ACTIVE COMPOUND DELIVERY COMPOSITION

Abstract

ACTIVE COMPOUND DELIVERY COMPOSITION The invention relates to a composition comprising A) a thiopyridinone compound; B) a C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound, having at most one C=C bond. Figure for abstract: None

Description

Title of the invention: COMPOSITION FOR DELIVERING ACTIVE COMPOUND Technical field

[0001] The present invention relates to a composition for stimulating the delivery of active compounds into the skin. CONTEXT

[0002] Skin care, for example skin lightening, always attracts great interest among consumers. Accordingly, the ultimate goal of the cosmetics industry has always been to deliver highly effective products to consumers with skin benefits such as moisturizing, lightening, cleansing, and others.

[0003] For effective delivery, different forms of products are used. To date, it is still sometimes difficult to deliver hydrophilic actives into the deep skin (round dermal junction). In particular, it is known that certain thiopyridinone compounds exhibit good depigmenting activity, even at low concentrations, see for example documents WO2012080075 and WO2017 / 102349. The thiopyridinone compound can exhibit strong depigmenting or lightening effects by reducing melanin production.

[0004] There is therefore a need for a composition for stimulating the delivery of active compounds, for example thiopyridinone compounds, into the skin. Summary of the invention

[0005] The inventors have unexpectedly discovered that a composition comprising the components: A) a compound of formula (I) or (I'), which can be considered as a thiopyridinone compound, or their salts, their optical isomers, their racemates, and / or their solvates such as hydrates and their derivatives, alone or in mixture; B) a C12-20 fatty compound having at most one C=C bond, can satisfy the need. (I) (F)

[0006] Formulas (I) and (!') in which:

[0007] Ri denotes a radical chosen from:

[0008] a) a hydrogen atom;

[0009] b) a linear saturated C1-C10 or C3-C10 branched alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from:

[0010] i) -O-R3

[0011] ii)-S-R3;

[0012] R2 denotes a radical chosen from:

[0013] a) a hydrogen atom;

[0014] b) a linear or branched C3-Ci2 or cyclic C3-C8 saturated hydrocarbon group, optionally substituted by one or more groups, which may be the same or different, chosen from:

[0015] i) -O-R3

[0016] ii) -S-R3

[0017] iii) -C(O)-O-R3;

[0018] iv) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals;

[0019] c) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more CrC8 alkoxy radicals

[0020] R3 denotes a radical chosen from:

[0021] a) a hydrogen atom;

[0022] b) a linear C1-C10 or branched C3-C10 saturated alkyl group;

[0023] Compound (!') is the tautomeric form of compound (I) when a tau- equilibrium tomeric exists according to the following scheme:

[0024] According to one embodiment of the invention, Ri represents a hydrogen atom.

[0025] According to another embodiment of the invention, Ri represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C1-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl. In particular, said alkyl group of Ri is not substituted.

[0026] According to one embodiment of the invention, R2 represents a hydrogen atom.

[0027] According to another embodiment of the invention, R2 represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C1-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R2 being unsubstituted.

[0028] According to another embodiment of the invention, R2 represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group being substituted by one or more groups chosen from i), ii), iii) and iv) as defined hereinbefore. Preferably, said alkyl group being substituted by one or more groups chosen from i), ii) and iii), more preferably by one or more groups chosen from i) and iii), better substituted by a group iii) such as carboxy.

[0029] Another variant for the radical R2 is that said alkyl group is substituted by a group iv) in particular substituted by a phenyl group.

[0030] According to another embodiment of the invention, R2 represents a cycloalkyl group (C3-C8), preferably a cycloalkyl group (C5-C7) such as cyclohexyl.

[0031] According to another embodiment of the invention, R2 represents a C5-C12 aryl group optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals, preferably a phenyl group in particular unsubstituted.

[0032] According to one embodiment, R3 represents a hydrogen atom.

[0033] According to another embodiment, R3 represents a linear C1-C10 or branched C3-C10 saturated alkyl group; in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group such as the methyl group. DESCRIPTION OF DRAWINGS

[0034] [Fig-1] [Fig.l] shows the distribution of compound 20 in the test samples of Ex. 1 and some others;

[0035] [Fig.2] [Fig.2] shows the distribution of TXA in the test samples of Ex.2 and some others;

[0036] [Fig.3] [Fig.3] shows the distribution of compound 20 in the test samples of Ex. 10-11 and EC.3 by confocal Raman microscope; and

[0037] [Fig.4] [Fig.4] shows the distribution of TXA in the test samples of the Ex. 10-11 and EC.3 via a confocal Raman microscope. MODES OF EMBODIMENT OF THE INVENTION

[0038] Throughout the description, including the claims, the term "comprising one" shall, unless otherwise stated, be understood as being synonymous with "comprising at least one". Furthermore, the expression "at least one" as used in this description is equivalent to the expression "one or more".

[0039] For the purposes of the present invention, and unless otherwise indicated:

[0040] a "linear or branched C3-Ci2 saturated hydrocarbon group" is equivalent to a "linear (C1-Ci2)alkyl or branched (C3-Ci2)alkyl group" which corresponds to a linear or branched C3-Ci2 saturated hydrocarbon group, and preferably a linear or branched C3-Ci0 hydrocarbon group, more preferably a linear or branched C3-Ci6 hydrocarbon group; preferably, the linear or branched groups may be chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl.

[0041] More preferably, the linear or branched saturated alkyl groups may be chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl and octyl groups, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl.

[0042] - a saturated C3-C8 hydrocarbon cyclic group is a mono cycloalkyl group or bicyclic containing from 3 to 8 carbon atoms, in particular a monocyclic C5 to C7 cycloalkyl group such as the cyclohexyl group,

[0043] - an "alkoxy radical" is an alkyloxy radical for which the alkyl radical is a linear or branched hydrocarbon radical in CrCi6 and preferentially in CrC8;

[0044] - when the alkoxy group is optionally substituted, this implies that the group alkyl is optionally substituted as defined above;

[0045] - an "aryl" group represents a carbon-based, monocyclic or bi cyclic, fused or not, comprising from 5 to 12 carbon atoms, preferably from 6 to 10 carbon atoms, and in which at least one cycle is aromatic; preferably, the aryl radical is a phenyl, biphenyl, naphthyl group, more preferably a phenyl group;

[0046] - the term "at least one" is equivalent to the term "one or more"; and

[0047] - the term "inclusive" for a concentration range means that the limits of this range are included in the defined range.

[0048] Salts of compounds of formula (I), (I'), (II) or (II1) as defined herein include conventional non-toxic salts of said compounds, such as those formed from an organic or inorganic acid or an organic or inorganic base.

[0049] As salts of the compounds of formula (I), (I'), (II) or (II1), mention may be made of:

[0050] the salts obtained by addition of the compound of formula (I) or (II) to:

[0051] - a mineral base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, and sodium, potassium or calcium carbonate or hydrogen carbonate for example;

[0052] or

[0053] - an organic base such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine. This primary, secondary or tertiary alkylamine may comprise one or more nitrogen and / or oxygen atoms and may therefore comprise, for example, one or more alcohol functions; in particular, 2-amino-2-methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol, 3-(dimethylamino)propylamine may be mentioned.

[0054] Mention may also be made of amino acid salts, for example lysine, arginine, guanidine, glutamic acid and aspartic acid. Advantageously, the salts of the compounds of formula (I) or (II) (when they comprise a carboxy group) may be chosen from alkali or alkaline-earth metal salts such as sodium, potassium, calcium or magnesium salts and ammonium salts.

