

[0151] The surface of human skin is not smooth. It has a relief resulting in fine lines, distinct from wrinkles, observable under a magnifying glass in children and with the naked eye in the elderly. These fine lines or furrows intersect to form polygonal structures, namely the microrelief of the skin.

[0152] The number and depth of the furrows constituting the microrelief of the skin can be affected by numerous external or internal factors.

[0153] Advantageously, a compound of formula (I) or (!), as described above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or a composition comprising it or them, as defined above, can be used to prevent and / or treat an alteration of the surface condition of the skin, in particular following an alteration of the barrier function of the skin.

[0154] More particularly still, a compound of formula (I) or (!') as described above, and / or one of their acid or base salts, organic or inorganic, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or a composition comprising it or them, as defined above, can be used to prevent and / or treat an alteration of the microrelief of the skin, to reduce the number of furrows of the microrelief of the skin, to smooth the surface of the skin, to prevent and / or treat an irregularity of the surface of the skin, in particular to prevent and / or treat a condition of roughness of the skin, or to reduce the depth of the furrows of the microrelief of the skin.

[0155] Dry skin

[0156] One of the functions of the Stratum Corneum is to capture and retain the water contained in the epidermis, and any alteration of its structure and / or its function, in particular following or associated with an alteration of the barrier function of the skin, may result in changes in skin hydration. Hydration is provided to the skin by water from the deeper layers and by sweat. An imbalance in skin hydration can have profound consequences, both physiological and cosmetic.

[0157] Physiologically, dry skin is often associated with a decrease in the skin's hydration level as well as a change in the maturation process of the Stratum Corneum. Sensory-wise, dry skin can be characterized by a feeling of tightness and / or skin tension.

[0158] A compound of formula (I) or (I'), as described above, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or a composition comprising it or them, as defined above, may be particularly suitable for preventing and / or treating dry skin and / or cutaneous signs associated with dry skin.

[0159] Whatever the origin, skin affected by dry skin can generally present the following signs: rough and scaly appearance to the touch, as well as reduced suppleness and elasticity.

[0160] According to one embodiment, a cosmetic use of the invention may advantageously be suitable for preventing and / or treating dry or fragile skin, and winter xerosis.

[0161] According to one embodiment, a cosmetic use of the invention may advantageously be suitable for preventing and / or treating feelings of tightness associated with dry skin.

[0162] General process for the synthesis of compounds of formula (I) or (!')

[0163] The compounds of formula (I) or (!') according to the invention can be obtained for example from the compounds of formula (II) described below and having a terminal carboxylic acid function via a coupling step between the carboxylic acid function of the compound of formula (II) and the amine function of a compound of formula (III).

[0164] The compounds of formula (II) or (II') used to obtain the compounds of formula (I) are as defined below, as well as one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures:

[0165] Formulas (II) and (II') in which:

[0166] - Ri denotes a radical chosen from the group consisting of: a. a hydrogen atom, b) a linear C1-C10 or branched C3-C10 saturated alkyl group optionally substituted by one or more groups, identical or different, chosen from the group consisting of i) -O-R3 and ii) -S-R3 and

[0167] - R2 denotes a linear C1-C12 or branched C3-C[2 or cyclic C3-C8, preferably acyclic and said hydrocarbon group being substituted by a radical -C(O)-OH, and optionally substituted by one or more groups, identical or different, chosen from:

[0168] i) -O-R3,

[0169] ii) -S-R3,

[0170] iii) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more CrC8 alkoxy radicals and

[0171] - R3 denotes a radical chosen from the group consisting of:

[0172] a) a hydrogen atom, and

[0173] b) a linear C1-C10 or branched C3-C10 saturated alkyl group; and

[0174] c) a thiol function or alcohol function protecting group.

[0175] Preferably, in formulas (II) and (II'), Ri represents a hydrogen atom.

[0176] Preferably, the thiopyridinone compound of formula (II) and (II') is selected from the group consisting of compounds II-1 to II-2 below N' Structure Chemical name II-l 0 N-[(2-thmxo-1.2-dihydropyridm-3-yi)carbonyl] glycine

[0177] The thiol or alcohol function protecting groups are for example those mentioned in the document entitled “Protective Groups in Organic Synthesis”, second edition, Theodora W. Greene & Peter GM Wuts, Wiley Interscience Publication, John Wiley & sons INC, 1991, Chapter 2 = Protection of the hydroxyl group including 1,2 and 1,3 diols and chapter 6 = Protection of the Thiol group.

