Solubilization of Thiopyridinone Compounds and Compositions Containing Thiopyridinone Compounds

Abstract

The present invention relates to a composition comprising (1) at least one thiopyridinone compound and (2) at least one compound selected from vitamin B3 and its derivatives. The present invention can provide a composition containing (1) a thiopyridinone compound, in which the solubility of the thiopyridinone compound over time is enhanced.

Description

Technical Field

[0001] The present invention relates to a stabilized composition containing a thiopyridinone compound and its use for caring for keratinous substances, in particular the skin.

Background Art

[0002] At various times in life, some people have darker and / or more pigmented spots on their skin, more particularly on the appearance of the face and hands, giving the skin an inhomogeneity. These spots are due in particular to a high concentration of melanin in the keratinocytes located on the surface of the skin.

[0003] For the purpose of treating pigmented spots, the use of substances that are effective and harmless for local depigmentation is most specifically desired.

[0004] For example, arbutin, niacinamide and kojic acid are known as skin depigmenting agents.

[0005] On the other hand, it has been discovered that certain thiopyridinone compounds, such as those disclosed in WO2012 / 080075 and WO2017 / 102349, exhibit good depigmenting action even at low concentrations. Thiopyridinone compounds can exhibit a strong depigmenting or whitening effect by reducing the production of melanin.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0007] However, it has been found that the thiopyridinone compound may be incompletely solubilized in the composition, whereby the bioavailability of the thiopyridinone compound may be reduced. Therefore, there is a need for a composition containing a thiopyridinone compound with enhanced solubility and stability over time.

Means for Solving the Problems

[0008] The above object is (1) A compound of the following formula (I), a tautomer of the following formula (I')

[0009]

Chemical Formula

[0010] (In the formula, R1 is a) a hydrogen atom, and b) one or more groups selected from the following, which may be the same or different: i) -O-R3 and ii) -S-R3 optionally substituted with one or more groups selected from a saturated straight-chain C1-C 10 or branched C3-C 10 alkyl group represents a group selected from, R2 is a) a hydrogen atom, b) one or more groups selected from the following, which may be the same or different: i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) a C5-C 12 aryl group optionally substituted with one or more hydroxyls and / or one or more C1-C8 alkoxy groups optionally substituted with one or more groups selected from a saturated straight-chain C1-C 12 or branched C3-C 12 or cyclic C3-C8 hydrocarbon group, and c) A C5-C aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 aryl group selected from the group consisting of), R3 is a) a hydrogen atom, and b) a saturated straight-chain C1-C 10 or branched C3-C 10 alkyl group selected from the group consisting of), at least one compound selected from these salts, solvates such as hydrates of these, optical isomers of these, racemates of these, and mixtures of these, and (2) at least one compound selected from vitamin B3 and its derivatives can be achieved by a composition containing

[0011] Preferably R1 in formulas (I) and (I') represents a hydrogen atom, or or R1 in formulas (I) and (I') is a straight-chain (C1-C 10 ) alkyl group or a branched (C3-C 10 ) alkyl group, particularly a straight-chain (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably represents ethyl, and in particular the alkyl group of R1 is unsubstituted.

[0012] Preferably R2 in formulas (I) and (I') represents a hydrogen atom, or or R2 in formulas (I) and (I') is a straight-chain (C1-C 10 ) alkyl group or a branched (C3-C 10 ) alkyl group, particularly a straight-chain (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably represents methyl or ethyl group, and the alkyl group of R2 is unsubstituted.

[0013] Preferably, R2 in formulas (I) and (I') is a linear (C1-C 10 ) alkyl group or a branched (C3-C 10 ) alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, and the alkyl group may be substituted with one or more groups selected from i), ii), iii) and iv) as defined above. Preferably, the alkyl group is substituted with one or two groups selected from i), ii) and iii), more preferably with one or two groups selected from i) and iii), and even more preferably with one group iii) as carboxy.

[0014] Preferably, R2 in formulas (I) and (I') represents a (C3-C8) cycloalkyl group, preferably a (C5-C7) cycloalkyl group, such as cyclohexyl, or or R2 in formulas (I) and (I') represents a C5-C 12 aryl group optionally substituted with one or more hydroxyls and / or one or more C1-C8 alkoxy groups, preferably a phenyl group which is particularly unsubstituted.

[0015] Preferably, R3 in formulas (I) and (I') represents a hydrogen atom, or or R3 in formulas (I) and (I') represents a saturated linear C1-C 10 or branched C3-C 10 alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group, such as a methyl group.

[0016] More preferably, R1 in formulas (I) and (I') is a) a hydrogen atom, and b) which may be the same or different i) -O-R3 and ii) -S-R3 (optionally substituted by one or more groups i)) a saturated straight-chain C1-C6 or branched C3-C6 alkyl group optionally substituted by one or more groups selected from groups selected from R2 in formulas (I) and (I') is a) a hydrogen atom, and b) which may be the same or different i) -O-R3, ii) -S-R 3、 iii) -C(O)-O-R3, and iv) a phenyl group optionally substituted by one or more hydroxyls and / or one or more C1-C4 alkoxy groups, such as methoxy one or more groups selected from preferably one or more groups selected from i) and iii), preferably one or more groups substituted by iii) such as carboxy a saturated straight-chain C1-C 10 or branched C3-C 10 or cyclic C3-C8, such as C5-C6 hydrocarbon group groups selected from R3 in formulas (I) and (I') is a) a hydrogen atom, and b) a saturated straight-chain C1-C6 or branched C3-C6 alkyl group and groups selected from Preferably, the compounds of formula (I) and the tautomers (I'), their salts, their solvates such as hydrates, their optical isomers, their racemates, and mixtures thereof have the following meanings: R1 in formulas (I) and (I') is a) a hydrogen atom, and b) A saturated straight-chain C1-C4 or branched C3-C4 alkyl group, optionally substituted with one or more groups selected from -OR3, more preferably unsubstituted, which may be the same or different. represents a group selected from R2 in formulas (I) and (I') is a) a hydrogen atom, and b) one or more groups selected from, which may be the same or different, i) -O-R3, iii) -C(O)-O-R3, and iv) a C5-C aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C4 alkoxy groups 12 aryl group a saturated straight-chain C1-C or branched C3-C 10 or cyclic C3-C8, such as C5-C6 hydrocarbon group, optionally substituted with one or more groups selected from 10 represents a group selected from R3 in formulas (I) and (I') is a) a hydrogen atom, and b) a saturated straight-chain C1-C4 or branched C3-C4 alkyl group, such as methyl or ethyl represents a group selected from The compound can be selected from the following compounds 1-24, their tautomers, their salts, their solvates such as hydrates, their optical isomers, their racemates, and their mixtures, especially compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20 or 21, more specifically 1, 9, 16, 18, 19, 20 or 21, preferably 18, 19, 20 or 21, and more preferably 20.

