FR3136667A1 - STABILIZATION OF THIOPYRIDINONE COMPOUND AND COMPOSITION COMPRISING IT - Google Patents

Abstract

STABILIZATION OF THIOPYRIDINONE COMPOUND AND COMPOSITION COMPRISING SAME The present invention relates to a composition comprising: (1) at least one thiopyridinone compound; and (2) at least one chelating agent. The present invention can provide a composition including (1) thiopyridinone compound(s) exhibiting increased stability of the (1) thiopyridinone compound(s) over time, particularly even when the composition is maintained for a period of time. relatively long period at high temperature. Figure for the abstract: None

Description

STABILIZATION OF THIOPYRIDINONE COMPOUND AND COMPOSITION COMPRISING IT

The present invention relates to the stabilization of a thiopyridinone compound in a composition including the thiopyridinone compound.

CONTEXT OF ART

At various times in their lives, some people notice the appearance on their skin, and more particularly on their face and hands, of darker and/or more colored spots, which give a heterogeneous appearance to their skin. These spots are particularly due to a high concentration of melanin in the keratinocytes located on the surface of the skin.

The use of harmless topical depigmentation substances with good effectiveness is particularly desired for the purpose of treating pigmentation spots.

For example, arbutin, niacinamide and kojic acid are known as skin depigmentation agents.

Furthermore, document WO2017/102349 discloses a new depigmentation or whitening agent, namely, a thiopyridinone compound. The compound thiopyridinone may exhibit strong depigmentation or whitening effects by reducing melanin production.

DISCLOSURE OF THE INVENTION

However, it has been found that a thiopyridinone compound tends to destabilize in a composition over time, particularly when the composition including the thiopyridinone compound is held for a relatively long period of time at an elevated temperature.

Thus, an objective of the present invention is to provide a composition including thiopyridinone compound(s) exhibiting increased stability of the thiopyridinone compound(s) over time, particularly when the composition is maintained for a period of relatively long time at high temperature.

The above objective can be achieved by a composition comprising:

(1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I') below, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures:

(I)

(I’)

in which

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

And

R ₂ designates a radical chosen from

a) a hydrogen atom,

b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and

c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals

in which

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group;

And

(2) at least one chelating agent.

It may be preferable that:

R ₁ of formula (I) and (I') represents a hydrogen atom;

Or

R ₁ of formula (I) and (I') represents a linear (C ₁ -C ₁₀ ) or branched (C ₃ -C ₁₀ ) alkyl group, in particular a linear alkyl group (C ₁ -C ₆ ) or branched (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, in particular said alkyl group of R ₁ is not substituted.

It may be preferable that:

R ₂ of formula (I) and (I') represents a hydrogen atom;

Or

R ₂ of formula (I) and (I') represents a linear (C ₁ -C ₁₀ ) or branched (C ₃ -C ₁₀ ) alkyl group, in particular a linear alkyl group (C ₁ -C ₆ ) or branched (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R ₂ not being substituted.

It may be preferable that:

R ₂ of formula (I) and (I') represents a linear alkyl group (in C ₁ -C ₁₀ ) or a branched alkyl group (in C ₃ -C ₁₀ ), in particular a linear alkyl group (in C ₁ -C ₆ ) or a branched alkyl group (C ₃ -C ₆ ), 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 above, preferably said alkyl group being substituted by one or two groups chosen from i), ii) and iii), more preferably by one or two groups chosen from i) and iii), better substituted by a group iii) such as carboxy.

It may be preferable that:

R ₂ of formula (I) and (I') represents a cycloalkyl group (C ₃ -C ₈ ), preferably a cycloalkyl group (C ₅ -C ₇ ) such as cyclohexyl;

Or

R ₂ of formula (I) and (I') represents a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, preferably a phenyl group in particular unsubstituted.

It may be preferable that:

R ₃ of formula (I) and (I') represents a hydrogen atom;

Or

R ₃ of formula (I) and (I') represents a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group; in particular a linear alkyl group (in C ₁ -C ₆ ) or a branched alkyl group (in C ₃ -C ₆ ), preferably an alkyl group (in C ₁ -C ₄ ) such as a methyl group.

It may be more preferable that:

R ₁ of formula (I) and (I') represents a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₆ or branched C ₃ -C ₆ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

preferably optionally substituted with one or more groups i);

R ₂ of formula (I) and (I') represents a radical chosen from

a) a hydrogen atom, and

b) a linear saturated hydrocarbon group in C₁-VS₁₀or branched in C₃-VS₁₀or cyclic in C₃-VS₈such than in C₅-VS₆, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a phenyl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₄ alkoxy radicals such as methoxy,

preferably substituted by one or more groups chosen from i) and iii), preferably iii) such as carboxy; And

R ₃ of formula (I) and (I') represents a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₆ or branched C ₃ -C ₆ alkyl group,

preferentially, the compounds of formula (I) and the tautomer (I’), their salts, solvates, such as hydrates, their optical isomers, their racemates, and their mixtures, have the following meanings:

R ₁ of formula (I) and (I') represents a radical chosen from:

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from i) -OR _3, more preferably unsubstituted;

R ₂ of formula (I) and (I') represents a radical chosen from

a) a hydrogen atom, and

b) a linear saturated hydrocarbon group in C ₁ -C ₁₀ or branched in C ₃ -C ₁₀ or cyclic in C ₃ -C ₈ such as in C ₅ -C ₆ , optionally substituted by one or more groups, which can be identical or different, chosen from

i) -OR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₄ alkoxy radicals; And

R ₃ of formula (I) and (I') represents a radical chosen from:

a) a hydrogen atom;

b) a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ alkyl group such as methyl or ethyl.