[0055] - An "organic or inorganic acid salt" is more particularly chosen from salts selected from a salt derived from i) hydrochloric acid HCl, ii) hydrobromide acid HBr, iii) sulfuric acid H2SO4, iv) alkylsulfonic acids: Alk-S(O)2OH such as methanesulfonic acid and ethanesulfonic acid; v) arylsulfonic acids: Ar-S(O)2OH such as benzenesulfonic acid and toluenesulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid; x) alkoxysulfinic acids: Alk-OS(O)OH such as methoxysulfinic acid and ethoxysulfinic acid; xi) aryloxysulfinic acids such as tolueneoxysulfinic acid and phenoxysulfinic acid; xii) phosphoric acid H3PO4; xiii) acetic acid CH3 C(O)OH; xiv) triflic acid CF3SO3H; and xv) tetrafluoroboric acid HBF4;

[0056] - Acceptable solvates of the compounds described in the present invention include take the classical solvates such as those formed during the preparation of said compounds due to the presence of solvents. Examples include solvates due to the presence of water or linear or branched alcohols, such as ethanol or isopropanol.

[0057] - The optical isomers are in particular the enantiomers and the diastereoisomers.

[0058] Preferably, the "keratinous material" according to the present invention is the skin. By "skin", we mean all the skin of the body. Still preferably, the keratinous material is the face or the neck, more particularly the face.

[0059] In the application, unless specifically stated otherwise, quantities, contents, parts and percentages are expressed on a weight basis.

[0060] In the application, a numerical range is defined with a lower limit and an upper limit if necessary, such that one or more lower limits and one or more upper limits are given to form a range optionally with one or more preferred ranges. A given range may be defined by selecting a lower limit and an upper limit that define the bounds of the given range. All ranges defined in this manner are inclusive and combinable, i.e., any lower limit may be combined with any upper limit to form a range, provided that both the lower and upper limits are provided to modify the same subject. For example, where ranges of 60-110 and 80-120 are indicated for a specific subject, it is to be understood that the ranges 60-120 and 80-110 are also contemplated and encompassed. Furthermore, if the indicated lower limits are 1 and 2 and the upper limits are 3, 4, and 5, the following ranges are all foreseeable and within the scope of this disclosure: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5.

[0061] Apart from the working examples, or unless otherwise indicated, all numbers expressing amounts of components and / or reaction conditions should be understood as being modified in all cases by the term "about", with a meaning conventionally known in the art, for example, to within 10% of the number indicated (such as "about 10%" means 9% - 11% and "about 2%" means 1.8% - 2.2%). Component A)

[0062] The composition according to the invention comprises a compound of formula (I) or (!') below or tautomer (!') below or their salts, their optical isomers, their racemates, and / or their solvates such as hydrates and their derivatives, alone or as a mixture, as component A): (I) (D

[0063] Formulas (I) and (!') in which:

[0064] Ri denotes a radical chosen from:

[0065] a) a hydrogen atom;

[0066] b) a linear saturated C1-C10 or C3-C10 branched alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from:

[0067] i) -O-R3

[0068] ii)-S-R3;

[0069] R2 denotes a radical chosen from:

[0070] a) a hydrogen atom;

[0071] b) a linear or branched C3-Ci2 or cyclic C3-C8 saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from:

[0072] i) -O-R3

[0073] ii) -S-R3

[0074] iii) -C(O)-O-R3;

[0075] iv) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals;

[0076] c) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more CrC8 alkoxy radicals

[0077] R3 denotes a radical chosen from:

[0078] a) a hydrogen atom;

[0079] b) a linear C1-C10 or branched C3-C10 saturated alkyl group;

[0080] Compound (!') is the tautomeric form of compound (I) when a tau- equilibrium tomeric exists according to the following scheme:

[0081] According to one embodiment of the invention, Ri represents a hydrogen atom.

[0082] According to another embodiment of the invention, Ri represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C1-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl. In particular, said alkyl group of Ri is not substituted.

[0083] According to one embodiment of the invention, R2 represents a hydrogen atom.

[0084] According to another embodiment of the invention, R2 represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R2 being unsubstituted.

[0085] According to another embodiment of the invention, R2 represents a linear or branched (C1-C10) alkyl group, in particular a linear or branched (C1-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably preferably methyl or ethyl; said alkyl group being substituted by one or more groups selected from i), ii), iii) and iv) as defined hereinbefore. Preferably, said alkyl group being substituted by one or more groups selected from i), ii) and iii), more preferably by one or more groups selected from i) and iii), better substituted by a group iii) such as carboxy.

[0086] Another variant for the radical R2 is that said alkyl group is substituted by a group iv) in particular substituted by a phenyl group.

[0087] According to another embodiment of the invention, R2 represents a cycloalkyl group (C3-C8), preferably a cycloalkyl group (C5-C7) such as cyclohexyl.

[0088] According to another embodiment of the invention, R2 represents a C5-C12 aryl group optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals, preferably a phenyl group in particular unsubstituted.

[0089] According to one embodiment, R3 represents a hydrogen atom.

[0090] According to another embodiment, R3 represents a linear C1-C10 or branched C3-C10 saturated alkyl group; in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group such as the methyl group.

[0091] Preferably, the compounds of formula (I) and the tautomer (!') or their salts, their optical isomers, racemates, and / or solvates such as hydrates and their derivatives, alone or in mixture, as component A);

[0092] have the following meanings:

[0093] Ri denotes a radical chosen from:

[0094] a) a hydrogen atom;

[0095] b) a linear C1-C6 or C3-C6 branched saturated alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from:

[0096] i) -O-R3

[0097] ii)-S-R3;

[0098] preferably optionally substituted with one or more groups i)

[0099] R2 denotes a radical chosen from:

[0100] a) a hydrogen atom;

[0101] b) a linear C1-C10 or branched C3-C10 or cyclic C3-C8 or C5-C6 saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from:

[0102] i) -O-R3

[0103] ii) -SR-,

[0104] iii) -C(O)-O-R3;

[0105] iv) a phenyl group optionally substituted by one or more hydroxyls and / or by one or more C1-C4 alkoxy radicals such as methoxy;

[0106] preferably substituted by one or more groups chosen from i) and iii), preferentially iii) such as carboxy

[0107] R3 denotes a radical chosen from:

[0108] a) a hydrogen atom;

[0109] b) a linear C1-C6 or branched C3-C6 saturated alkyl group;

[0110] Preferably, the compounds of formula (I) and the tautomer (I1) or their salts, their optical isomers, racemates, and / or solvates such as hydrates and their derivatives, alone or in mixture;

[0111] have the following meanings:

[0112] Ri denotes a radical chosen from:

[0113] a) a hydrogen atom;

[0114] b) a linear saturated C1-C4 or C3-C4 branched alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from i) -OR3jplus preferably unsubstituted;

[0115] R2 denotes a radical chosen from:

[0116] a) a hydrogen atom;

[0117] b) a linear C1-C10 or branched C3-C10 or cyclic C3-C8 or C5-C6 saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from:

[0118] i)-O-R3

[0119] iii) -C(O)-O-R3;

[0120] iv) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C4 alkoxy radicals;

[0121] R3 denotes a radical chosen from:

[0122] a) a hydrogen atom;

[0123] b) a linear C1-C4 or branched C3-C4 saturated alkyl group such as methyl or ethyl.