[0017] (1) The compound can be selected from the following compounds 1-24, their tautomers, their salts, their solvates such as hydrates, their optical isomers, their racemates, and their mixtures, especially compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20 or 21, more specifically 1, 9, 16, 18, 19, 20 or 21, preferably 18, 19, 20 or 21, and more preferably 20.

[0018]

Table 1A

[0019]

Table 1B

[0020]

Table 1C

[0021]

Table 1D

[0022] The amount of the (1) compound in the composition according to the present invention may be 0.01% by mass to 10% by mass, preferably 0.05% by mass to 5% by mass, more preferably 0.1% by mass to 3% by mass, based on the total mass of the composition.

[0023] At least one compound (2) is preferably vitamin B3.

[0024] The amount of vitamin B3 or its derivative in the composition according to the present invention may be 0.06% by mass to 60% by mass, preferably 0.3% by mass to 30% by mass, more preferably 0.6% by mass to 18% by mass, based on the total mass of the composition.

[0025] The composition according to the present invention may be for keratin substances, preferably for skin whitening.

[0026] The present invention also relates to a beauty method, preferably a whitening method, for keratin substances, preferably for skin, which comprises the step of applying the composition according to the present invention to a keratin substance.

[0027] Another aspect of the present invention is (1) a compound of the following formula (I), a tautomer of the following formula (I')

[0028]

Chemical formula

[0029] (wherein, R1 is a) a hydrogen atom, and b) one or more groups selected from i) -O-R3 and ii) -S-R3 optionally substituted with one or more groups selected from saturated linear C1-C 10 or branched C3-C 10 alkyl groups selected from, R2 is a) a hydrogen atom, b) one or more groups selected from i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) C5-C 12 aryl groups optionally substituted with one or more hydroxyls and / or one or more C1-C8 alkoxy groups selected from saturated linear C1-C 12 or branched C3-C 12 or cyclic C3-C8 hydrocarbon groups, and c) groups selected from C5-C 12 aryl groups optionally substituted with one or more hydroxyls and / or one or more C1-C8 alkoxy groups selected from, R3 is a) a hydrogen atom, and b) saturated linear C1-C 10 or branched C3-C 10 alkyl groups selected from), Use of at least one compound selected from (2) vitamins B3 and derivatives thereof in a composition comprising at least one compound selected from these salts, solvates such as hydrates thereof, these optical isomers, these racemates, and mixtures thereof, (1) for stabilizing the compound.

Best Mode for Carrying Out the Invention

[0030] As a result of intensive studies, the present inventors have discovered that it is possible to provide a composition containing a thiopyridinone compound or a thiopyridinone compound in which the solubility of the thiopyridinone compound over time is enhanced.

[0031] Therefore, the composition according to the present invention is (1) A compound of the following formula (I), a tautomer of the following formula (I'),

[0032]

Chemical formula

[0033] (In the formula, R1 is a) a hydrogen atom, and b) one or more groups selected from the group consisting of i) -O-R3 and ii) -S-R3, optionally substituted by one or more groups selected from saturated linear C1-C 10 or branched C3-C 10 alkyl group selected from the group consisting of, R2 is a) a hydrogen atom, b) one or more groups selected from the group consisting of i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) C5-C 12 aryl group optionally substituted by one or more hydroxyls and / or one or more C1-C8 alkoxy groups selected from the group consisting of, 12 or branched C3-C 12 or cyclic C3-C8 hydrocarbon group, and c) A C5-C aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 aryl group selected from the groups shown, R3 is, a) a hydrogen atom, and b) a saturated straight-chain C1-C 10 or branched C3-C 10 alkyl group selected from the groups shown), at least one compound selected from these salts, solvates such as hydrates thereof, these optical isomers, these racemates, and mixtures thereof (hereinafter, the compound is referred to as "thiopyridinone compound"), and (2) at least one compound selected from vitamin B3 and derivatives thereof and contains.

[0034] The composition according to the present invention can exhibit enhanced solubility of the (1) thiopyridinone compound contained therein.

[0035] In other words, the composition according to the present invention can enhance the solubility of the (1) thiopyridinone compound therein. The enhanced "solubility" means that the composition according to the present invention containing the (1) thiopyridinone compound shows no turbidity, but rather is uniform, transparent, and stable.

[0036] In addition, the enhanced solubility of the (1) thiopyridinone compound can lead to improved or enhanced bioavailability of the (1) thiopyridinone compound that can function as a decolorizing agent or whitening agent. Therefore, the composition according to the present invention can bring about an enhanced or improved decolorizing or whitening effect.

[0037] Hereinafter, the composition, use, etc. according to the present invention will be described in detail.

[0038] [Composition] The composition according to the present invention is (1) At least one thiopyridinone compound, and (2) at least one compound selected from vitamin B3 and its derivatives is included.

[0039] (1) The thiopyridinone compound, and (2) vitamin B3 and its derivatives, and other features of the composition according to the present invention will be described below.

[0040] (Thiopyridinone compound) The composition according to the present invention includes (1) at least one thiopyridinone compound. Two or more (1) thiopyridinone compounds may be used in combination. Therefore, a single type of (1) thiopyridinone compound, or a combination of different types of (1) thiopyridinone compounds can be used.

[0041] (1) The thiopyridinone compound is a compound of the following formula (I), a tautomer of the following formula (I'),

[0042]

Chemical formula

[0043] (In the formula, R1 is a) a hydrogen atom, and b) one or more groups selected from i) -O-R3 and ii) -S-R3 optionally substituted by one or more groups selected from saturated linear C1-C 10 or branched C3-C 10 alkyl group is shown, R2 is a) a hydrogen atom, b) one or more groups selected from i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) a C5-C aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 aryl group A saturated straight-chain C1-C or branched C3-C 12 or branched C3-C 12 or cyclic C3-C8 hydrocarbon group, and c) A C5-C aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 aryl group selected from the group consisting of, R3 is a) a hydrogen atom, and b) a saturated straight-chain C1-C or branched C3-C 10 or branched C3-C 10 alkyl group selected from the group consisting of), Selected from these salts, solvates such as their hydrates, these optical isomers, these racemates, and mixtures thereof.