Compound (1) can be chosen from compounds 1 to 24 below, their tautomers, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures, 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, and more preferably 20:

The quantity of compound(s) (1) in the composition according to the present invention may be from 0.01% to 10% by weight, preferably from 0.05% to 5% by weight, and more preferably from 0 .1% to 3% by weight, relative to the total weight of the composition.

The chelating agent (2) can be chosen from organic chelating agents, preferably aminocarboxylic acids and their salts, hydroxycarboxylic acids and their salts, and mixtures thereof, and more preferably aminocarboxylic acids and their salts.

The chelating agent (2) can be chosen from the group consisting of EDTA and its salts, citric acid and its salts, N,N-bis(carboxymethyl)-L-glutamic acid and its salts, metaphosphates, and their mixtures.

The quantity of the chelating agent(s) (2) in the composition according to the present invention may be from 0.01% to 3% by weight, preferably from 0.05% to 2% by weight, plus preferably from 0.1% to 1% by weight, relative to the total weight of the composition.

The composition according to the present invention may be intended for whitening a keratinous material, preferably the skin.

The present invention also relates to a cosmetic process, preferably a whitening process, for a keratinous material, preferably skin, comprising the following step:

the application to the keratinous material of the composition according to the present invention.

Another aspect of the present invention is a use of (2) at least one chelating agent in a composition comprising (1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I' ) below, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures:

(I)

(I’)

in which

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

And

R ₂ designates a radical chosen from

a) a hydrogen atom,

b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and

c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals

in which

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group

in order to stabilize the compound(s) (1).

After extensive research, the inventors have discovered that it is possible to provide a composition including a thiopyridinone compound or thiopyridinone compounds exhibiting increased stability of the thiopyridinone compound(s) over time, particularly even when the composition is maintained for a relatively long period of time at elevated temperature.

Thus, the composition according to the present invention comprises:

(1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I') below, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures (hereinafter, the compound is called “thiopyridinone compound”):

(I)

(I’)

in which

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

And

R ₂ designates a radical chosen from

a) a hydrogen atom,

b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and

c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals

in which

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group;

And

(2) at least one chelating agent.

The composition according to the present invention may exhibit increased stability of the thiopyridinone compound (1) therein.

That is, the composition according to the present invention can increase the stability of the thiopyridinone compound (1) therein. The term "stability" of the thiopyridinone compound (1) can be determined by the change in the amount of the thiopyridinone compound (1) in the composition according to the present invention during a certain period of time. Increased “stability ” means that the change in the amount of the thiopyridinone compound (1) over time is more limited.

The composition according to the present invention can exhibit increased stability of the thiopyridinone compound (1) therein, even when the composition is maintained for a relatively long period of time such as two weeks at an elevated temperature such as 55 ºC.

Therefore, the composition according to the present invention can be stored for a long period of time even under hot conditions.

Additionally, the increased stability of the thiopyridinone compound (1) may provide improved or increased bioavailability of the thiopyridinone compound (1) which may function as a depigmentation or bleaching agent. Therefore, the composition according to the present invention can provide increased or improved depigmentation or whitening effects.

Hereinafter, the composition, use and the like according to the present invention will be described in detail.

[Composition]

The composition according to the present invention comprises:

(1) at least one thiopyridinone compound; And

(2) at least one chelating agent.

The thiopyridinone compound (1) and the chelating agent (2), as well as the other particularities of the composition according to the present invention will be explained below.

(Thiopyridinone compound)

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

The thiopyridinone compound (1) is chosen from the compounds of formula (I) below, the tautomers of formula (I') below, their salts, their solvates, such as their hydrates, their optical isomers, their racemates and their mixtures:

(I)

(I’)

in which

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

And

R ₂ designates a radical chosen from

a) a hydrogen atom,

b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and

c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals

in which

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group.

Hereinafter, within the meaning of the present invention and unless otherwise indicated:

a "saturated, linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ " hydrocarbon group is equivalent to a "linear (C ₁ -C ₁₂ ) or branched (C ₃ -C ₁₂ ) alkyl group" which corresponds to a saturated hydrocarbon group, linear in C ₁ -C ₁₂ or branched in C ₃ -C ₁₂ , preferably a linear hydrocarbon group in C ₁ -C ₁₀ or branched in C ₃ -C ₁₀ , and more preferably a hydrocarbon group linear in C ₁ -C ₆ or branched in C ₃ -C ₆ ; Preferably, the linear or branched groups can be chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl groups; More preferably, the saturated alkyl groups, linear or branched, can 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;

- a saturated hydrocarbon group “cyclic in C₃-VS₈» is a group mono or bicyclic cycloalkyl containing from 3 to 8 carbon atoms, and in particular is a C monocyclic cycloalkyl group₅to C₇such as a cyclohexyl group,

- an “alkoxy radical” is an alkyl-oxy radical for which the alkyl radical is a linear or branched C ₁ -C ₁₆ hydrocarbon radical, and preferably a C ₁ -C ₈ hydrocarbon radical;

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

- an “aryl” group represents a carbon-based group, monocyclic or bicyclic, 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;

- the term “at least one” is equivalent to the term “one or more”; And

- the term “inclusive” for a concentration range means that the limits of this range are included in the defined range.

The salts of the compounds of formula (I), (I'), (II), or (II') as defined below include conventional non-toxic salts of said compounds, such as those formed from an organic acid or inorganic or of an organic or inorganic base.