[0178] The compounds of formula (III) denote in particular amino acids H2N- B-COOR5 in which: - B denotes a divalent cyclic or acyclic radical, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, optionally interrupted by one or more heteroatoms or groups, such as an oxygen atom, a sulfur atom, an NR' or (thio)carbonyl group, or their associations such as (thio)ester or (thio)amide(s) -C(X)-N(R')- or -N(R')-C(X)- and / or said group B being optionally substituted, in particular by one or more hydroxy or thiol groups optionally protected by protective groups; and - R5 denotes a protecting group for a carboxylic acid function such as an ester function, in particular a C1-C4 alkyl ester such as an ethyl ester, and - X represents an oxygen atom, sulfur atom, preferably an oxygen atom; and - R' represents a hydrogen atom or a C1-C4 alkyl group such as methyl, preferably a hydrogen atom.

[0179] As examples of compounds of formula (III), mention may be made, for example, of glycine, alanine, beta-alanine, leucine, isoleucine, serine, valine, cysteine, the carboxylic acid function of which is protected, for example, by the protective groups mentioned in the document entitled "Protective Groups in Organic Synthesis", second edition, Theodora W. Greene & Peter GM Wuts, Wiley Interscience Publication, John Wiley & sons INC, 1991, Chapter 5 = Protection of the carboxyl group, in particular by an ester function, more precisely by a Cr-C4 alkyl function such as an ethyl ester.

[0180] When the compounds of formula (III) contain one or more asymmetric carbons, each of them may be of R or S configuration or in racemic form.

[0181] When the compounds of formula (III) denote amino acids, these are preferably of L configuration.

[0182] The coupling between the carboxylic acid function of a compound of formula (II) and the amine function of a compound of formula (III) is carried out using conventional activating or coupling reagents such as carbodiimides such as DCC (= di-cyclohexylcarbodiimide) or water-soluble forms of carbodiimides such as EDC (= N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride), phosphonium salts such as BOP (= benzotriazol-l-yloxy) tris(dimethylamino)phosphonium hexafluorophosphate), PyBOP (=(benzotriazol-l-yloxy)tripyrrolidinophosphonium hexafluorophosphate), PyBROP (= bromotripyrrolidinophosphonium hexafluorophosphate), PyCloP (= chlorotripyr- rolidinophosphonium hexafluorophosphate), or using reagents such as PyClU (= chloro-N,N,N',N'-bis(tetramethylene) formamidinium hexafluorophosphate), N-hydroxysuccinimide, EEDQ (= l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline), CDI (= carbonyldiimidazole), or chloroformates such as ethyl chloroformate or isobutyl chloroformate. When the coupling is carried out using coupling reagents such as carbodiimides, additives such as HOBt (= 1-hydroxybenzotriazole) or N-hydroxysuccinimide can be added during the reaction to limit racemization.

[0183] Preferably, the coupling is carried out with carbodiimides with or without the addition of 1-hydroxybenzotriazole.

[0184] The coupling reaction between a compound of formula (II) or (II') and a compound of formula (III) is carried out in a solvent or a mixture of solvents which are preferably aprotic dipolar, preferably dimethylformamide (DMF), N-methylpyrrolidone (NMP), or aprotic solvents such as 1,2-dimethoxyethane (DME), tetrahydrofuran (THF), dioxane, pure or in a mixture.

[0185] When the compound (III) carries a carboxylic acid function protected by a protective group R5, the coupling reaction can be followed by a step of deprotection of the carboxylic acid function. The deprotection reaction is described in particular in the document entitled "Protective Groups in Organic Synthesis", second edition, Theodora W. Greene & Peter GM Wuts, Wiley Interscience Publication, John Wiley & sons INC, 1991. The conditions of this possible deprotection step are determined by the nature of the protective group R5.

[0186] For example, if the carboxylic acid function of (III) is in ester form (i.e. R5 is for example a C1-C4 alkyl such as ethyl), after coupling, the ester function can be saponified by a preferably mineral base such as sodium hydroxide.

[0187] The invention is illustrated in more detail in the following examples. Examples

[0188] Example 1: Synthesis of the compound of formula (1-1)

[0189] Step 1: Synthesis of compound 3 - N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]ethyl glycinate

[0190] Route 1: via 2-mercaptonicotinic acid

[0191] Thionicotinic acid is introduced into acetonitrile and then carbonyldiimidazole (CDI) into a flask. The resulting mixture is heated to reflux for one hour and then left at room temperature.