[0044] For the purposes of the present invention, unless otherwise specified, it is as follows. - "Saturated straight-chain C1-C or branched C3-C 12 or branched C3-C 12 " The hydrocarbon group is a saturated straight-chain C1-C or branched C3-C 12 or branched C3-C 12 hydrocarbon-based group, preferably a straight-chain C1-C or branched C3-C 10 or branched C3-C 10 hydrocarbon-based group, more preferably a straight-chain C1-C6 or branched C3-C6 hydrocarbon-based group corresponding to "linear (C1-C 12 ) alkyl or branched (C3-C 12) is equivalent to an "alkyl group". Preferably, the linear or branched group can be selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl. More preferably, the saturated linear or branched alkyl group can be selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl and octyl, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl. - The saturated "cyclic C3-C8" hydrocarbon group is a monocyclic or bicyclic cycloalkyl group containing 3 to 8 carbon atoms, particularly a C5-C7 monocyclic cycloalkyl group such as a cyclohexyl group. - The "alkoxy group" is an alkyloxy group in which the alkyl group is a linear or branched C1-C 16 , preferably a C1-C8 hydrocarbon-based group. - When the alkoxy group is optionally substituted, this implies that the alkyl group is optionally substituted as defined above. - The "aryl" group represents a fused or non-fused monocyclic or bicyclic carbon-based group containing 5 to 12 carbon atoms, preferably 6 to 10 carbon atoms, at least one of the rings being aromatic. Preferably, the aryl group is phenyl, biphenyl, naphthyl, more preferably a phenyl group. - The term "at least one (kind of)" is synonymous with the term "one (kind of) or more". - The term "including both ends" regarding the concentration range means that the upper and lower limits of the range are included within a predetermined range.

[0045] Salts of the compounds of formula (I), (I'), (II), or (II') as defined below include conventional non-toxic salts of said compounds, for example those formed from organic or inorganic acids or from organic or inorganic bases.

[0046] Salts of the compounds of formula (I), (I'), (II), or (II') include A compound of formula (I) or (II) is - added to, for example, an inorganic base such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, and sodium carbonate, potassium carbonate or calcium carbonate or bicarbonate, or - an organic base such as a primary, secondary, or tertiary alkylamine, for example triethylamine or butylamine, to obtain salts. This primary, secondary or tertiary alkylamine may contain one or more nitrogen and / or oxygen atoms and thus may contain, for example, one or more alcohol functional groups. In particular, 2-amino-2-methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol and 3-(dimethylamino)propylamine can be mentioned.

[0047] Also, salts of amino acids such as lysine, arginine, guanidine, glutamic acid and aspartic acid can be mentioned. Advantageously, the salts of the compounds of formula (I) or (II) (when it contains a carboxy group) can be selected from alkali metal salts or alkaline earth metal salts, for example, sodium salts, potassium salts, calcium salts or magnesium salts, and ammonium salts.

[0048] The "organic or inorganic acid salts" are, more specifically, i) hydrochloric acid HCl, ii) hydrobromic acid HBr, iii) sulfuric acid H2SO4, iv) alkylsulfonic acid: Alk-S(O)2OH, such as methanesulfonic acid and ethanesulfonic acid, v) arylsulfonic acid: 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 acid: Alk-O-S(O)OH, such as methoxysulfinic acid and ethoxysulfinic acid, xi) aryloxysulfinic acid, such as tolueneoxysulfinic acid and phenoxysulfinic acid, xii) phosphoric acid H3PO4, xiii) acetic acid CH3C(O)OH, xiv) trifluoromethanesulfonic acid CF3SO3H, and xv) salts derived from tetrafluoroboric acid HBF4, and are selected from the salts so selected.

[0049] Acceptable solvates of the compounds described herein include conventional solvates such as those formed during the preparation of said compounds as a result of the presence of a solvent. For example, solvates resulting from the presence of water, or linear or branched alcohols (such as ethanol or isopropanol) can be mentioned.

[0050] Optical isomers are, in particular, enantiomers and diastereoisomers.

[0051] Compound (I') is the tautomeric form of compound (I) when a tautomeric equilibrium exists according to the following scheme.

[0052]

Chemical formula

[0053] According to one embodiment of the present invention, R1 represents one hydrogen atom.

[0054] According to another embodiment of the present invention, R1 is a linear (C1-C 10 ) alkyl group or a branched (C3-C 10)An alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, is represented. In particular, the alkyl group of R1 is unsubstituted.

[0055] According to one embodiment of the present invention, R2 represents one hydrogen atom.

[0056] According to another embodiment of the present invention, R2 is a linear (C1-C 10 )alkyl group or a branched (C3-C 10 )alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably a methyl or ethyl group, and the alkyl group of R2 is unsubstituted.

[0057] According to another embodiment of the present invention, R2 is a linear (C1-C 10 )alkyl group or a branched (C3-C 10 )alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, and the alkyl group is substituted by one or more groups selected from i), ii), iii) and iv) defined above. Preferably, the alkyl group is substituted by one or two groups selected from i), ii), and iii), more preferably by one or two groups selected from i) and iii), and even more preferably by one group iii) as carboxy.

[0058] Another variant of the group R2 is one in which the alkyl group is substituted by one group iv), particularly by one phenyl group.

[0059] According to another embodiment of the present invention, R2 represents a (C3-C8) cycloalkyl group, preferably a (C5-C7) cycloalkyl group, such as cyclohexyl.

[0060] According to another embodiment of the present invention, R2 is a C5-C 12 aryl group, preferably an unsubstituted phenyl group, optionally substituted with one or more hydroxyls and / or one or more C1-C8 alkoxy groups.

[0061] According to one embodiment, R3 represents a hydrogen atom.

[0062] According to another embodiment, R3 is a saturated straight-chain C1-C 10 or branched C3-C 10 alkyl group, particularly a straight-chain (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group, such as a methyl group.