As salts of compounds of formula (I), (I’), (II) or (II’), we can cite:

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

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

Or

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 thus comprise, for example, one or more alcohol functions. Mention may be made in particular of 2-amino-2-methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol and 3-(dimethylamino)propylamine. .

We can also cite salts of amino acids, 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) can be chosen from alkali or alkaline earth metal salts such as sodium, potassium, calcium or magnesium salts and ammonium salts.

An “organic or inorganic acid salt” is more particularly chosen from salts chosen from a salt derived from i) hydrochloric acid HCl, ii) hydrobromic acid HBr, iii) sulfuric acid H ₂ SO ₄ , iv) alkylsulfonic acids: Alk -S(O) ₂ OH such as methanesulfonic acid and ethanesulfonic acid; v) arylsulfonic acids: Ar-S(O) ₂ OH 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 H ₃ PO ₄ ; xiii) acetic acid CH ₃ C(O)OH; xiv) triflic acid CF ₃ SO ₃ H; and xv) tetrafluoroboric acid HBF ₄ .

Acceptable solvates of the compounds described in the specification include conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents. We can cite, by way of example, solvates due to the presence of water or linear or branched alcohols, such as ethanol or isopropanol.

Optical isomers are in particular enantiomers and diastereoisomers.

Compound (I’) is the tautomeric form of compound (I) when a tautomeric equilibrium exists according to the following diagram:

According to one embodiment of the present invention, R ₁ represents a hydrogen atom.

According to another embodiment of the present invention, R ₁ represents a linear alkyl group (in C ₁ -C ₁₀ ) or a branched alkyl group (in C ₃ -C ₁₀ ), in particular a linear alkyl group (in C ₁ - C ₆ ) or a branched alkyl group (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl. In particular, said alkyl group of R ₁ is not substituted.

According to one embodiment of the present invention, R ₂ represents a hydrogen atom.

According to one embodiment of the present invention, _R 2 represents a linear (C ₁ -C ₁₀ ) or branched (C ₃ -C ₁₀₎ alkyl group, in particular a linear (C ₁ -C ₆ ) or branched alkyl group (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R ₂ not being substituted.

According to another embodiment of the present invention, R ₂ represents a linear alkyl group (in C ₁ -C ₁₀ ) or a branched alkyl group (in C ₃ -C ₁₀ ), in particular a linear alkyl group (in C ₁ - C ₆ ) or a branched alkyl group (C ₃ -C ₆ ), 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 above. Preferably, said alkyl group being substituted by one or two groups chosen from i), ii) and iii), more preferably by one or two groups chosen from i) and iii), better substituted by a group iii) such as carboxy.

Another variant for the radical R ₂ is that said alkyl group is substituted by a group iv) in particular substituted by a phenyl group.

According to another embodiment of the present invention, R ₂ represents a cycloalkyl group (C ₃ -C ₈ ), preferably a cycloalkyl group (C ₅ -C ₇ ) such as cyclohexyl.

According to another embodiment of the present invention, R ₂ represents a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, preferably a group phenyl in particular unsubstituted.

According to one embodiment, R ₃ represents a hydrogen atom.

According to another embodiment, R ₃ represents a saturated alkyl group, linear at C ₁ -C ₁₀ or branched at C ₃ -C ₁₀ ; in particular a linear (C ₁ -C ₆ ) or branched (C ₃ -C ₆ ) alkyl group, preferably an alkyl group (C ₁ -C ₄ ) such as the methyl group.

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

have the following meanings:

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₆ or branched C ₃ -C ₆ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

preferably optionally substituted with one or more groups i);

R ₂ designates a radical chosen from

a) a hydrogen atom;

b) a linear saturated hydrocarbon group in C₁-VS₁₀or branched in C₃-VS₁₀or cyclic in C₃-VS₈such than in C₅-VS₆optionally substituted by one or more groups, which may be identical or different, chosen from:

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a phenyl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₄ alkoxy radicals such as methoxy,

preferably substituted by one or more groups chosen from i) and iii), preferably iii) such as carboxy; And

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₆ or branched C ₃ -C ₆ alkyl group

Preferably, the compounds of formula (I) and the tautomer (I’) or their salts, their optical isomers, racemates, and/or their solvates such as their hydrates, alone or in mixture

have the following meanings:

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ alkyl group optionally substituted by one or more groups, which may be the same or different, chosen from i) -OR _3, more preferably unsubstituted;

R ₂ designates a radical chosen from

a) a hydrogen atom; And

b) a linear saturated hydrocarbon group in C₁-VS₁₀or branched in C₃-VS₁₀or cyclic in C₃-VS₈such than in C₅-VS₆, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

iii) -C(O)-OR ₃ ,

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₄ alkoxy radicals; And

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ alkyl group such as methyl or ethyl.

Preferably, the compounds of formula (I) and the tautomer (I’) or their salts, their optical isomers, racemates, and/or their solvates such as their hydrates, alone or in mixture

have the following meanings:

R ₁ is a hydrogen atom; And

R ₂ designates a radical chosen from

a) a hydrogen atom, and

b) a linear saturated hydrocarbon group in C ₁ -C ₅ or branched in C ₃ -C ₅ or cyclic in C ₃ -C ₈ such as in C ₅ -C ₆ , substituted by one or more groups, which may be identical or different, chosen from v) -C(O)-OR ₃ , preferably substituted by a group iii) -C(O)-OR ₃ ; R ₂ is even more preferably a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ hydrocarbon group substituted by a group iii) -C(O)-OR ₃ ; And

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₄ or branched C ₃ -C ₄ alkyl group such as methyl or ethyl.