[0124] Preferably, the compounds of formula (I) and the tautomer (!) or their salts, their optical isomers, racemates, and / or solvates such as hydrates and their derivatives, alone or as a mixture;

[0125] have the following meanings:

[0126] Ri is a hydrogen atom; and

[0127] R2 denotes a radical chosen from:

[0128] a) a hydrogen atom;

[0129] b) a linear C1-C5 or branched C3-C5 or cyclic saturated hydrocarbon group in C3-C8 as in C5-C6, optionally substituted by one or more groups, which may be the same or different, chosen from v) -C(O)-O-R3, preferably substituted by a group iii) -C(O)-O-R3;

[0130] R2 is even more preferably a linear saturated hydrocarbon group in CrC4 or branched in C3-C4 substituted by a group iii) -C(O)-OR3.

[0131] According to another preferred embodiment, the compounds of formula (I) and the tautomer (I1) are chosen from the compounds of formula (II) as well as their tautomers, their salts, their solvates and their optical isomers, and their racemates, alone or as a mixture: (II) (II')

[0132] Formulae (II) and (II1) without which RI and R3 have the same meaning as for the compounds of formula (I) and (I1) and X denotes an alkylene radical -(CH2)n- with n an integer ranging inclusively from 1 to 10, preferably ranging from 1 to 6, more preferably ranging from 1 to 4, such that 1, preferably R3 represents a hydrogen atom.

[0133] Preferably, the compounds of formula (I), the following compounds are preferably used, and their tautomer (I1) or their salts, their optical isomers, racemates, and / or solvates such as hydrates and their derivatives, alone or in mixture; No. Structure Chemical name CAS No. 1 B i HH N-ethyl-2-thioxo-1,2-dihy dropyridine- 3 -c arboxa mide 91859-75-5 2 V A-- N-methyl-2-thioxo-1,2-dihy dropyridine- 3 -c arboxa mide 91859-74-4 3 -x.--' 'V.--' N-octyl-2-thioxo-1,2-dihydropyridine- 3 -c arboxa mide 91859-77-7 4 s SS < x '7 N-benzyl-2-thioxo-1,2-dihydropyridine- 3 -c arboxa mide 91859-79-9 5 .<------\ ........w 's N-phenyl-2-thioxo-1,2-dihydropyridine- 3 -c arboxa mide 104857-16-1 6 HJ j X' ' ''N"' HJHH N-cyclohexyl-2-thioxo-1,2-dihydropyridine- 3 -c arboxa mide 91859-78-8 7 :i ]SL Ü N-[2-(4-methoxyphenyl)ethyl]-2-thioxo-1,2-dihydrop yridine-3-carboxamide 923682-88-6 8 i HH * w ,*'K, „X. Y'" 'Y 'w <7 ON - (2-methyl Ipropy 1)-2-thio xo-1,2-dihydropyridine-3-c arboxamide 1100027-79- 9 9 N-pentyl-2-thioxo-1,2-dihy dropyridine-3-c arboxa mide 330667-57-7 10 N-nonyl-2-thioxo-1,2-dihy dropyridine- 3 -c arboxa mide 1031149-44- 6 11 H 3 | À \ H 'Nx 'OH S’ N-(2-hydroxyéthyl)-2-thio xo-1,2-dihydropyridine-3-c arboxamide 12 1 '"■‘y'"' N,N-diéthyl 2-mercaptonicotinamide 13 H L>s ^1---.. :: \ : S < —-OH s Yk. N-éthyl-N-(2-hydroxyéthyl )-2- thioxo-1,2-dihydropyridine -3- carboxamide 14 |i ür! N-(2,3-dihydroxypropyl)-2 thioxo-1,2-dihydropyridine -3- carboxamide 15 N-( 1,3-dihydroxypropan-2-yl)-2-thioxo-1,2-dihydropy ridine-3-carboxamide 16 X^^X % H / < N- [(2-thioxo-1,2-dihydrop yridin-3-yl)carbonyl]alanin ate d'éthyle 17 J N- [(2-thioxo-1,2-dihydrop yridin-3-yl)carbonyl]phény 1 alaninate d'éthyle 18 x^y xnz v-' x ^x :'; T 1 CM.. Ethyl N-methyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbon yi] glycinate 19 Ethyl N-[(2-thioxo-1,2-dihydrop yridin-3-yl)carbonyl]glycin ate 20 x,.^ .x^x -XX N-[(2-thioxo-1,2-dihydrop yridin-3-yl)carbonyl]glycin e 21 ~ / =y \ / FA i» U c N-methyl-N-[(2-thioxo-1,2 dihydropyridin-3-yl)carbon yi] glycine 22 X. XX xx ï ï N,N-bis(2-hydroxyethyl)-2 thioxo-1,2-dihydropyridine -3- carboxamide 23 ..J'-:... N-(3-methoxypropyl)-2-thi OXO- 1,2-dihydropyridine-3-carboxamide 24 f-:XA' N-butyl-2-thioxo-1,2-dihy dropyridine- 3 -c arboxa mide

[0134] Among these compounds, the following compounds are more particularly preferred: No. Structure Chemical Name CAS No. 1 AA <a a^ h n-éthyl-2-thioxo-1,2-dihydropyridine-3-carboxami de 91859-75-5 2 'a'-.- zx    x\     n-méthyl-2-thioxo-1,2-dihydropyridine-3-carboxami 91859-74-4 4 xx.       xx, n-benzyl-2-thioxo-1,2-dihydropyridine-3-carboxami 91859-79-9 6 q       $       x            §            1 a z aa ax :        h sm n-cyclohexyl-2-thioxo-1,2-dihydropyridine-3-carboxami 91859-78-8 7 r * n-[2-(4-méthoxyphényl)éthy l]-2- thioxo-1,2-dihydropyridine-3 carboxamide 923682-88- 9 h ■ ? a'1'' xi n-pentyl-2-thioxo-1,2-dihydropyridine-3-carboxami 330667-57- 11 0 f    ’yy      >4«. / x î ' GH A N" SX H N-(2-hydroxyéthyl)-2-thioxo -1,2-dihydropyridine-3-carboxami de 12 / " \ \ ,».«>. / / ’v / z J r / d N,N-diéthyl 2-mercaptonicotinamide 14 vX'' X\ •t • : > N-(2,3-dihydroxypropyl)-2-t hioxo- 1,2-dihydropyridine-3-carbo xamide 15 x-v M. ,ûH Yfj..-'" ’V^ N-( 1,3-dihydroxypropan-2-yl )-2- thioxo-1,2-dihydropyridine-3 carboxamide 16 "N-' '-SH / Ethyl N- [(2-thioxo-1,2-dihydropyridi n-3- yl)carbonyl]alaninate 17 fi 1 XYY Ethyl N- [(2-thioxo-1,2-dihydropyridi n-3- yl)carbonyl]phenyl alaninate 18 N "X''*' ! yX, Ethyl N-methyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl] glycinate 19 yY N- [(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine 21 Y Yy xx É 'Xx ch H N-methyl-N- [(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl] glycine

[0135] More preferably, among these compounds, the following compounds are more particularly preferred: No. Structure Chemical Name CAS No. 1 f. YN ■ H N-ethyl-2-thioxo-1,2-dihydropyridine-3-carboxami of 91859-75-5 9 x"' 'X"'' S"' x,x" ;< < X N-pentyl-2-thioxo-1,2-dihydropyridine-3-carboxami of 330667-57- 7 16 îi :W3 Vv:" WXH ? «sc Ethyl N- [(2-thioxo-1,2-dihydropyridi n-3- yl)carbonyl]alaninate 18 "" XNX ,Ax. <X à. xX X-Y i Q-t, Éthyl N-méthyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl ] glycinate 19 J V< ' S / ï :¾ 3 N- [(2-thioxo-1,2-dihydropyri din-3-yl)carbonyl]glycinate d'éthyle 20 > < N-[(2-thioxo-1,2-dihydropyri din-3-yl)carbonyl]glycine 21 QH N-methyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine

[0136]

[0137] Even more preferably, among these compounds, the following compounds are more particularly preferred: No. Structure Chemical Name CAS No. 18 Ethyl N-methyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycinate 19 H Ethyl N-[(2-thioxo-1,2-dihydropyridi n-3-yl)carbonyl]glycinate 20 cA'y' N-[(2-thioxo-1,2-dihydropyri din-3-yl)carbonyl]glycine 21 XK H N-methyl-N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine In a most preferred embodiment, the compound according to the present invention is as follows: 20 N-[(2-thioxo-1,2-dihydropyri din-3-yl)carbonyl]glycine

[0138] All compounds can be obtained by a chemical process known to those skilled in the art, from commercially available reagents. For example, the synthesis process disclosed in European patent application EP3 390 363 can be used.

[0139] Compound 20, N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine, which may also be named 3-carboxymethylaminocarbonyl-2-thiopyridinone, is a typical representative of the thiopyridinone compounds useful according to the present invention. Solubility of Component A)

[0140] By careful study, the inventors believe, without being constrained by any known theory, that the compound of formula (I) or (I'), in particular for example compound 20, may be a typical representative of the thiopyridinone compounds useful according to the present invention mainly due to a specific log P thereof.

[0141] The term "log P" is a measure known in the art to distinguish between a "hydrophilic" and "hydrophobic" compound. The value of log P can be determined by any method conventionally known in the art. For "log P", P is a partition coefficient, representing the ratio of the equilibrium concentration of a compound in an organic phase to that in an aqueous phase. Typically, a P value for a compound between octanol and water is used in the art. Therefore, a hydrophilic compound generally has a log P value of less than 3.5, less than 1.0, or typically less than about -0.5, where P is the partition coefficient of the compound between octanol and water; and a hydrophobic compound generally has a log P of 3.5 or greater, or typically 5.0 or greater.

[0142] Based on compound 20, the inventors make a broad study and determine that compound 20 is particularly useful mainly because it has a log P falling in the range of -1.6 to 0.5, preferably -0.5 to 0.2. Therefore, thiopyridinone compounds of formulas (I) or (!') having a log P of -1.6 to 0.5 are particularly preferred for use as component A).

[0143] Component A), for example compound (I), (!'), (II) and / or (II1), in particular a compound having a log P of -1.6 to 0.5, may be present in an amount ranging for example from 0.01% to 10% by weight, preferably from 0.1% to 5% by weight, in particular from 0.5% to 3% by weight, relative to the total weight of the composition.

[0144] Component A'), additional hydrophilic active compounds

[0145] As stated above, compound 20 is particularly useful in particular because it has a log P ranging from -1.6 to 0.5. In other words, various additional cosmetically acceptable hydrophilic active compounds needing to be delivered to the skin may be used as component A') according to the present invention or used in combination with component A); as long as the additional hydrophilic active compound has a log P between -1.6 and 0.5.

[0146] According to one embodiment of the invention, component A') preferably carries a carboxyl group, which is in particular a carboxylic acid or an ester / salt thereof, preferably a carboxylic acid.

[0147] For example, among others, tranexamic acid (TXA) is a typical example of component A'). According to one embodiment of the invention, TXA is used as component A') together with compound 20 as component A).

[0148] In addition, water-soluble vitamins may be used in the composition as the active compound of component A'). Useful examples of vitamin include vitamin C (ascorbic acid), the B group of vitamins (e.g., vitamin B5 (panthenol), vitamin B3 (niacinamide), vitamin B1 and vitamin B2), nicotinic acid, folic acid, pantothenic acid, derivatives of these vitamins (especially esters) and mixtures thereof.

[0149] Component A), i.e. the thiopyridinone compound of formula (I) or (!), is a derivative of niacinamide. For the purposes of the invention, other derivatives of the latter known to be useful as active compounds for cosmetic use, in particular for the skin, may also be used.

[0150] Component A') having a log P of -1.6 to 0.5, may be present in an amount ranging for example from 0.01% to 20% by weight, preferably from 0.05% to 10% by weight, or preferentially from 0.1% to 5% by weight, relative to the total weight of the composition.

[0151] Component B), a C12-20 fatty compound having at most one C=C bond

[0152] The composition according to the invention may comprise a C12-20 fatty compound having at most one C=C double bond, i.e. having a C=C bond or having no C=C bond, provided that when component B) is a fatty acid, it is a C12-C16 fatty acid.

[0153] By "fatty compound" is meant organic compounds which are insoluble in water at ordinary temperature (25°C) and atmospheric pressure (760 mmHg) (solubility less than 5%, preferably 1% and even more preferably 0.1%). In addition, fatty compounds are generally soluble in organic solvents under the same temperature and pressure conditions, for example chloroform, ethanol, benzene or decamethylcyclopentasiloxane.

[0154] The fatty compounds are notably chosen from fatty alcohols, fatty acids, fatty acid esters, and / or fatty alcohol esters. According to one embodiment of the invention, the fatty compound of component B) according to the invention does not comprise any additional heteroatom other than the C, H and O atoms.

[0155] According to the present invention, it is believed that the use of the specific component B) in combination with component A) and / or A') can promote the delivery of component A) and / or A') into the skin. Without being limited to any known theory, it is deduced that an appropriate length of the carbon chain is important for delivery. Too long a carbon chain may result in a decrease in the delivery effect, while too short a carbon chain may be too volatile to be formulated into a useful product. By studying the match with component A) and / or A') and by experiments, it is believed that the useful component B) may be a C12-20 fatty compound, preferably a C12-18 fatty compound, or preferentially a C12-16 fatty compound.

[0156] According to one embodiment of the invention, an exemplary component B) may carry a C1-C6 alkyl branch.

[0157] Furthermore, it is surprising to see that for the purposes of the present invention, the useful fatty compound may preferentially have at most one C=C double bond, for example, have no C=C bonds. Therefore, a C12-20 fatty compound, preferably a C12-18 fatty compound, or preferably a C12-16 fatty compound, having a saturated carbon chain may be particularly useful.

[0158] The fatty alcohols that can be used in the composition of the invention are not oxyalkylenated. They are saturated or unsaturated, linear or branched and comprise from 12 to 20 carbon atoms. Mention may be made of lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol and their mixture (cetyl-stearyl alcohol), octyldodecanol, butyloctanol, or hexyldecanol.

[0159] The fatty acid that can be used in the composition of the invention includes a C12 to C16 fatty acid, such as lauric acid or lauroleic acid (C12), myristic acid or myristelaidic acid (C14), palmitic acid or palmitoleic acid (C16).

[0160] Useful esters are esters of saturated or unsaturated, linear or branched, aliphatic mono- or polyacids and of saturated or unsaturated, linear or branched, aliphatic mono- or polyalcohols, provided that the total carbon number of the esters is between 12 and 20.

[0161] Among the monoesters, mention may be made of cetyl lactate; C12-C15 alkyl lactate; lauryl lactate; oleyl lactate; octyl octanoate; isononyl isononanoate; octyl iso-nonanoate; 2-ethylhexyl isononate; octyl pelargonate; ethyl and isopropyl palmitates, alkyl myristates such as butyl myristate, ethyl laurate or oleate.