[0192] After returning to room temperature, ethyl glycinate hydrochloride is added and then the resulting mixture is heated again at a temperature of 60°C for 3 hours. The mixture is then left at room temperature overnight.

[0193] After the night, the reaction medium is evaporated. The residue is taken up in dichloromethane and washed twice with 2 N HCl.

[0194] The organic phase is dried over anhydrous sodium sulfate then evaporated and purified on silica Dichloromethane 97 / methanol 3.

[0195] The fractions are evaporated.

[0196] A light yellow powder is obtained.

[0197] Route 2: via 2-chloronicotinic acid

[0198] In a three-necked flask, 2-chloronicotinic acid (250.0 g, 1.587 mol) is introduced into ethyl acetate (500 ml) and then SOC12 (210.0 g, 1.761 mol) is added dropwise into the mixture.

[0199] The whole is heated to reflux until complete conversion. Once the reaction is complete, the mixture is cooled to room temperature and is diluted with acetate of ethyl (375ml).

[0200] A solution of ethyl glycinate hydrochloride (265.8g, 1.904mol) diluted in water (400ml) and triethylamine (393.5g, 3.88mol) is then added to the mixture.

[0201] The whole is stirred for a period of 3 to 4 hours and then the ethyl acetate is removed under vacuum.

[0202] The aqueous solution thus obtained is then diluted with water (1250 ml) and then acidified with 3N HCl (25 ml).

[0203] Sodium thiosulfate (1379g, 5.555mol) is then added and the whole is then heated to reflux for 6 hours. After cooling to 10°C, the yellow solid is filtered and washed with water (3 times 750ml).

[0204] The crude product is then treated with carbon black in a 75 / 25 ethanol / water mixture.

[0205] The carbon black is then filtered while hot and the ethanol is evaporated. The whole is cooled to room temperature, then the product is filtered and dried under vacuum.

[0206] A light yellow powder is thus obtained.

[0207] The 1H NMR and mass spectra are consistent with the structure.

[0208] Melting point: 151°C (capillary tube)

[0209] Step 2: Synthesis of the compound N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine from the compound obtained in step 1

[0210] In a three-necked flask are introduced ethyl N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycinate (48 g, 0.317 mol) and a 95% EtOH solution (48 mL).

[0211] The resulting mixture is cooled to 10°C.

[0212] A solution of NaOH (16g) in 144 mL of water is added dropwise into the mixture.

[0213] The organic solvent is evaporated and then the pH of the mixture is adjusted to a value of 3-4. The mixture is then cooled to a temperature between 0 and 10°C and then filtered.

[0214] The product thus obtained is washed with water and dried under vacuum.

[0215] A light yellow powder is obtained.

[0216] The 1H NMR and mass spectra are consistent with the structure.

[0217] Melting point: 241.0-241.8 °C (capillary tube)

[0218] Example 2: Synthesis of compounds 1-1 and 1-2 1-1 compound

[0219] In a 250 mL flask are introduced the (2-mercaptonicotinoyl)glycine obtained in Example 1 (20,000 g, 1 Eq, 94.242 mmol) and DMF (100 mL).

[0220] The whole is stirred until a clear solution is obtained then carbonyldii-midazole (16.809 g, 1.1 Eq, 103.67 mmol) is added in portions.

[0221] The resulting suspension is stirred at a temperature of 20°C until no bubbling occurs (typically for one hour).

[0222] Ethyl glycinate hydrochloride (14.470 g, 1.1 Eq, 103.67 mmol) is then added, and the whole is stirred for one hour at a temperature of 20°C.

[0223] The reaction medium is then added slowly to a 10% aqueous NaHCO3 solution with stirring.

[0224] The suspension obtained is filtered on a frit to yield a solid which is rinsed with distilled water. The solid is dried at a temperature of 50°C under vacuum to obtain ethyl (2-mercaptonicotinoyl)glycylglycinate (compound 1-1) in the form of a yellow powder.

[0225] Spectroscopic analyses are consistent with the indicated structure. Compound 1-2

[0226] In a 250 mL flask are introduced the compound 1-1, as obtained previously, (ethyl (2-mercaptonicotinoyl)glycylglycinate) (13.440 g, 1 Eq, 45.202 mmol) and distilled water (70 mL).

[0227] While stirring, a 50% sodium hydroxide solution is added until a pH value of around 12-13 is reached, keeping the temperature below 25°C. The resulting mixture is stirred for one hour at a temperature of 25°C and then the pH is adjusted to a value of 2 with 37% hydrochloric acid.

[0228] The suspension obtained is filtered on a sintered filter and then the resulting solid is rinsed with water. distilled.