[0063] Preferably, the compound of formula (I) and the tautomer (I'), or salts thereof, optical isomers, racemates, and / or solvates such as hydrates thereof, either alone or as a mixture, have the following meanings: R1 is a) a hydrogen atom, and b) one or more groups, which may be the same or different, i) -O-R3 and ii) -S-R3 (preferably substituted with one or more groups i)) a saturated straight-chain C1-C6 or branched C3-C6 alkyl group optionally substituted with one or more groups selected from groups selected from R2 is a) a hydrogen atom, and b) one or more groups, which may be the same or different, i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) a phenyl group optionally substituted with one or more hydroxyls and / or one or more C1-C4 alkoxy groups, such as methoxy. One or more groups selected from, Preferably one or more groups selected from i) and iii), preferably one or more groups substituted with iii) such as carboxy, Optionally substituted saturated straight-chain C1-C 10 Or branched C3-C 10 Or cyclic C3-C8, such as C5-C6 hydrocarbon group Indicates a group selected from, R3 is, a) A hydrogen atom, and b) A group selected from saturated straight-chain C1-C6 or branched C3-C6 alkyl groups Indicates a group selected from.

[0064] Preferentially, the compound of formula (I) and the tautomer (I'), or salts thereof, optical isomers, racemates, and / or solvates such as hydrates thereof, alone or as a mixture, Have the following meanings: R1 is, a) A hydrogen atom, as well as b) Optionally substituted, more preferably unsubstituted, saturated straight-chain C1-C4 or branched C3-C4 alkyl groups, with one or more groups selected from i) -OR3, which may be the same or different. Indicates a group selected from. R2 is, a) A hydrogen atom, as well as b) Optionally substituted with one or more groups selected from, which may be the same or different, i) -O-R3, iii) -C(O)-O-R3, iv) C5-C optionally substituted with one or more hydroxyls and / or one or more C1-C4 alkoxy groups 12 Aryl group Optionally substituted with one or more groups selected from saturated straight-chain C1-C 10 Or branched C3-C 10 Or cyclic C3-C8, such as C5-C6 hydrocarbon group Indicates a group selected from. R3 represents a) a hydrogen atom, and b) a saturated straight-chain C1-C4 or branched C3-C4 alkyl group, such as methyl or ethyl and represents a group selected from these.

[0065] Preferably, the compound of formula (I) and the tautomer (I'), or salts thereof, these optical isomers, racemates, and / or solvates such as hydrates thereof, alone or as a mixture, are having the following meanings: R1 is a hydrogen atom, R2 is a) a hydrogen atom, and b) one or more groups selected from v)-C(O)-O-R3, which may be the same or different, preferably substituted with one group iii)-C(O)-O-R3, and represents a group selected from saturated straight-chain C1-C5 or branched C3-C5 or cyclic C3-C8, such as C5-C6 hydrocarbon groups, and R2 is more preferably a saturated straight-chain C1-C4 or branched C3-C4 hydrocarbon group substituted with one group iii)-C(O)-OR3, R3 is a) a hydrogen atom, and b) a saturated straight-chain C1-C4 or branched C3-C4 alkyl group, such as methyl or ethyl and represents a group selected from these.

[0066] According to another preferred embodiment, the compound of formula (I) and the tautomer (I') are selected from the following compound of formula (II), further the tautomer of the following formula (II'), salts thereof, solvates thereof, and optical isomers thereof, and racemates thereof, alone or as a mixture.

[0067] [Table 2]

[0068] R1 and R3 in formulas (II) and (II') have the same meanings as R1 and R3 in the compounds of formulas (I) and (I'), and X is an alkylene group -(CH2) n -(wherein n is an integer in the range including both ends from 1 to 10, preferably in the range from 1 to 6, more preferably in the range from 1 to 4, for example, 1), and preferably, R3 represents a hydrogen atom.

[0069] Among the compounds of formula (I), the following compounds and their tautomers, or salts thereof, these optical isomers, racemates, and / or solvates such as their hydrates, etc., are preferably used either alone or as a mixture.

[0070]

Table 3A

[0071]

Table 3B

[0072]

Table 3C

[0073]

Table 3D

[0074] Among these compounds, the following compounds are more specifically preferred.

[0075]

Table 4A

[0076]

Table 4B

[0077]

Table 4C

[0078] More preferably, among these compounds, the following compounds are more specifically preferred.

[0079] [Table 5]

[0080] Even more preferably, among these compounds, the following compounds are more specifically preferred.

[0081] [Table 6]

[0082] In the most preferred embodiment, the compound according to the present invention is as follows.

[0083] [Table 7]

[0084] All of the above compounds can be obtained from commercially available reagents by chemical methods known to those skilled in the art.

[0085] (1) The thiopyridinone compound can be prepared, for example, according to the method described in EP-A-3390363 or WO2017 / 102349, which is incorporated herein by reference.

[0086] (1) Thiopyridinone compounds may be active ingredients or active compounds in cosmetics or dermatological products. As used herein, the term "active" ingredient or compound means an ingredient or compound having cosmetic or dermatological active properties such as antioxidant effect, whitening effect, UV shielding effect, and antibacterial effect. The (1) thiopyridinone compounds used in the present invention can function as a depigmenting agent, a bleaching agent or a whitening agent, and thus the compositions according to the present invention can be used as whitening products or as cosmetic compositions for whitening keratinous substances.

[0087] (1) Thiopyridinone compounds can be used as agents for decolorizing, bleaching or whitening the skin, hair, eyelashes or hair, and further the lips and / or nails, preferably the skin, particularly for removing pigmented spots or senescence spots and / or as a sunscreen agent.

[0088] The amount of the (1) thiopyridinone compound in the composition according to the present invention may be 0.01% by mass or more, preferably 0.05% by mass or more, more preferably 0.1% by mass or more, based on the total mass of the composition.

[0089] On the other hand, the amount of the (1) thiopyridinone compound in the composition according to the present invention may be 10% by mass or less, preferably 5% by mass or less, more preferably 3% by mass or less, based on the total mass of the composition.

[0090] The amount of the (1) thiopyridinone compound in the composition according to the present invention may be in the range of 0.01% by mass to 10% by mass, preferably 0.05% by mass to 5% by mass, more preferably 0.1% by mass to 3% by mass, based on the total mass of the composition.

[0091] (Vitamin B3) Vitamin B3, also called vitamin PP, has the following formula:

[0092] [Chemical formula]

[0093] [wherein, R may be -CONH2 (niacinamide), -COOH (nicotinic acid or niacin), or CH2OH (nicotinyl alcohol), -CO-NH-CH2-COOH (nicotinuric acid), or -CO-NH-OH (nicotinyl hydroxamic acid)] It is a compound of. Niacinamide is preferred.

[0094] Examples of vitamin B3 derivatives that can be mentioned include, for example, nicotinic acid esters such as tocopherol nicotinate, amides derived from niacinamide by substitution of the hydrogen group of -CONH2, products from the reaction of carboxylic acids and amino acids, and esters of nicotinyl alcohol with carboxylic acids such as acetic acid, salicylic acid, glycolic acid, or palmitic acid.