According to another preferred embodiment, the compounds of formula (I) and the tautomer (I') are chosen from the compounds of formula (II) below and also their tautomers of formula (II') below, their salts, their solvates and their optical isomers, and their racemates, alone or in mixture:

In formulas (II) and (II') R ₁ and R ₃ have the same meaning as R ₁ and R ₃ in the compounds of formula (I) and (I') and X designates an alkylene radical -(CH ₂ ) _n - with n being an integer ranging from 1 to 10 inclusive, preferably ranging from 1 to 6, more preferably ranging from 1 to 4, such that 1, preferably R ₃ represents a hydrogen atom.

Among the compounds of formula (I), the following compounds are preferably used, and their tautomer (I') or their salts, their optical isomers, racemates and/or their solvates such as their hydrates, alone or in mixture;

Among these compounds, the following compounds are more particularly preferred:

More preferably, among these compounds, the following compounds are more particularly preferred:

Even more preferably, among these compounds, the following compounds are more particularly preferred:

In a most preferred embodiment, the compound according to the present invention is the following:

All of the above compounds can be obtained by a chemical process known to those skilled in the art, using commercially available reagents.

The thiopyridinone compound (1) can be prepared according to the method described, for example, in EP-A-3390363 or WO 2017/102349, which is incorporated herein by reference.

The thiopyridinone compound (1) can be an active ingredient or an active compound in cosmetic or dermatological products. The term “active” principle or compound used herein means an ingredient or compound that has an active cosmetic or dermatological property, such as anti-oxidant, whitening, UV filtration and anti-bacterial effects. The thiopyridinone compound (1) used in the present invention can function as a depigmentation, bleaching or bleaching agent, and thus the composition according to the present invention can be used as a bleaching product or as a cosmetic composition for whitening hair. a keratinous material.

The thiopyridinone compound (1) can be used as an agent for depigmenting, bleaching or whitening skin, body hair, eyelashes or hair, and also lips and/or nails, and preferably skin, particularly for eliminate pigmentation spots or senescence spots, and/or as an anti-tanning agent.

The amount of the thiopyridinone compound(s) (1) in the composition according to the present invention may be 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.

Furthermore, the quantity of the thiopyridinone compound(s) (1) in the composition according to the present invention may be 10% by weight or less, preferably 5% by weight or less, and more preferably 3% by weight. weight or less, relative to the total weight of the composition.

The quantity of the thiopyridinone compound(s) (1) in the composition according to the present invention may range from 0.01% to 10% by weight, preferably from 0.05% to 5% by weight, more preferably from 0 .1% to 3% by weight, relative to the total weight of the composition.

(Chelation agent)

The composition according to the present invention comprises (2) at least one chelating agent. Two or more chelating agents may be used in combination. Thus, a single type of chelating agent or a combination of different types of chelating agents can be used.

The chelating agent (2) may be an organic or inorganic chelating agent. It may be preferable that the chelating agent (2) is chosen from organic chelating agents.

The chelating agent (2) can be chosen from carboxylic acids, preferably aminocarboxylic acids, hydroxycarboxylic acids (hydroxy acids), phosphonic acids, preferably aminophosphonic acids, polyphosphoric acids, preferably linear polyphosphoric acids, and their salts. The salts may be, for example, alkali metal salts, alkaline earth metal salts or ammonium and substituted ammonium salts.

As a chelating agent (2), we can cite:

(i) aminocarboxylic acids and their salts, such as compounds with the following INCI name: diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and their salts such as EDTA 2Na and EDTA 4Na, ethylenediamine-N,N'- acid diglutaric acid (EDDG), glycinamide-N,N'-disuccinic acid (GADS), 2-hydroxypropylenediamine-N,N'-disuccinic acid (HPDDS), ethylenediamine-N,N'-bis(ortho-hydroxyphenylacetic) acid (EDDHA) , N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED), nitrilotriacetic acid (NTA), methylglycine diacetic acid (MGDA), N-2-hydroxyethyl-N,N-diacetic acid and glyceryl imino diacetic acid (as described in documents EP-A-317 542 and EP-A-399 133), iminodiacetic acid-N-2-hydroxypropyl sulfonic acid and aspartic acid N-carboxymethyl N-2-hydroxypropyl acid- 3-sulfonic acid (as described in EP-A-516,102), beta-alanine-N,N'-diacetic acid, aspartic acid-N,N'-diacetic acid and aspartic acid-N-monoacetic acid (described in EP -A-509 382), chelating agents based on iminodisuccinic acid (IDSA) (as described in EP-A-509 382), ethanoldiglycinic acid, phosphonobutane tricarboxylic acid, such as the compound marketed by Bayer under the reference Bayhibit AM, tetrasodium glutamate diacetate (GLDA) such as Dissolvine GL38 or 45S from Akzo Nobel;

(ii) hydroxycarboxylic acids and their salts, such as citric acid and its salts, for example, sodium citrate, in particular disodium citrate;

(iii) chelating agents based on mono- or polyphosphonic acids and their salts, such as compounds with the following INCI name: diethylenetriaminepenta(methylenephosphonic) acid (DTPMP), 1,1,2-ethane-hydroxy acid -triphosphonic acid (E1HTP), ethane-2-hydroxy-1,1,2-triphosphonic acid (E2HTP), ethane-1-hydroxy-1,1-diphosphonic acid (EHDP), ethane-1,1,2-triphosphonic acid (ETP), ethylenediaminetetramethylenephosphonic acid (EDTMP) and hydroxyethane-1,1-diphosphonic acid (HEDP), their salts and their derivatives, and

(iv) chelating agents based on polyphosphoric acid and their salts, such as compounds with the following INCI name: sodium tripolyphosphate (STP), tetrasodium diphosphate, hexametaphosphoric acid, sodium metaphosphate, phytic acid, their salts and their derivatives ,

And

their mixtures.