[0162] Among the polyesters, we can cite: diethyl sebacate; diisopropyl sebacate; diisopropyl adipate; di-n-propyl adipate; dioctyl maleate; glyceryl undecylenate; propylene glycol dicaprylate; triisopropyl citrate; glyceryl trilactate.

[0163] Preferably, no C18 or higher fatty acid is included in the composition of the present invention.

[0164] Advantageously, the content of fatty compound(s) ranges from 0.01% to 30% by weight, preferably from 0.1% to 10% by weight, or from 0.5% to 5% by weight relative to the total weight of the composition. Component C), surfactant

[0165] The composition according to the present invention may comprise a surfactant as optional component C), for example a non-ionic surfactant, or a mixture thereof. According to the present invention, any conventional surfactant may be used, as long as it is compatible with the other components of the composition, in particular with components A), A') and / or B), in particular those benefiting from, or at least not negatively affecting, the delivery effect of component A) and / or A') into the skin.

[0166] Among the useful nonionic surfactants, mention may be made of esters of polyols and fatty acids with a saturated or unsaturated chain, as well as their oxyalkylenated derivatives, i.e. derivatives containing oxyethylenated and / or oxypropylenated units, such as glyceryl esters and their oxyalkylenated derivatives; polyethylene glycol esters and their oxyalkylenated derivatives; sorbitol esters and their oxyalkylenated derivatives; sugar esters (sucrose, glucose or alkylglucose) and their oxyalkylenated derivatives; fatty alcohol ethers; sugar ethers and their mixtures.

[0167] Glyceryl esters of fatty acids which may in particular be mentioned include glyceryl stearate (glyceryl monostearate, distearate and / or tristearate).

[0168] Polyethylene glycol esters of fatty acids that may be mentioned in particular include polyethylene glycol monostearate 40 EO (CTFA name: PEG-40 stearate).

[0169] Mixtures of these surfactants may also be used.

[0170] In accordance with the solubility of component A) and the nature of component B), as well that with the medium / solvent to be used, component C), when used, may preferably have an HLB value of 2-20, preferably 8-20, or preferably 10-18.

[0171] The non-ionic surfactant may be present in the composition according to the present invention in an amount of 0.1% to 15% by weight, such as 0.15% to 10% by weight, relative to the total weight of the composition. Component D), Medium / solvent

[0172] The composition according to the invention may advantageously comprise at least one medium / solvent, in particular water and / or an organic medium / solvent, for use as optional component D). Water

[0173] The composition according to the invention may advantageously comprise water in various amounts. For low viscosity applications of the composition, for example in the form of a leave-in lotion, a relatively large amount of water may be used. For example, the water is used in a content greater than or equal to 40% by weight relative to the total weight of the composition. The water content in the low viscosity composition according to the invention preferably ranges from 40% to 99% by weight, more preferably from 50% to 90% by weight, or from 60% to 80% by weight, relative to the total weight of the composition.

[0174] For high viscosity applications of the composition, for example in the form of a leave-in cream, a relatively smaller amount of water may be used. The high viscosity composition according to the invention advantageously comprises water in a content of less than or equal to 40% by weight relative to the total weight of the composition. The water content in the high viscosity composition according to the invention preferably ranges from 10% to 40% by weight, more preferably from 15% to 35% by weight, or from 20% to 30% by weight, relative to the total weight of the composition. Medium / organic solvent

[0175] The composition according to the invention may also comprise one or more organic media / solvents, preferably water-soluble organic media / solvents (solubility greater than or equal to 5% in water at 25°C and at atmospheric pressure; or having a log P of -3.0 to 3.5, preferably of -3.0 to 0.5).

[0176] According to a preferred embodiment of the invention, the composition may comprise at least one organic medium / solvent.

[0177] Examples of organic media / solvents that may be cited include monoalcohols or diols, linear or branched, and preferably saturated, comprising 2 to 10 carbon atoms, such as propylene glycol; aromatic alcohols; polyols containing more than two hydroxyl functions; polyol ethers, alone or as a mixture.

[0178] The organic medium(s), when present, are present in an amount ranging from 0.1% to 40% by weight, preferably from 1% to 30% by weight, or from 3% to 20% by weight, relative to the total weight of the composition according to the invention. pH correction agent

[0179] The composition according to the present invention may comprise (3) at least one pH correcting agent (pH corrector). Two or more pH correcting agents can be used in combination. Thus, a single type of pH correction agent or a combination of different types of pH correction agents can be used.

[0180] As (3) pH correction agent, at least one acidifying agent and / or at least one basifying agent (alkaline agent) may be used.

[0181] The acidifying agent may be a monovalent or polyvalent acid, such as divalent.

[0182] The acidifying agents may be, for example, mineral (inorganic) acids such as hydrochloric acid, sulfuric acid, phosphoric acid, or organic acids such as carboxylic acids, for example tartaric acid, citric acid, lactic acid, as well as sulfonic acids.

[0183] The basifying agent may be a monovalent or polyvalent base, such as divalent.

[0184] Basifying agents can be mineral (inorganic) or organic, or hybrid.

[0185] The mineral basifying agents may be chosen from aqueous ammonia; alkali metal carbonates or bicarbonates such as sodium or potassium carbonates and sodium or potassium bicarbonates; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; and mixtures thereof.

[0186] The organic basifying agents may be chosen from organic amines whose pKb at 25°C is less than 12, preferably less than 10, and even more advantageously less than 6. It should be noted that this is the pKb corresponding to the function of greatest basicity. In addition, the organic amines do not comprise any alkyl or alkenyl fatty chain comprising more than ten carbon atoms.

[0187] The organic basifying agent may be chosen, for example, from alkanolamines, oxyethylenated and / or oxypropylenated ethylenediamines, amino acids and amine compounds of formula (III) below:

[0188] in which

[0189] W represents a divalent C1-C6 alkylene radical optionally substituted by one or more hydroxyl groups or a C1-C6 alkyl radical, and optionally interrupted by one or more heteroatoms such as O and N, and

[0190] Rx, Ry, Rz, and Rt, which may be the same or different, represent a hydrogen atom or a C1-C6 alkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl radical.

[0191] Examples of amine compounds of formula (III) which may be mentioned include 1,3-diaminopropane, 1,3-diamino-2-propanol, spermine and spermidine.

[0192] The term "alkanolamine" designates an organic amine comprising a primary, secondary or tertiary amine function, and one or more linear or branched CrC8 alkyl groups carrying one or more hydroxyl radicals.

[0193] Alkanolamines such as monoalkanolamines, dialkanolamines or trialkanolamines comprising one to three identical or different C1-C4 hydroxyalkyl radicals may be suitable for the present invention. Among the compounds of this type, mention may be made of monoethanolamine (MEA), diethanolamine, triethanolamine, monoisopropa-nolamine, diisopropanolamine, N-dimethylaminoethanolamine, 2-amino-2-methyl-1-propanol, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 3-amino-1,2-propanediol, 3-dimethylamino-1,2-propanediol and tris(hydroxymethylamino)methane.

[0194] The amino acids which can be used are of natural or synthetic origin, in their L, D or racemic form, and comprise at least one acid function chosen more particularly from the carboxylic acid, sulfonic acid, phosphonic acid or phosphoric acid functions. The amino acids can be in neutral or ionic form.

[0195] As amino acids that can be used in the present invention, mention may be made in particular of aspartic acid, glutamic acid, alanine, arginine, omithine, citrulline, asparagine, carnitine, cysteine, glutamine, glycine, histidine, lysine, isoleucine, leucine, methionine, N-phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine.