[0095] The following derivatives can also be mentioned: 2-chloronicotinamide, 6-methylnicotinamide, 6-aminonicotinamide, N-methylnicotinamide, N,N-dimethylnicotinamide, N-(hydroxymethyl)nicotinamide, quinolinic acid imide, nicotinylanilide, N-benzylnicotinamide, N-ethylnicotinamide, phenazone, nicotinaldehyde, isonicotinic acid, methyl isonicotinic acid, thionicotinamide, nialamide, 2-mercaptonicotinic acid, nicomol and niaprazine, methyl nicotinate and sodium nicotinate.

[0096] Other vitamin B3 derivatives that can also be mentioned include its inorganic salts, such as chloride salts, bromide salts, iodide salts, or carbonate salts, and its organic salts, such as salts obtained by reaction with carboxylic acids, such as acetate salts, salicylate salts, glycolate salts, lactate salts, malate salts, citrate salts, mandelate salts, tartrate salts, etc.

[0097] In a preferred embodiment, at least one compound selected from vitamin B3 and its derivatives in the composition of the present invention is niacinamide.

[0098] The amount of at least one compound selected from (2) vitamin B3 and its derivatives in the composition according to the present invention may be 0.06% by mass or more, preferably 0.3% by mass or more, more preferably 0.6% by mass or more, based on the total mass of the composition.

[0099] On the other hand, the amount of at least one compound selected from (2) vitamin B3 and its derivatives in the composition according to the present invention may be 60% by mass or less, preferably 30% by mass or less, more preferably 18% by mass or less, based on the total mass of the composition.

[0100] The amount of at least one compound selected from (2) vitamin B3 or its derivatives in the composition according to the present invention may be in the range of 0.06% by mass to 60% by mass, preferably 0.3% by mass to 30% by mass, more preferably 0.6% by mass to 18% by mass, based on the total mass of the composition.

[0101] The mass ratio of the amount of at least one compound selected from (2) vitamin B3 and its derivatives to the amount of (1) thiopyridone compound in the composition according to the present invention may be 6 or more, preferably 8 or more, more preferably 10 or more.

[0102] The mass ratio of the amount of at least one compound selected from (2) vitamin B3 and its derivatives to the amount of (1) thiopyridone compound in the composition according to the present invention may be 20 or less, preferably 15 or less, more preferably 12 or less.

[0103] The mass ratio of the amount of at least one compound selected from (2) vitamin B3 and its derivatives to the amount of (1) thiopyridone compound in the composition according to the present invention may be in the range of 6 to 20, preferably 8 to 15, more preferably 10 to 12.

[0104] (pH regulator) The composition according to the present invention may contain (3) at least one pH adjuster. Two or more pH adjusters may be used in combination. Therefore, a single type of pH adjuster or a combination of different types of pH adjusters may be used.

[0105] (3) As the pH adjuster, at least one acidifying agent and / or at least one basifying agent (alkali agent) may be used.

[0106] The acidifying agent may be a monovalent or polyvalent acid, for example, a divalent acid.

[0107] The acidifying agent can be, for example, a mineral acid (inorganic acid) such as hydrochloric acid, sulfuric acid, phosphoric acid, or an organic acid such as a carboxylic acid, examples of which include tartaric acid, citric acid, and lactic acid, and sulfonic acid.

[0108] The basifying agent may be a monovalent or polyvalent base, for example, a divalent base.

[0109] The basifying agent can be mineral (inorganic), organic, or a mixture.

[0110] The inorganic basifying agent can be selected from aqueous ammonia, alkali metal carbonates or bicarbonates such as sodium carbonate or potassium carbonate and sodium bicarbonate or potassium bicarbonate, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and mixtures thereof.

[0111] The organic basifying agent can be selected from organic amines having a pKb of less than 12, preferably less than 10, and more preferably less than 6 at 25°C. It should be noted that this is the pKb corresponding to the function of the highest basicity. In addition, the organic amine does not contain any alkyl or alkenyl fatty chain containing more than 10 carbon atoms.

[0112] The organic basifying agent is, for example, alkanolamine, oxyethylenated and / or oxypropylenated ethylenediamine, amino acid, and the following formula (III):

[0113]

Chem.

[0114] (wherein, W represents a divalent C1-C6 alkylene group optionally substituted with one or more hydroxyl groups or C1-C6 alkyl groups and optionally interrupted by one or more heteroatoms such as O and N, R x , R y , R z , and R t may be the same or different and each represents a hydrogen atom or a C1-C6 alkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl group) can be selected from amine compounds of

[0115] Examples of the amine compounds of formula (III) that can be enumerated include 1,3-diaminopropane, 1,3-diamino-2-propanol, spermine, and spermidine.

[0116] The term "alkanolamine" means an organic amine containing a primary, secondary, or tertiary amine functional group and one or more linear or branched C1-C8 alkyl groups having one or more hydroxyl groups.

[0117] Alkanolamines such as monoalkanolamine, dialkanolamine or trialkanolamine containing one to three identical or different C1-C4 hydroxyalkyl groups may be suitable for the present invention. Among this type of compounds, mention may be made of monoethanolamine (MEA), diethanolamine, triethanolamine, monoisopropanolamine, 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.

[0118] The amino acids that can be used are those of natural or synthetic origin in their L-form, D-form, or racemic form, and more specifically, contain at least one acid functional group selected from each functional group of carboxylic acid, sulfonic acid, phosphonic acid or phosphoric acid. The amino acid may be in a neutral form or an ionic form.

[0119] Particularly mentionable as the amino acids that can be used in the present invention are aspartic acid, glutamic acid, alanine, arginine, ornithine, citrulline, asparagine, carnitine, cysteine, glutamine, glycine, histidine, lysine, isoleucine, leucine, methionine, N-phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine.

[0120] The amino acid may preferably be a basic amino acid containing an additional amine functional group optionally contained in a ring or ureido functional group.

[0121] Such basic amino acids preferably have the following formula (IV):

[0122]

Chemical formula

[0123] (wherein R is as follows:

[0124] [Chemical formula]

[0125] -(CH2)3-NH2, -(CH2)2-NH2, -(CH2)2-NH-CO-NH2, and

[0126] [Chemical formula]

[0127] represents a group selected from) can be selected from those corresponding to.