[0229] The solid is dried at 50°C under vacuum to obtain the compound 1-2 (2-mercaptonicotinoyl)glycylglycine in the form of a yellow powder).

[0230] Example 3 - Evaluation of the effect of compound 1-2 on the reinforcement of the barrier function.

[0231] A) Principle of the test

[0232] The study consists of measuring the effect of a treatment of compound 1-2 on the properties of the barrier function on normal human keratinocytes in monolayer.

[0233] The objective of the study is to highlight, by measuring the level of expression of the HBEGF and KRT19 genes (by RT-qPCR), the effects of compound 1-2 from NHEKs keratinocytes in monolayer treated for 24 hours.

[0234] B) Operating mode

[0235] The effect of compound 1-2 was compared with the effect of retinoic acid treatment (0.1 μM) used as a reference condition. The thiopyridinone compound is prepared according to the method described above.

[0236] Treatment of NHEKs keratinocytes

[0237] Normal human epidermal keratinocytes (NHEK) were seeded in 48-well culture plates and then cultured for 3 days in culture medium with renewal of the medium after the first 24 hours of incubation. At the end of the incubation, the culture medium was replaced with test medium (culture medium supplemented with 1.5 mM CaCl2) containing or not (Control), compound 2 at 1 g / L or 0.1 pM retinoic acid (Test Reference) and then the cells were incubated for 24 hours.

[0238] The experiments were carried out in culture duplicates (n=2).

[0239] At the end of the incubation, the media were removed, the cells rinsed in PBS (without CaCl2, without MgCl2). The RNAs were then extracted using a specific kit using magnetic beads and according to the supplier's recommendations (MagMAXTM-96 Total RNA Isolation Kit, Ambion). The RNAs from each replicate were pooled before analysis of their quality and quantity using a LabChip GX bio-analyzer (Perkin Elmer).

[0240] The expression of the selected transcripts was analyzed by 2-step quantitative PCR. Complementary DNAs were first reverse-transcribed from messenger RNAs using the Quantitect® Reverse transcription kit (Qiagen) and according to the supplier's recommendations. Quantitative PCR from cDNAs was then performed using a LightCycler® 480 Real-Time PCR System (Roche) according to the SYBR®Green incorporation method (Roche) described by the supplier and using specific probes (Table 1). The expression of the HBEGF and KRT19 genes was normalized to the expression of 2 housekeeping genes (RPL13A and GAPDH) and a modulation factor relative to the untreated control (Fc) was calculated according to the AACt formula. A modulation is considered positively stimulated when the Fc is greater than 1.5 and significantly inhibited when Fc < 0.5.

[0241] [Tables 1] Reference of the probes used Gene Go ID Referred nee HBEGF QTO1667610 KRT19 3380 QT00C8U37

[0242] C) Results [Tables 2] Bill Markers •V -V .X' .X".'.' ■SWSl 1S! illiil

[0243] Compound 1-2 obtained according to Example 2 (compound according to the invention) stimulated epidermal renewal (HBEGF, KRT19). The results obtained are of the same order as those observed with retinoic acid known as a powerful activator of epidermal renewal.

[0244] Thus, the compounds according to the invention prove effective in epidermal renewal and consequently in improving and strengthening the barrier function, as well as in the prevention and treatment of dry and / or dehydrated skin.

[0245] Example 4 - Cosmetic composition

[0246] A composition in the form of a gel for topical application is prepared comprising: [Tables 3] Compound-[-2« VWenpokfeæ '1111 igllOiiW

[0247] The composition applied to the skin makes it possible to improve the barrier function of the skin.

[0248] (l) Shirakata et al. (“Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing”, Journal of Cell Science 2005 118:2363-2370)

[0249] (2) Brysk et al. (“Gene expression of markers associated with proliferation and differentiation in human keratinocytes cultured from epidermis and from buccal mucosa”, Arch Oral Biol. 1995 Dep; 40(9):855-62).