[0196] It may be preferable that the amino acids are basic amino acids comprising an additional amine function optionally included in a ring or in a ureido function.

[0197] Such basic amino acids may preferably be chosen from those corresponding to formula (IV) below: (IV) R—CH, —CH\ v CO2h

[0198] in which

[0199] R represents a group chosen from:

[0200] -(CH2)3-NH2,

[0201] -(CH2)2-NH2,

[0202] -(CH2)2-NH-CO-NH2, and

[0203] Compounds corresponding to formula (IV) include histidine, lysine, arginine, ornithine and citrulline.

[0204] The organic basifying agent may be chosen from organic amines of heterocyclic type. In addition to histidine which has already been mentioned in the amino acids, mention may in particular be made of pyridine, piperidine, imidazole, triazole, tetrazole and benzimidazole.

[0205] The organic basifying agent may also be chosen from amino acid dipeptides. As amino acid dipeptides which may be used in the present invention, mention may in particular be made of carnosine, anserine and balein.

[0206] The organic basifying agent may also be chosen from compounds comprising a guanidine function. As amines of this type which may be used in the present invention, in addition to arginine, which has already been mentioned as an amino acid, mention may in particular be made of creatine, creatinine, 1,1-dimethylguanidine, 1,1-diethylguanidine, glycocyamine, metformin, agmatine, N-amidinoalanine, 3-guanidinopropionic acid, 4-guanidinobutyric acid and 2-([amino(imino)methyl]amino)ethane-1-sulfonic acid.

[0207] In a preferred embodiment of the present invention, the organic basifying agent may be chosen from amino acids, preferably basic amino acids, and more preferably arginine, lysine, histidine or mixtures thereof. Even more preferably, the organic basifying agent may be arginine.

[0208] Hybrid compounds that may be mentioned include salts of the aforementioned amines with acids such as carbonic acid or hydrochloric acid. Guanidine carbonate or monoethanolamine hydrochloride may in particular be used.

[0209] The (3) pH correcting agent may be present in an amount of 0.01% by weight or more, preferably 0.05% by weight or more, and more preferably 0.1% by weight or more, relative to the total weight of the composition.

[0210] The (3) pH correction agent may be present in an amount of 15% by weight or less, preferably 10% by weight or less, and more preferably 5% by weight or less, relative to the total weight of the composition.

[0211] The (3) pH correction agent may be present in an amount ranging from 0.01% to 15% by weight, preferably from 0.05% to 10% by weight, and more preferably from 0.1% to 5% by weight or less, based on the total weight of the composition.

[0212] It is preferable that the composition according to the present invention has a pH of 4.5 or more, and more preferably of 5 or more.

[0213] It is preferable that the composition according to the present invention has a pH of 6.5 or less, and more preferably 6 or less.

[0214] It is preferable that the composition according to the present invention has a pH of 4.5 to 6.5, and more preferably of 5 to 6.

[0215] The pH of the composition means the pH of the aqueous phase of the composition according to the present invention.

[0216] It may be preferable that at least one buffer or buffering agent is also used, as (3) pH correcting agent, in combination with the acidifying agent and / or the basifying agent, in order to stabilize the pH of the composition according to the present invention.

[0217] As a buffer, any of the commonly known buffers may be used. For example, salts of acids or bases, preferably salts of weak acids or weak bases, may be used. For example, sodium citrate or sodium lactate may be used as a buffer, if citric acid or lactic acid is used as the acidifying agent. Adjuvants

[0218] In a known manner, the composition of the present invention may also contain adjuvants which are customary in the cosmetic, pharmaceutical and / or dermatological field depending on the end uses and / or the specific forms of the products, such as hydrophilic or lipophilic gelling agents, emulsifiers, hydrophilic or lipophilic active agents, preservatives, perfumes, fillers, pH correctors, odor absorbers and dyes. The amounts of these different adjuvants are those conventionally used in the field considered, and for example from 0.01 to 20% by weight of the total weight of the composition.

[0219] These adjuvants and their concentrations must be such that they do not modify the property sought for the composition of the invention.

[0220] The composition according to the invention is preferably in the form of an aqueous gel.

[0221] In a preferred embodiment according to the invention, the composition comprises hydrophilic gelling agents.

[0222] The compositions according to the invention can be manufactured by known processes, generally used in the cosmetic or dermatological field.

[0223] The composition according to the invention finds its application in a large number of cosmetic treatments of keratinous materials such as the skin, the scalp or the mucous membranes (lips), and more particularly the skin, in particular in skin care, to lighten the skin.

[0224] The subject of the invention is also a cosmetic process for caring for or making up keratinous materials, comprising the application to the keratinous materials of a composition as defined above. The subject of the invention is also a non-therapeutic cosmetic process for depigmenting, lightening and / or bleaching keratinous materials, preferably the skin, comprising the step of applying a composition as defined above to the keratinous materials.

[0225] The subject of the invention is also a non-therapeutic cosmetic process for caring for or making up keratinous materials, comprising the application to the keratinous materials of a composition as defined above.

[0226] The invention also relates to the cosmetic use of a composition as defined above, for the care or makeup of keratinous materials.

[0227] More particularly, the subject of the invention is the cosmetic use of a composition as defined above, for skin care, preferably for lightening the skin, and / or reducing or lightening darker and / or more colored spots on the skin.

[0228] In a particular embodiment, the composition is suitable for the treatment of darker and / or more colored spots on the skin. EXAMPLES

[0229] The following examples of compositions according to the invention are given by way of illustration and without limitation. The compounds are indicated by chemical name or INCI name.

[0230] The quantities / concentrations of the ingredients in the compositions / formulas described below are expressed in % by weight, relative to the total weight of each composition / formula, unless otherwise indicated.

[0231] The main raw materials used, their trade names and their suppliers are indicated below. INCI name Trade name Supplier PEG-40 STEARATE TEGO ACID S40 P EVONIK GOLDSCHMIDT SUCROSE TRISTEARATE SURFHOPE SE COSME C-1803 MITSUBISHI-KAGAKU FOODS TRANEXAMIC ACID SPECWHITE® TA SPECCHEM INDUSTRY NIACINAMIDE NIACINAMIDE PC DSM NUTRITIONAL PRODUCTS OLEIC ACID KORTACID 1811 PACIFIC OLEO- CHEMICALS OLEYL ALCOHOL HD-OCENOL® 80 / 85 V BASF ISOSTEARIC ACID PRISORINE™ 3505-LQ-(GD) CRODA HEXYLDECANOL ISOFOL 16 SASOL LAURYL ALCOHOL / MYRISTYL ALCOHOL / CETYL ALCOHOL VEGAROL® 1216 WF ETHYL OLEATE DUB OE HP STEARINERIE DUBOIS ETHYL LINOLEATE VITAMIN F(EE) OLEON PROPYLENE GLYCOL PROPYLENE GLYCOL USP / EP DOW GLYCERIN GLYCERINE 4861 OLEON

[0232] Compound 20 is synthesized as indicated in Example 2 of patent EP3 390 363. Example A

[0233] The inventive compositions of Ex. 1-9, as well as the comparative composition of EC.1-2, were prepared from the ingredients indicated in Table 1 below (in which the contents are indicated in % by weight of materials relative to the total weight of the composition):

[0234] [Tables 1] Components Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7 Ex. 8 Ex. 9 CE. 1 CE. 2 PEG-40 STEARATE 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 GLYCERYL STEARATE 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 PROPYLENE GLYCOL 20 20 20 20 20 20 20 20 20 20 20 ETHYL OLEATE 3 3 3 3 HEXYLDECANOL 3 3 3 3 OLEYL ALCOHOL 5 3 2 LAURYL ALCOHOL / MYRIS TYL ALCOHOL / CETYL ALCOHOL 3 TRANEXAMIC ACID 1 1 1 1 1 1 1 1 1 NIACINAMIDE 4 4 4 4 4 4 COMPOUND 20 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 WATER Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100 Qs per 100

[0235] The compositions were prepared according to the following steps, taking Ex.1 as an example:

[0236] 1). Heat the fatty compounds to 75°C, and mix well until all the solid has melted.