[0128] Examples of the compound corresponding to formula (IV) include histidine, lysine, arginine, ornithine, and citrulline.

[0129] The organic basic agent can be selected from heterocyclic organic amines. In addition to histidine already mentioned in the amino acid, in particular, pyridine, piperidine, imidazole, triazole, tetrazole, and benzimidazole can be mentioned.

[0130] The organic basic agent can also be selected from amino acid dipeptides. Examples of the amino acid dipeptides that can be used in the present invention include carnosine, anserine, and balenine.

[0131] The organic basic agent can also be selected from compounds containing a guanidine functional group. As this type of amine that can be used in the present invention, in addition to arginine already mentioned as an amino acid, in particular, creatine, creatinine, 1,1-dimethylguanidine, 1,1-diethylguanidine, glycocyamine, metformin, agmatine, N-amidinolalanine, 3-guanidinopropionic acid, 4-guanidinobutyric acid, and 2-([amino(imino)methyl]amino)ethane-1-sulfonic acid can be mentioned.

[0132] In a preferred embodiment of the present invention, the organic basic agent can be selected from amino acids, preferably basic amino acids, more preferably arginine, lysine, histidine, or a mixture thereof. Even more preferentially, the organic basic agent may be arginine.

[0133] The hybrid compounds that can be mentioned include salts of acids such as carbonic acid or hydrochloric acid and the aforementioned amines. In particular, guanidine carbonate or monoethanolamine hydrochloride can be used.

[0134] (3) The pH adjuster may be present in an amount of 0.01% by mass or more, preferably 0.05% by mass or more, more preferably 0.1% by mass or more, based on the total mass of the composition.

[0135] (3) The pH adjuster may be present in an amount of 15% by mass or less, preferably 10% by mass or less, more preferably 5% by mass or less, based on the total mass of the composition.

[0136] (3) The pH adjuster may be present in an amount in the range of 0.01% by mass to 15% by mass, preferably 0.05% by mass to 10% by mass, more preferably 0.1% by mass to 5% by mass or less, based on the total mass of the composition.

[0137] The composition according to the present invention preferably has a pH of 4.5 or more, more preferably 5 or more.

[0138] The composition according to the present invention preferably has a pH of 6.5 or less, more preferably 6 or less.

[0139] The composition according to the present invention preferably has a pH of 4.5 to 6.5, more preferably 5 to 6.

[0140] The pH of the composition means the pH of the aqueous phase of the composition according to the present invention.

[0141] In addition, in order to stabilize the pH of the composition according to the present invention, it may be preferable to use at least one buffer or buffering agent in combination with an acidifying agent and / or a basifying agent as (3) a pH regulator.

[0142] As the buffer, any generally known buffer may be used. For example, salts of acids or bases, preferably salts of weak acids or weak bases, may be used. For example, when citric acid or lactic acid is used as the acidifying agent, sodium citrate or sodium lactate may be used as the buffer.

[0143] (Water) The composition according to the present invention may contain (4) water.

[0144] The amount of (4) water in the composition according to the present invention may be 50% by mass or more, preferably 55% by mass or more, more preferably 60% by mass or more, based on the total mass of the composition.

[0145] On the other hand, the amount of (4) water in the composition according to the present invention may be 99% by mass or less, preferably 95% by mass or less, more preferably 90% by mass or less, based on the total mass of the composition.

[0146] The amount of (4) water in the composition according to the present invention may be 50% to 99% by mass, preferably 55% to 95% by mass, more preferably 60% to 90% by mass, based on the total mass of the composition.

[0147] (Caffeine) In certain embodiments of the present invention, the composition according to the present invention may further contain (5) caffeine.

[0148] (5) Caffeine may be present in an amount of 0.01% by mass or more, preferably 0.5% by mass or more, more preferably 1% by mass or more, based on the total mass of the composition.

[0149] (5) Caffeine may be present in an amount of 15% by mass or less, preferably 10% by mass or less, more preferably 5% by mass or less, based on the total mass of the composition.

[0150] (5) Caffeine may be present in an amount in the range of 0.01% by mass to 15% by mass, preferably 0.5% by mass to 10% by mass, more preferably 1% by mass to 5% by mass or less, based on the total mass of the composition.

[0151] In certain embodiments of the present invention, the composition of the present invention contains (1) the thiopyridinone compound disclosed above, (2) at least one compound selected from vitamin B3 and its derivatives, and (3) caffeine.

[0152] (Other optional additives) The composition according to the present invention may also contain any other optional additives commonly used in the cosmetic field, selected from, for example, solvents, chelating agents, cosmetic active agents other than component (1), such as oils, preservatives, and mixtures thereof.

[0153] It is a common practice for those skilled in the art to adjust the nature and amount of the above-mentioned optional additives that may be present in the composition according to the present invention so that the desired cosmetic properties are not affected by the additives.

[0154] Examples of the solvent include one or several kinds of organic solvents acceptable as cosmetics, such as alcohols, especially monohydric alcohols like ethyl alcohol, isopropyl alcohol, benzyl alcohol and phenylethyl alcohol; diols such as ethylene glycol, propylene glycol and butylene glycol; other polyols such as glycerol, sugars and sugar alcohols; and ethers such as ethylene glycol monomethyl, monoethyl and monobutyl ethers, propylene glycol monomethyl, monoethyl and monobutyl ethers, and butylene glycol monomethyl, monoethyl and monobutyl ethers.

[0155] The organic solvent may be present at a concentration of 0.01% to 30% by mass, preferably 0.1% to 20% by mass, more preferably 1% to 10% by mass, based on the total mass of the composition.

[0156] [Preparation] The composition according to the present invention can be prepared by mixing the above essential components and optional components by a conventional method.

[0157] For example, the composition according to the present invention (1) at least one thiopyridone compound and (2) at least one compound selected from vitamin B3 and its derivatives can be prepared by a method including the step of mixing them.

[0158] It is also possible to further mix any of the optional components.

[0159] The mixing can be carried out at any temperature such as room temperature (e.g., 20 to 25°C, preferably 25°C), preferably at a temperature of 30°C or higher, preferably 40°C or higher, more preferably 50°C or higher.

[0160] The form of the composition according to the present invention is not particularly limited and may take various forms such as W / O emulsion, O / W emulsion, gel, solution, etc. It is preferred that the composition according to the present invention is in the form of an emulsion, preferably an O / W emulsion, more preferably an O / W gel emulsion or a gel.