It may be preferable that the chelating agent (2) is selected from aminocarboxylic acids and their salts, hydroxycarboxylic acids and their salts, and more preferably from aminocarboxylic acids and their salts.

It may be more preferable that the chelating agent (2) is selected from the group consisting of EDTA and its salts (e.g., EDTA 2Na and EDTA 4Na), citric acid and its salts (e.g., citrate of sodium), N,N-bis(carboxymethyl)-L-glutamic acid and its salts (tetrasodium diacetate glutamate), metaphosphates (e.g., sodium metaphosphate), and mixtures thereof.

However, depending on the cases, the composition according to the invention may not include EDTA or salts thereof (for example, EDTA 2NA and EDTA 4Na).

The chelating agent (2) may not be ethylenediaminedisuccinic acid (EDDS) or salts thereof such as trisodium ethylenediamine disuccinate. Thus, it may be preferable that the composition according to the present invention does not include EDDS or salts thereof such as trisodium ethylenediamine disuccinate.

The amount of the chelating agent(s) (2) in the composition according to the present invention may be 0.01% by weight or more, preferably 0.05% by weight or more, and more preferably , 0.1% by weight or more, in particular, 0.2% by weight or more, relative to the total weight of the composition.

Furthermore, the quantity of the chelating agent(s) (2) in the composition according to the present invention may be 3% by weight or less, preferably 2% by weight or less, and more preferably 1% by weight or less, in particular 0.4% by weight or less, relative to the total weight of the composition.

The quantity of the chelating agent(s) (2) in the composition according to the present invention may be from 0.01% to 3% by weight, preferably from 0.05% to 2% by weight, plus preferably from 0.1% to 1% by weight, in particular from 0.2% to 0.4% by weight, relative to the total weight of the composition.

The weight ratio of the quantity of the thiopyridinone compound(s) (1) to the quantity of the chelating agent(s) (2), in the composition according to the present invention, can be 0.5 or more, preferably 1.0 or more, and more preferably 1.5 or more.

Furthermore, the weight ratio of the quantity of the thiopyridinone compound(s) (1) to the quantity of the chelating agent(s) (2), in the composition according to the present invention, can be 4 or less, preferably 3 or less, and more preferably 2 or less.

The weight ratio of the quantity of the thiopyridinone compound(s) (1) to the quantity of the chelating agent(s) (2), in the composition according to the present invention, can range from 0.5 to 4, preferably 1.0 to 3, and more preferably 1.5 to 2.

(pH correction agent)

The composition according to the present invention may comprise (3) at least one pH correction agent (pH corrector). Two or more pH correction agents may 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.

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

The acidifying agent may be a monovalent or multivalent acid, such as divalent.

The acidifying agents can 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 and lactic acid, as well as sulfonic acids.

The basifying agent may be a monovalent or multivalent base, such as divalent.

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

The mineral basifying agents can 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 their mixtures.

The organic basifying agents can 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 corresponding pKb to the function of greater basicity. In addition, organic amines do not include any fatty alkyl or alkenyl chains comprising more than ten carbon atoms.

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

(III)

in which

W represents a divalent C ₁ -C ₆ alkylene radical optionally substituted by one or more hydroxyl groups or a C ₁ -C ₆ alkyl radical, and optionally interrupted by one or more heteroatoms such as O and N, and

R _x , R _y , R _z and R _t , which may be the same or different, represent a hydrogen atom or a C ₁ -C ₆ alkyl, C ₁ -C ₆ hydroxyalkyl, or C ₁ -aminoalkyl radical. _C6 .

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

The term “alkanolamine” designates an organic amine comprising a primary, secondary or tertiary amine function, and one or more linear or branched C ₁ -C ₈ alkyl groups carrying one or more hydroxyl radicals.

Alkanolamines such as monoalkanolamines, dialkanolamines or trialkanolamines comprising one to three identical or different C ₁ -C ₄ hydroxyalkyl radicals may be suitable for the present invention. Compounds of this type include 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.

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. Amino acids can be in neutral or ionic form.

As amino acids which can be used in the present invention, mention may be made in particular of 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.

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.

Such basic amino acids can preferably be chosen from those corresponding to formula (IV) below:

(IV)

in which

R represents a group chosen from:

,

-(CH ₂ ) ₃ -NH ₂ ,

-(CH ₂ ) ₂ -NH ₂ ,

-(CH ₂ ) ₂ -NH-CO-NH ₂ , and

.

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

The organic basifying agent can be chosen from organic amines of heterocyclic type. In addition to histidine which has already been mentioned in the amino acids, we can cite in particular pyridine, piperidine, imidazole, triazole, tetrazole and benzimidazole.

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

The organic basifying agent can also be chosen from compounds comprising a guanidine function. As amines of this type which can 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-diethyl-guanidine, glycocyamine. , metformin, agmatine, N-amidinoalanine, 3-guanidino-propionic acid, 4-guanidinobutyric acid and 2-([amino(imino)methyl]amino)ethane-1-sulfonic acid.