[0237] 2). Mix the soluble raw materials, and heat to 75°C, mix well until there are no lumps.

[0238] 3). Transfer the oily phase into the aqueous phase at 75°C, mixing evenly for 15 min.

[0239] 4). Cool to 30°C.

[0240] 5). Finally, add compound 20 and correct the pH to 5.6 ±0.3. Example B

[0241] The inventive compositions of Ex. 1-9, as well as the comparative composition of CE. 1-2, prepared in Example A were evaluated by Raman spectroscopy and bioavailability study. Raman spectroscopy:

[0242] A LabRam HR Evolution confocal Raman microscope (Horiba Jobin-Yvon, Villeneuve-d'Ascq, France) was used. The Raman spectrum was obtained using a 532 nm DPSS laser with a power of 8 mW on the sample, coupled to a x50 LM Plan objective (Olympus, AN 0.75, Rungis, France). The confocal pinhole was set at 1 00um in diameter for all measurements. The system was spectrally calibrated to the 520.7 cm1 spectral line of silicon before testing. Detection was facilitated by scattering the Raman-shifted radiation onto a charge-coupled device (CCD) detector using a 600-line / mm grating.

[0243] For pure active ingredients, single-point spectra were acquired with a laser intensity of 25% and an acquisition time of 10 seconds, for the spectral range 400 - 2000 cm A

[0244] For formula trial mapping, the step size was 3 pm in the X and Y directions. The acquisition areas were 18 X 150 pm. For each spot, a laser intensity of 50% and an acquisition time of 5 seconds per spectrum were used. The spectral range was from 400 to 2000cm1.

[0245] For the test, skin tissue samples were prepared as follows: for sample preparation, 6 µL of formula was applied evenly to a 0.8 cm X 0.8 cm porcine skin, corresponding to 9 mg / cm2. The porcine skin sample was then emerged onto an insert membrane with PBS underneath, followed by incubation at 37°C at 95% relative humidity for 6 hours. The treated sample was embedded in OCT, then frozen and cryo-sectioned into 20 µm thickness. It was then placed on a CaF2 substrate for confocal Raman scanning. Three porcine samples were prepared for each formula. A confocal Raman map was acquired for each treated sample. Bioavailability study:

[0246] For the percutaneous absorption study, vertical diffusion cells were used. The study was conducted using the following procedure: the formula containing the active ingredient of interest was applied to skin samples (n=9) at 5 mg / cm2. After 16 hours of exposure, the unabsorbed residues remaining on the skin surface were removed by washing, the stratum corneum was then collected by removal with adhesive tape (20 passes, grouped by 10), the epidermis, the dermis and the receptor fluid were collected. The active ingredients were extracted from each of the collected compartments: washing, removal with adhesive tape, epidermis, dermis and receptor fluid, and the quantity of active ingredients was quantified by LC MS / MS. The mass balance was checked to see if the amount of T applied to the skin was recovered at the end of the experiment; data were excluded when the mass balance did not meet the criterion of 100 ± 15%.

[0247] [Table 2] Table 2 Data on active delivery in the bioavailability test - corresponding to Table 1 Properties Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7 Ex. 8 Ex. 9 EC. 1 EC. 2 Raman (compound 20) VVVVVAAX Raman (TXA) AAOAX Bioavailability (compound 20) 3.15% 1.48% Bioavailability (TXA) 2.3% 2.3% 0.11%

[0248] V: The signal can be observed in the stratum corneum, epidermis; A: A scattered signal can be found in the epidermis;

[0249] O: a weak signal can be found in the epidermis; and

[0250] x: no signal can be observed in the skin

[0251] The results are also provided in Figures 1 and 2. For compound 20, signals were observed in the stratum corneum and epidermis in Ex.1, Ex.4, Ex.5, Ex.6, Ex.7, Ex.8 and Ex.9 while no signals were found in EC.2. For active TXA, weak or scattered signals were found in the epidermis in Ex.2, Ex.4, Ex.6 and Ex.7 while no signals were found in EC.1.

[0252] [Table 3] Table 3: Bioavailability data: Formulation Ex. 1 Ex. 2 Ex. 3 EC. 2 EC. 1 N=7, % of applied dose (mean ± standard deviation) Stratum corneum 6.36+1.99 7.80+1.50 9.80+1.90 2.61+1.36 0.21+0.08 Epidermis 2.41+1.53 1.30+1.60 1.10+0.90 0.87+0.49 0.048+0.042 Dermis 0.25+0.21 0.66+0.66 0.44+0.25 0.29+0.23 0.018+0.011 Receptor fluid (RF) 0.49+0.74 0.077+0.104 0.13+0.13 0.31+0.38 0.015+0.016 Epidermis+Dermis+F 3.15+2.08 2.30+2.30 2.30+2.30 1.48+0.73 0.11+0.06 R

[0253] The bioavailability results were shown in Tab.3. For the inventive examples, high % of applied dose in the skin in the sample formulas, notably more than 1% of active in (Epidermis+dermis+FR) were obtained; while less active was found in the skin in EC. 1 and EC.2. Example C

[0254] The inventive compositions of Ex. 10-11, as well as the comparative composition of EC.3, were prepared from the ingredients indicated in Table 2 below (in which the contents are indicated in % by weight of materials relative to the total weight of the composition):

[0255] [Table 4] Table 4 Components Ex. 10 Ex. 11 EC. 3 PEG-40 STEARATE 1,2 1,2 1,2 SUCROSE TRISTEARATE 0,5 0,5 0,5 GLYCERIN 9 9 9 ETHYL OLEATE 1 HEXYLDECANOL 1 ETHYL LINOLEATE 3 TRANEXAMIC ACID 1 1 1 NIACINAMIDE 4 4 4 COMPOUND 20 0,5 0,5 0,5 WATER Qs per 100 Qs per 100 Qs per 100 Example D

[0256] The inventive compositions of Ex. 10-11, as well as the comparative composition of EC.3, prepared in Example C were evaluated by Raman spectroscopy as set forth in Example B.

[0257] The result was shown in [Fig.3]. The three formulas are comparable in signal intensity and depth of compound 20 in pig skin, all signals can be observed in the stratum corneum, epidermis and dermis.

[0258] The result has also been shown in [Fig.4]. For Ex.10, the TXA signal is uniformly distributed in the stratum corneum, epidermis and dermis. But for Ex. 11 & EC.3, no obvious signal can be observed in the epidermis, only in the stratum corneum and dermis.

[0259] It is concluded that with the technical solutions of the present invention, using a fatty compound having at most one C=C bond, the formulas can achieve a penetration of the active substance comparable to that of conventional formulas having 2 or more C=C bonds, but inhibit or even avoid the storage instability defect brought about by the more numerous C=C bonds.