[0161] [Beauty method] The composition according to the present invention can be used as a cosmetic or dermatological composition, preferably a cosmetic composition, more preferably a cosmetic composition for keratinous substances. Examples of keratinous substances include the skin, scalp, hair, mucous membranes such as the lips, and nails.

[0162] The composition according to the present invention can be used as a depigmentation, bleaching or whitening product for keratinous substances such as the skin. In particular, the composition according to the present invention can be used as a whitening product.

[0163] The composition according to the present invention is preferably intended for application to keratinous substances such as the skin, scalp, and / or lips, preferably the skin.

[0164] Therefore, the composition according to the present invention can be used in a beauty method for keratinous substances, preferably the skin. In one embodiment, the present invention relates to a beauty method, preferably a whitening method, for keratinous substances, preferably the skin, comprising the step of applying the composition according to the present invention to the keratinous substance.

[0165] The composition according to the present invention can be used as a topical cosmetic composition in the form of a lotion, milk, cream, gel, paste, serum, foam substance or spray.

[0166] [Use] The present invention relates to (1) a compound of the following formula (I), a tautomer of the following formula (I')

[0167] [Chemical formula]

[0168] (wherein, R1 is a) a hydrogen atom, and b) one or more groups selected from i) -O-R3 and ii) -S-R3 optionally substituted with one or more groups selected from saturated linear C1-C 10 or branched C3-C 10 alkyl group selected from, R2 is a) a hydrogen atom, b) one or more groups selected from i) -O-R3, ii) -S-R3, iii) -C(O)-O-R3, and iv) C5-C 12 aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups selected from saturated linear C1-C 12 or branched C3-C 12 or cyclic C3-C8 hydrocarbon group, and c) a group selected from C5-C 12 aryl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups selected from, R3 is a) a hydrogen atom, and b) a group selected from saturated linear C1-C 10 or branched C3-C 10 alkyl group selected from), in a composition comprising at least one compound selected from these salts, solvates such as hydrates thereof, these optical isomers, these racemates, and mixtures thereof, the use of at least one compound selected from (2) vitamin B3 and derivatives thereof, (1) Regarding the use for solubilizing a compound.

[0169] The term "solubilize" has the same meaning as enhancing solubility.

[0170] The use according to the present invention can enhance the solubility of (1) a thiopyridone compound in a composition containing the thiopyridone compound. Therefore, the resulting composition is not turbid. Thus, the enhanced solubility of the (1) thiopyridone compound in the composition of the present invention makes this composition stable and transparent.

[0171] The above description regarding the (1) thiopyridone compound and at least one compound selected from (2) vitamin B3 and its derivatives for the composition according to the present invention may also be applicable to those used in the use according to the present invention.

[0172] The composition in the use according to the present invention can contain any of the optional components described above regarding the composition according to the present invention.

Examples

[0173] The present invention will be described in more detail by way of examples. However, these examples should not be construed as limiting the scope of the present invention.

[0174] (Examples 1 - 3 and Comparative Examples 1 - 2) [Preparation] Each of the compositions according to Examples 1 - 3 and Comparative Examples 1 - 2 was prepared by mixing the components shown in Table 1 (Table 8). All numerical values regarding the amounts of the components are based on "mass%" as the active material.

[0175] To evaluate the solubilization of the thiopyridinone compound 20 according to the present invention, screening tests were carried out using niacinamide or using niacinamide and caffeine. In the test, the thiopyridinone compound 20 was mixed with niacinamide at room temperature using a magnetic stirrer in combination with the raw materials disclosed in Examples 1 to 3 or Comparative Examples 1 to 2 and observed for the next 90 minutes.

[0176] The appearance of the mixture was analyzed to look for floating or decanted particles and compared with pure thiopyridinone compound 20.

[0177]

Table 8

[0178] Comparative Examples 1 and 2 did not exist in a uniform appearance (turbid) after the solubilization protocol.

[0179] Regarding Examples 1 to 3, the composition showed a uniform and transparent appearance.

Claims

1. (1) A compound of the following formula (I), a tautomer of the following formula (I') 【Chemical 1】 (wherein R 1 is a) a hydrogen atom, and b) groups selected from those which may be the same or different i)-O-R 3 and ii)-S-R 3 optionally substituted by one or more groups selected from saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group are shown, R 2 is a) a hydrogen atom, b) groups selected from those which may be the same or different i)-O-R 3 、 ii)-S-R 3 、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with an alkoxy group having C 5 -C 12 aryl group optionally substituted with one or more groups selected from saturated linear C 1 ~C 12 or branched C 3 ~C 12 or cyclic C 3 ~C 8 hydrocarbon groups, and c) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with an alkoxy group of C 5 -C 12 aryl group are shown, R 3 is a) a hydrogen atom, and b) Saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group groups selected from) at least one compound selected from these salts, solvates such as their hydrates, these optical isomers, these racemates, and mixtures thereof, and (2) at least one compound selected from vitamin B3 and its derivatives comprising a composition, preferably a cosmetic composition.

2. R of formula (I) and (I') 1 represents a hydrogen atom, or or R of formula (I) and (I') 1 is a linear (C 1 ~C 10 ) alkyl group or a branched (C 3 ~C 10 ) alkyl group, particularly a linear (C 1 ~C 6 ) alkyl group or a branched (C 3 ~C 6 ) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, and particularly the alkyl group of R 1 is unsubstituted, the composition according to claim 1.

3. R of formula (I) and (I') 2 represents a hydrogen atom, or or R of formula (I) and (I') 2 is a linear (C 1 -C 10 ) alkyl group or a branched (C 3 -C 10 ) alkyl group, particularly a linear (C 1 -C 6 ) alkyl group or a branched (C 3 -C 6 ) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably a methyl or ethyl group, and the alkyl group of R 2 is unsubstituted the composition according to claim 1 or 2.

4. R in formula (I) and (I') 2 is a linear (C 1 -C 10 ) alkyl group or a branched (C 3 -C 10 ) alkyl group, particularly a linear (C 1 -C 6 ) alkyl group or a branched (C 3 -C 6 ) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, and the alkyl group is substituted with one or more groups selected from i), ii), iii) and iv) as defined above, preferably, the alkyl group is substituted with one or two groups selected from i), ii) and iii), more preferably, one or two groups selected from i) and iii), and even more preferably, substituted with one group iii) as carboxy. The composition according to claim 1 or 2.