In a preferred embodiment of the present invention, the organic basifying agent can 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 can be arginine.

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

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

The pH correction agent (3) may be present in an amount of 15 wt% or less, preferably 10 wt% or less, and more preferably 5 wt% or less, based on the total weight. of the composition.

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. % by weight or less, relative to the total weight of the composition.

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

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.

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.

The pH of the composition means the pH of the aqueous phase of the composition according to the present invention. pH can be measured according to JIS Z 8802 (2011).

It may be preferable that at least one buffer or buffering agent is also used, as pH correction agent (3), 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.

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

(Water)

The composition according to the present invention may comprise (4) water.

The amount of water (4) in the composition according to the present invention may be 30% by weight or more, preferably 35% by weight or more, and more preferably 40% by weight or more, relative to the total weight of the composition.

Furthermore, the quantity of water (4) in the composition according to the present invention may be 99% by weight or less, preferably 95% by weight or less, and more preferably 90% by weight or less, relative to the total weight of the composition.

The quantity of water (4) in the composition according to the present invention can be from 30% to 99% by weight, preferably from 35% to 95% by weight, and more preferably from 40% to 90% by weight, for example relative to the total weight of the composition.

(Other optional additives)

The composition according to the present invention may also comprise any other optional additive(s) usually used in the field of cosmetics, chosen, for example, from solvents, antioxidants, agents cosmetic active ingredients other than ingredient (1), such as oils, preservatives, and mixtures thereof.

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

As for the solvents, one or more cosmetically acceptable organic solvents may be cited, which may be alcohols: in particular monovalent alcohols such as ethyl alcohol, isopropyl alcohol, benzyl alcohol and phenylethyl alcohol; diols such as ethylene glycol, propylene glycol and butylene glycol; other polyols such as glycerol, sugar and carbohydrate alcohols; and ethers such as ethylene glycol monomethyl, monoethyl and monobutyl ethers, propylene glycol monomethyl, monoethyl and monobutyl ether, and butylene glycol monomethyl, monoethyl and monobutyl ethers.

The organic solvent(s) may be present in a concentration of 0.01% to 30% by weight, preferably 0.1% to 20% by weight, and more preferably from 1% to 10% by weight, relative to the total weight of the composition.

[Preparation]

The composition according to the present invention can be prepared by mixing the essential and optional ingredients described above in a conventional manner.

For example, the composition according to the present invention can be prepared by a process comprising the steps of mixing

(1) at least one thiopyridinone compound; And

(2) at least one chelating agent.

It is possible to additionally mix any of the optional ingredients.

Mixing can be carried out at any temperature such as room temperature (for example, at 20-25°C, preferably at 25°C), preferably at a temperature of 30°C or more, preferably 40°C. °C or more, and more preferably 50°C or more. It is preferable to further mix with any of the optional ingredients described above, such as a pH correction agent.

The form of the composition according to the present invention is not limited in particular, and can take various forms such as a W/O emulsion, an O/W emulsion, a gel, a solution, or the like. It is preferable that the composition according to the present invention is in the form of an emulsion, preferably an O/W emulsion, and more preferably an O/W gel emulsion.

[Cosmetic process]

The composition according to the present invention can be used as a cosmetic or dermatological composition, preferably as a cosmetic composition, and more preferably as a cosmetic composition for a keratinous material. As keratinous material, we can cite the skin, the scalp, the hair, the mucous membranes such as the lips, and the nails.

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

The composition according to the present invention may preferably be intended for application to a keratinous material such as the skin, the scalp and/or the lips, preferably the skin.

Thus, the composition according to the present invention can be used for a cosmetic process for a keratinous material, preferably the skin. In one embodiment, the present invention relates to a cosmetic process, preferably a bleaching process, for a keratinous material, preferably the skin, comprising the step of applying to the keratinous material the composition according to the present invention.

The composition according to the present invention can be used as a topical cosmetic composition in the form of a lotion, a milky lotion, a cream, a gel, a paste, a serum, 'a foam or a spray.

[Use]

The present invention also relates to a use of (2) at least one chelating agent in a composition comprising (1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I') below. below, their salts, solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures:

(I)

(I’)

in which

R ₁ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ , and

ii) -SR ₃ ,

And

R ₂ designates a radical chosen from

a) a hydrogen atom,

b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from

i) -OR ₃ ,

ii) -SR ₃ ,

iii) -C(O)-OR ₃ , and

iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and

c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals

in which

R ₃ designates a radical chosen from

a) a hydrogen atom, and

b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group

in order to stabilize the compound(s) (1).

The term “stabilize” has the same meaning as strengthening stability.

The use according to the present invention can increase the stability of the thiopyridinone compound (1) in the composition comprising it.

Therefore, the use according to the present invention can make it possible to store a composition comprising the thiopyridinone compound (1) for a long period of time, and in particular even under hot conditions.

The above explanations relating to the thiopyridinone compound (1) and the chelating agent (2) for the compositions according to the present invention can also be applied to those used in the use according to the present invention.

The composition in use according to the present invention may include any of the optional ingredients as explained above for the compositions according to the present invention.

EXAMPLES

The present invention will be described in more detail using examples. However, these examples should not be interpreted as limiting the scope of the present invention.

[Examples 1-5 and comparative example 1]

[Preparation]

Each of the compositions according to Examples 1 to 5 and Comparative Example 1 was prepared by mixing the ingredients listed in Table 1. The numerical values for the quantities of the ingredients are all based on "% by weight" as materials active.