Claims

1. Claims Composition comprising the following components: A) at least one compound chosen from the compounds of formula (I) and the tautomer of formula (I1) below; and their salts, optical isomers, racemates, and / or solvates such as hydrates, alone or as a mixture: O (I) of) formulas (I) and (I') in which: -Ri denotes a radical chosen from: a) a hydrogen atom; b) a linear (C1-C10) or branched (C3-C10) alkyl group, in particular a linear (C1-C6) or branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl; in particular said alkyl group of R1 is not substituted;- R2 denotes a radical chosen from: a) a hydrogen atom; (b) a linear or branched C1-C12 or cyclic C3-C12 saturated hydrocarbon group, optionally substituted by one or more groups, which may be the same or different, chosen from: (i) -O-R3 ii) -S-R3 iii) -C(O)-O-R3; iv) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals c) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C8 alkoxy radicals -R3 denotes a radical chosen from: a) a hydrogen atom; b) a saturated linear C1-C10 or branched C3-C10 alkyl group; B) at least one C12-20 fatty compound, preferably a compound C12-C18 fatty acid, or preferably a C12-C16 fatty compound, having at most one C=C bond, provided that when component B) is a fatty acid, it is a C12-C16 fatty acid.

2. Composition according to any one of the preceding claims, in which: -R2 of formula (I) and (F) represents a hydrogen atom, or -R2 of formula (I) and (F) represents a linear (C1-C10) or branched (C3-C10) alkyl group, in particular a linear (C1-C6) or branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R2 being unsubstituted.

3. Composition according to any one of the preceding claims, in which: -R3 of formula (I) and (F) represents a hydrogen atom; or -R3 of formula (I) and (F) represents a linear C1-C10 or branched C3-C10 saturated alkyl group; in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group such as the methyl group.

4. Composition according to any one of the preceding claims, in which: -Ri of formula (I) and (F) represents a radical chosen from: a) a hydrogen atom; b) a linear saturated C1-C6 or C3-C6 branched alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from: i) -O-R3 ii) -S-R3; preferably optionally substituted by one or more groups i) -R2 of formula (I) and (F) represents a radical chosen from: a) a hydrogen atom; b) a linear saturated C1-C10 or branched C3-C10 or cyclic C3-C8 as well as C5-C6 hydrocarbon group, optionally substituted by one or more groups, which may be the same or different, chosen from: i) -O-R3 ii) -SR-, iii) -C(O)-O-R3; iv) a phenyl group optionally substituted by one or more hydroxyls and / or by one or more C1-C4 alkoxy radicals such as methoxy; preferably substituted by one or more groups chosen from i) and iii), preferentially iii) such as carboxy -R3 of formula (I) and (I1) represents a radical chosen from: a) a hydrogen atom; b) a linear C1-C6 or branched C3-C6 saturated alkyl group; preferably, the compounds of formula (I) and the tautomer (I1) or their salts, their optical isomers, racemates, and / or solvates such as hydrates and their derivatives, alone or as a mixture; have the following meanings: -Ri of formula (I) and (I1) represents a radical chosen from: a) a hydrogen atom; b) a linear C1-C4 or branched C3-C4 saturated alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from i) -OR3jplus preferably unsubstituted; -R2 of formula (I) and (!') represents a radical chosen from: a) a hydrogen atom; (b) a linear C1-C10 or branched C3-C10 or cyclic C3-C8 or C5-C6 saturated hydrocarbon group, optionally substituted by one or more groups, which may be the same or different, chosen from: i) -O-R3 iii) -C(O)-O-R3; iv) a C5-C12 aryl group, optionally substituted by one or more hydroxyls and / or by one or more C1-C4 alkoxy radicals -R3 of formula (I) and (!') represents a radical chosen from: a) a hydrogen atom; (b) a linear C1-C4 or branched C3-C4 saturated alkyl group such as methyl or ethyl.

5. A composition according to any preceding claim, wherein: the compound of formula (I) selected from the group consisting of compounds 1 to 24 below and their tautomer or their salts, their optical isomers, their racemates and / or their solvates such as hydrates, alone or as a mixture, in particular compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20 or 21, more particularly 1, 9, 16, 18, 19, 20 or 21, preferably 18, 19, 20 or 21, more preferably 20: No. Structure Chemical Name 1 h ' ih X -À-VH N-ethyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 2 N-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 3 N-octyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 4 h ? c tj N-benzyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 5 ç' / ■—'SS '— N-phenyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 6 0 > Z'" 'sZ H 1 HH ' N-cyclohexyl-2-thioxo-1,2-dihydropyridine -3-carboxamide 7 L !.. N- [2- (4-methoxyphenyl)ethyl 1 ] -2-thioxo-1,2-dihydropyridine-3-carboxamide 8 As ,^v ..Av V$Z' '^l*' ''•••'•' Z<>x Z 0 N-(2-methylpropyl)-2-thioxo-1,2-dihydropyridine-3-carboxamide de 9 ï h N-pentyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 10 A * ... , - . Y r ■■ ' ' N-nonyl-2-thioxo-1,2-dihydropyridine-3-carboxamide 11 zX z^xh ¢. Z. "■....... H N-(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxami of 12 G â l N,N-diéthyl 2-mercaptonicotinamide 13 ç fl J K -b- b ^"’-'^-OH If \k. N-éthyl-N-(2-hydroxyéthyl)-2 -thioxo-1,2-dihydropyridine-3-carboxami de 14 •fjfz x^x x N-(2,3-dihydroxypropyl)-2-th ioxo-1,2- dihydropyridine-3-carboxami de 15 ■ ■ AX. ■■ xA\.. N- ( 1,3 -dihy droxypropan-2- y 1) -2-thioxo-1,2-dihydropyridine -3-carboxamide 16 f y y 'Vf,.'- X^:; / Éthyl N- [(2-thioxo-1,2-dihydropyridin -3-yl) carbonyl] alaninate 17 çCY Éthyl N- [(2-thioxo-1,2-dihydropyridin -3-yl) carbonyl]phényl alaninate 18 X XXy' V^X h r i. ï X b * i " 1 Éthyl N-méthyl-N-[(2-thioxo-1,2-dihy dropyridin -3-yl)carbonyl]glycinate 19 jl ;- > <s éthyl n- [(2-thioxo-1,2-dihydropyridin -3-yl) carbonyl]glycinate 20 jl, l. jxx $ [(2-thioxo-1,2-dihydropyri din-3-yl) carbonyl] glycine 21 ;-x u -x 'm''’ xs h n-méthyl-n- [(2-thioxo-1,2-di hydropyridin -3-yl)carbonyl]glycine 22 j'^. xx>*x ><' x" N,N-bis(2-hydroxyethyl)-2-thioxo-1,2-dihydropyridine-3-carboxami de 23 J'x .--"^x. z*x \ N-(3-methoxypropyl)-2-thiox ol,2- dihydropyridine-3-carboxami de 24 A' L N-butyl-2-thioxo-1,2-dihydro pyridine-3-carboxamide

6.

7.

8. A composition according to any preceding claim, wherein component A) is selected from those having a log P in the range -1.6 to 0.

5. A composition according to any one of the preceding claims, wherein an additional hydrophilic active compound having a log P of -1.6 to 0.5 is used as component A') in combination with component A), component A') being preferably selected from the group consisting of water-soluble vitamins, cosmetically acceptable derivatives of niacinamide, and tranexamic acid, preferably ascorbic acid, niacinamide or tranexamic acid. A non-therapeutic cosmetic method for depigmenting, lightening and / or bleaching keratin materials, preferably the skin, comprising the step of applying a composition according to one of claims 1 to 8 to the keratin materials.< / s>

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