5. R of formula (I) and (I') 2 is a (C 3 to C 8 ) cycloalkyl group, preferably a (C 5 to C 7 ) cycloalkyl group, for example, represents cyclohexyl, or or R of formula (I) and (I') 2 is a C 1 to C 8 aryl group optionally substituted with one or more hydroxyls and / or one or more C 5 to C 12 alkoxy groups, preferably an unsubstituted phenyl group, the composition according to claim 1 or 2.

6. R of formula (I) and (I') 3 represents a hydrogen atom, or or R of formula (I) and (I') 3 is a saturated straight-chain C 1 -C 10 or branched C 3 -C 10 alkyl group, especially a straight-chain (C 1 -C 6 ) alkyl group or a branched (C 3 -C 6 ) alkyl group, preferably a (C 1 -C 4 ) alkyl group, such as a methyl group the composition according to any one of claims 1 to 5.

7. R of formula (I) and (I') 1 is a) a hydrogen atom, and b) groups which may be the same or different i)-O-R 3 and ii)-S-R 3 (preferably substituted optionally by one or more groups i)) optionally substituted by one or more groups selected from saturated straight-chain C 1 ~C 6 or branched C 3 ~C 6 alkyl group represent groups selected from, R of formulas (I) and (I') 2 is a) a hydrogen atom, and b) groups which may be the same or different i)-O-R 3 、 ii)-S-R 3 、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 ~C 4 alkoxy group, for example a phenyl group optionally substituted with methoxy by one or more groups selected from, preferably one or more groups selected from i) and iii), preferably one or more groups substituted by iii) such as carboxy Optionally substituted saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 or cyclic C 3 ~C 8 such as C 5 ~C 6 hydrocarbon group represent groups selected from, R of formula (I) and (I') 3 is a) a hydrogen atom, and b) Saturated straight-chain C 1 ~C 6 or branched C 3 ~C 6 alkyl group groups selected from represent, Preferably, the compound of formula (I) and the tautomer (I'), these salts, these solvates such as their hydrates, these optical isomers, these racemates, and mixtures thereof have the following meanings: R of formula (I) and (I') 1 is a) a hydrogen atom, and b) which may be the same or different, i)-OR 3 optionally substituted with one or more groups selected from, more preferably unsubstituted, saturated straight-chain C 1 ~C 4 or branched C 3 ~C 4 alkyl group groups selected from represent, R of formula (I) and (I') 2 is a) a hydrogen atom, and b) groups which may be the same or different i)-O-R 3 、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 -C 4 aryl group optionally substituted with an alkoxy group having C 5 -C 12 aryl group optionally substituted by one or more groups selected from, saturated linear C 1 -C 10 or branched C 3 -C 10 or cyclic C 3 -C 8 , for example C 5 -C 6 hydrocarbon group represent groups selected from, R of formula (I) and (I') 3 is a) a hydrogen atom, and b) Saturated straight-chain C 1 ~C 4 or branched C 3 ~C 4 alkyl group, such as methyl or ethyl groups selected from represent, the composition according to any one of claims 1 to 6.

8. (1) The composition according to any one of claims 1 to 7, wherein the compound is selected from the following compounds 1 to 24, their tautomers, their salts, their solvates such as hydrates, their optical isomers, their racemates, and mixtures thereof, particularly compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20 or 21, more specifically 1, 9, 16, 18, 19, 20 or 21, preferably 18, 19, 20 or 21, and more preferably 20. 【Table 1A】 【Table 1B】 【Table 1C】 【Table 1D】

9. The composition according to any one of claims 1 to 8, wherein the amount of the compound (1) in the composition is 0.01% by mass to 10% by mass, preferably 0.05% by mass to 5% by mass, more preferably 0.1% by mass to 3% by mass based on the total mass of the composition.

10. The composition according to any one of claims 1 to 9, wherein the amount of at least one compound selected from vitamin B3 and its derivatives (2) in the composition is 0.06% by mass to 60% by mass, preferably 0.3% by mass to 30% by mass, more preferably 0.6% by mass to 18% by mass based on the total mass of the composition.

11. The composition according to any one of claims 1 to 10, wherein at least one compound selected from vitamin B3 and its derivatives (2) is selected from nicotinamide, niacin, nicotinyl alcohol, nicotinicuric acid, nicotinyl hydroxamic acid, 2-chloronicotinamide, 6-methylnicotinamide, 6-aminonicotinamide, N-methylnicotinamide, N,N-dimethylnicotinamide, N-(hydroxymethyl)nicotinamide, quinolinic imide, nicotinanilide, N-benzylnicotinamide, N-ethylnicotinamide, phenazone, nicotinaldehyde, isonicotinic acid, methyl isonicotinic acid, thionicotinamide, nialamide, 2-mercaptonicotinic acid, nicomol and niaprazine, methyl nicotinate and sodium nicotinate, and mixtures thereof, preferably nicotinamide.

12. The composition according to any one of claims 1 to 11, further comprising caffeine in an amount in the range of 0.01% by mass to 15% by mass, preferably 0.5% by mass to 10% by mass, more preferably 1% by mass to 5% by mass based on the total mass of the composition.

13. The composition according to any one of claims 1 to 12, which is a keratin substance, preferably for whitening the skin.

14. A keratin substance, preferably a cosmetic method for the skin, preferably a whitening method, comprising: the step of applying the composition according to any one of claims 1 to 13 to the keratin substance A method comprising.

15. (1) A compound of the following formula (I), a tautomer of the following formula (I') 【Chemical 2】 (wherein R 1 is a) a hydrogen atom, and b) groups selected from the same or different i)-O-R 3 and ii)-S-R 3 optionally substituted by one or more groups selected from saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl groups is shown, R 2 is a) a hydrogen atom, b) the same or different i)-O-R 3 、 ii)-S-R 3 、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with an alkoxy group having C 5 -C 12 aryl group optionally substituted by one or more groups selected from a saturated linear C 1 ~C 12 or branched C 3 ~C 12 or cyclic C 3 ~C 8 hydrocarbon group, and c) one or more hydroxyl and / or one or more C 1 to C 8 aryl group optionally substituted with an alkoxy group of C 5 to C 12 aryl group represents a group selected from, R 3 is a) a hydrogen atom, and b) Saturated linear C 1 ~C 10 or branched C 3 ~C 10 alkyl group represents a group selected from), in a composition comprising at least one compound selected from these salts, solvates such as hydrates thereof, these optical isomers, these racemates, and mixtures thereof, the use of at least one compound selected from (2) vitamin B3 and derivatives thereof, (1) for solubilizing the compound.

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