Ingredients Example 1 Example 2 Example 3 Example 4 Example 5 Ex.
comp. 1 Water qsp100 qsp100 qsp100 qsp100 qsp100 qsp100 Glycerin 3 3 3 3 3 3 Butylene glycol 2.5 2.5 2.5 2.5 2.5 2.5 Conservatives 0.7 0.7 0.7 0.7 0.7 0.7 N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine 0.5 0.5 0.5 0.5 0.5 0.5 Disodium EDTA 0.3 0.2 0.4 - - - Sodium citrate - - - 0.3 - - Tetrasodium Glutamate Diacetate - - - - 0.3 - Potassium hydroxide 0.41 0.40 0.39 0.27 0.30 0.34 C13-16 isoparaffin 2 2 2 2 2 2 Thickeners 0.75 0.75 0.75 0.75 0.75 0.75 Dilauramidoglutamide lysine sodium 0.4 0.4 0.4 0.4 0.4 0.4 UV filters 25 25 25 25 25 25 Butyrospermum Parkii (shea) butter 1 1 1 1 1 1 Sorbitan oleate 0.5 0.5 0.5 0.5 0.5 0.5 Poly (C10-30 alkyl acrylate) 0.5 0.5 0.5 0.5 0.5 0.5

N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine (2-MERCAPTONICOTINOYL GLYCINE): Compound 20

[Ratings]

(pH)

The pH at 25ºC of each of the compositions according to Examples 1 to 5 and Comparative Example 1 was measured as follows.

Equipment :

1. pH meter; Laqua F-71 (Horiba)

2. pH electrodes; 9615S-10D (Horiba)

3. pH standard solutions (Horiba)

4. Internal pH probe solution (Horiba)

Procedures:

1. The internal solution introduction ports of the pH meter have been opened, and internal solutions have been brought around the electrodes.

2. Calibration was carried out using standard solutions at pH 9, 7 and 4.

3. The electrodes were washed with deionized water.

4. The protective cap of one of the electrodes (glass electrode) was removed, and the electrodes were immersed in each of the compositions according to Examples 1 to 5 and Comparative Example 1.

5. The pH was recorded after the pH value was stabilized.

The results are presented in the “pH” line of Table 2.

(Remaining level of thiopyridinone compound)

The amount of thiopyridinone compound in each of the compositions according to Examples 1 to 5 and Comparative Example 1 was measured by an HPLC-UV assay at the following time.

Moment (1) Just after preparation of the composition (T0)

Time (2) 2 weeks after preparation, where the composition was kept in a sealed container and protected from light at 55ºC

The details of the HPLC-UV assay are as follows.

Apparatus/Reagents HPLC system Ultra Performance LC (UPLC) HPLC column RP18, 1.7μm, 2.1mm x 100mm Eluent A Phosphoric acid 0.1% in water Eluent B Methanol

HPLC conditions UV detector 296nm Temp. column 30ºC Speed 0.4 mL/min Injection volume 1 μL Mobile phase Gradient mode
A: Phosphoric acid 0.1% in water
B: Methanol

The remaining level of thiopyridinone compound was determined by the following equation:

Remaining level of thiopyridinone compound (%) =

Amount of thiopyridinone compound at the moment (2)/Amount of thiopyridinone compound at the moment (1)

The results are presented in the line “Remaining level of thiopyridinone compound (%)” in Table 2 below.

The remaining level of thiopyridinone compound was also classified according to the following criteria:

Very good: 90% or more

Good: more than 85% to less than 90%

Bad: 85% or less

The results are presented in the “Stability” row in Table 2 below.

Example 1 Example 2 Example 3 Example 4 Example 5 Ex.
comp. 1 pH 5.8 5.8 5.8 5.8 5.8 5.8 Remaining level of thiopyridinone compound (%) 96 96 96 89 93 85 Stability Very good Very good Very good Good Very good Bad

(Results)

The compositions according to Examples 1 to 5, each of which included a thiopyridinone compound and a variety of chelating agents, were more stable, even at elevated temperature, such that a greater amount of the thiopyridinone compound remained than the composition according to comparative example 1 which did not include a chelating agent.

Claims (10)

Composition, preferably cosmetic composition, comprising
(1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I') below, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures:

(I)