Claims

Claims

1. Cosmetic use of at least one compound of formula (I) or (!) below, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or of at least one composition comprising it or them: he G) (0 Formulas (I) and (!') in which: - A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, interrupted by one or more (thio)amide(s) -C(X)-N(R')- or (NR')-C(X)- groups, and optionally substituted, in particular by one or more identical or different groups chosen from the group consisting of i) -O-R3 and ii) -S-R3; - M denotes a radical chosen from the group consisting of a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 alkyl group, c) an alkali metal, d) an alkaline earth metal, or e) an ammonium group; preferably M represents a) a hydrogen atom or c) an alkali metal; - Ri denotes a radical chosen from the group consisting of: a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 saturated alkyl group optionally substituted by one or more groups, identical or different, chosen from the group consisting of i) -O-R3 and ii) -S-R3; preferably, R1 represents a hydrogen atom; - R3 denotes a radical chosen from a) a hydrogen atom, b) a linear C1-C10 or branched C3-C10 saturated alkyl group; preferably, R3 represents a hydrogen atom; -X represents an oxygen atom, a sulfur atom, preferably an oxygen atom,

2.

3.

4. - R' represents a hydrogen atom or a C1-C4 alkyl group, in particular C1, preferably R' represents a hydrogen atom; to improve the barrier function of the skin. Use according to claim 1, characterized in that Ri represents a) a hydrogen atom. Use according to claim 1 or 2, characterized in that A represents a (C2-C6)alkylene group, linear or branched, preferably linear; said chain A being interrupted by a group -C(X)-N(R')- with X and R' as defined in claim 1, more particularly interrupted by a group -C(O)-N(H)-; in particular A represents a group CH2-C(O)-N(R')-CH2- or -CH2-N(R')-C(X)-CH2- with X and R' as defined in claim 7, preferably A represents a group -CH2-C(O)-N(H)-CH2-. Use according to any one of the preceding claims, characterized in that the compound(s) of formula (I) or (!') is or are chosen from the group consisting of the compounds of formula (IA) or (IB) below, their acid or base salts, organic or mineral, their solvates, such as hydrates, their optical isomers, their geometric isomers and their mixtures: (IA) (IB) Formulas (IA) and (IB) in which: - Ra and Rb denote, independently of each other, a hydrogen atom or a C1-C4 alkyl radical optionally substituted by one or more hydroxyl (OH) or thiol (SH) radicals; and - n and m independently denote an integer equal to 1 or 2 or 3; preferably n and m are identical and are equal to 1; - M has the same meaning as for the compounds of formula (I) or (I'); particularly M represents a hydrogen atom, an alkali metal, or an alkyl group, linear or branched, CrC4 alkyl such as methyl or ethyl, of preferably a hydrogen atom or an alkali metal such as sodium or potassium.

5. Use according to any one of the preceding claims, characterized in that the compound(s) of formulae (I) or (I'), the compounds of formulae (IA) or (IB) is or are chosen from the compounds of formulae (la) to (li) or (la) to (i) below as well as their tautomers, their organic or mineral acid or base salts, their solvates, such as their hydrates, their optical isomers, their isomers

6. with M as defined above, particularly M represents a hydrogen atom, an alkali metal, or a linear or branched C1-C4 alkyl group such as methyl or ethyl, more preferably a hydrogen atom or an alkali metal such as sodium or potassium. Use according to any one of the preceding claims, characterized in that the compounds of formula (I) or (I'), the compounds of formulas (IA) or (IB) are chosen from the compounds of formulas (1-1) or (1'1) or (1-2) or (1'2), below as well as their acid or base salts, organic or inorganic, in particular their sodium or potassium salts, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures: O .. oa H Ci H :) ï H / --s j'-r AA . < h ¥ ' CAI :î A tr OH i) JH â j HAHH SH (Tl) 0'2) A « x Ji  aÛ (YY r 'f ' “ " (M) “ (1-2)

7. Use according to any one of the preceding claims for increasing the renewal of the epidermis, for improving the surface condition of the skin, for preventing and / or treating roughness or alteration of the micro-relief of the skin, and / or for reducing the number and / or size of fine lines on the surface of the skin.

8. Use according to any one of the preceding claims for preventing and / or treating cosmetic signs associated with sensitive or dry skin.

9. Cosmetic treatment process for improving the barrier function of the skin comprising a step of applying to the skin at least one compound of formula (I) or (!), as defined according to any one of claims 1 to 6, and / or one of their acid or base salts, organic or mineral, their solvates, such as their hydrates, their optical isomers, their geometric isomers and their mixtures, or at least one composition containing it or them.

10. Cosmetic treatment method comprising a step of applying to the skin at least one compound of formula (I) or (!') as defined in any one of claims 1 to 6 or a cosmetic composition comprising at least one such compound, to increase the renewal of the epidermis, to improve the surface condition of the skin, to prevent and / or treat roughness or alteration of the micro-relief of the skin, to reduce the number and / or size of fine lines on the surface of the skin and / or to prevent and / or treat the cosmetic signs associated with sensitive or dry skin.