(I')
in which
R ₁ designates a radical chosen from
a) a hydrogen atom, and
b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from
i) -OR ₃ , and
ii) -SR ₃ ,
And
R ₂ designates a radical chosen from
a) a hydrogen atom,
b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group optionally substituted by one or more groups, which may be identical or different, chosen from
i) -OR ₃ ,
ii) -SR ₃ ,
iii) -C(O)-OR ₃ , and
iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and
c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals
in which
R ₃ designates a radical chosen from
a) a hydrogen atom, and
b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group;
And
(2) at least one chelating agent. Composition according to claim 1, in which:
R ₁ of formulas (I) and (I') represents a hydrogen atom;
Or
R ₁ of formulas (I) and (I') represents a linear (C ₁ -C ₁₀ ) or branched (C ₃ -C ₁₀ ) alkyl group, in particular a linear alkyl group (C ₁ -C ₆ ) or branched (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, in particular said alkyl group of R ₁ is not substituted. Composition according to claim 1 or 2, in which:
R ₂ of formulas (I) and (I') represents a hydrogen atom;
Or
R ₂ of formulas (I) and (I') represents a linear (C ₁ -C ₁₀ ) or branched (C ₃ -C ₁₀ ) alkyl group, in particular a linear alkyl group (C ₁ -C ₆ ) or branched (C ₃ -C ₆ ), such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; said alkyl group of R ₂ not being substituted. Composition according to claim 1 or 2, in which:
R ₂ of formulas (I) and (I') represents a linear alkyl group (in C ₁ -C ₁₀ ) or a branched alkyl group (in C ₃ -C ₁₀ ), in particular a linear alkyl group (in C ₁ -C ₆ ) or a branched alkyl group (C ₃ -C ₆ ), 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 above, preferably said alkyl group being substituted by one or two groups chosen from i), ii) and iii), more preferably by one or two groups chosen from i) and iii), better substituted by a group iii) such as carboxy. Composition according to claim 1 or 2, in which:
R ₂ of formulas (I) and (I') represents a cycloalkyl group (C ₃ -C ₈ ), preferably a cycloalkyl group (C ₅ -C ₇ ) such as cyclohexyl;
Or
R ₂ of formulas (I) and (I') represents a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, preferably a phenyl group in particular unsubstituted. Composition according to any one of claims 1 to 5, in which:
R ₃ of formulas (I) and (I') represents a hydrogen atom;
Or
R ₃ of formulas (I) and (I') represents a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group; in particular a linear alkyl group (in C ₁ -C ₆ ) or a branched alkyl group (in C ₃ -C ₆ ), preferably an alkyl group (in C ₁ -C ₄ ) such as a methyl group. Composition according to any one of claims 1 to 6, in which:
R₁of formulas (I) and (I’) represents a radical chosen from
a) a hydrogen atom, and
b) a linear saturated C alkyl group₁-VS₆or in C₃-VS₆branched optionally substituted by one or more groups, which may be the same or different, chosen from
i) -O-R₃, And
ii) -S-R₃,
preferably optionally substituted with one or more groups i);
R₂of formulas (I) and (I’) represents a radical chosen from
a) a hydrogen atom, and
b) a linear saturated hydrocarbon group in C₁-VS₁₀or branched in C₃-VS₁₀or cyclic in C₃-VS₈such than in C₅-VS₆, optionally substituted by one or more groups, which may be identical or different, chosen from
i) -O-R₃,
ii) -S-R₃,
iii) -C(O)-O-R₃, And
iv) a phenyl group optionally substituted by one or more hydroxyls and/or by one or more C-alkoxy radicals₁-VS₄such as methoxy,
preferably substituted by one or more groups chosen from i) and iii), preferably iii) such as carboxy; And
R₃of formulas (I) and (I’) represents a radical chosen from
a) a hydrogen atom, and
b) a linear saturated C alkyl group₁-VS₆or branched in C₃-VS₆,
preferentially, the compounds of formula (I) and the tautomer (I’), their salts, solvates, such as hydrates, their optical isomers, their racemates, and their mixtures, have the following meanings:
R₁of formulas (I) and (I’) represents a radical chosen from:
a) a hydrogen atom, and
b) a linear saturated C alkyl group₁-VS₄or in C₃-VS₄branched optionally substituted by one or more groups, which may be the same or different, chosen from i) -OR_3,more preferably unsubstituted;
R₂of formulas (I) and (I’) represents a radical chosen from
a) a hydrogen atom, and
b) a linear saturated hydrocarbon group in C₁-VS₁₀or branched in C₃-VS₁₀or cyclic in C₃-VS₈such as in C₅-VS₆, optionally substituted by one or more groups, which may be identical or different, chosen from
i) -O-R₃,
iii) -C(O)-O-R₃, And
iv) an aryl group in C₅-VS₁₂optionally substituted by one or more hydroxyls and/or by one or more C-alkoxy radicals₁-VS₄; And
R₃of formulas (I) and (I’) represents a radical chosen from:
a) a hydrogen atom;
b) a linear saturated C alkyl group₁-VS₄or branched in C₃-VS₄such as methyl or ethyl. Composition according to any one of claims 1 to 7, in which:
the compound (1) is chosen from compounds 1 to 24 below, their tautomers, their salts, their solvates, such as their hydrates, their optical isomers, their racemates, and their mixtures, 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, and more preferably 20:



Cosmetic process, preferably whitening process, for a keratinous material, preferably skin, comprising the step:
application to the keratinous material of the composition according to any one of claims 1 to 8. Use of (2) at least one chelating agent in a composition comprising (1) at least one compound chosen from the compounds of formula (I) below, the tautomers of formula (I') below, their salts, their solvates, such as their hydrates, optical isomers, racemates and mixtures:

(I)

(I')
in which
R ₁ designates a radical chosen from
a) a hydrogen atom, and
b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group optionally substituted by one or more groups, which may be identical or different, chosen from
i) -OR ₃ , and
ii) -SR ₃ ,
And
R ₂ designates a radical chosen from
a) a hydrogen atom,
b) a linear C ₁ -C ₁₂ or branched C ₃ -C ₁₂ or cyclic C ₃ -C ₈ saturated hydrocarbon group, optionally substituted by one or more groups, which may be identical or different, chosen from
i) -OR ₃ ,
ii) -SR ₃ ,
iii) -C(O)-OR ₃ , and
iv) a C ₅ -C ₁₂ aryl group optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals, and
c) a C ₅ -C ₁₂ aryl group, optionally substituted by one or more hydroxyls and/or by one or more C ₁ -C ₈ alkoxy radicals
in which
R ₃ designates a radical chosen from
a) a hydrogen atom, and
b) a saturated linear C ₁ -C ₁₀ or branched C ₃ -C ₁₀ alkyl group
in order to stabilize the compound(s) (1).