WO2023245461A1

WO2023245461A1 - Composition for delivery of active compound

Info

Publication number: WO2023245461A1
Application number: PCT/CN2022/100263
Authority: WO
Inventors: Huiqin CHEN; Xiaomin WENG; Chunyan He; Yang Liu
Original assignee: L'oreal
Priority date: 2022-06-21
Filing date: 2022-06-21
Publication date: 2023-12-28
Also published as: FR3136660A1

Abstract

Disclosed is a composition comprising A) a thiopyridinone compound; B) a C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound, having at most one C=C bond.

Description

[Title established by the ISA under Rule 37.2] COMPOSITION FOR DELIVERY OF ACTIVE COMPOUND

TECHNICAL FIELD

The present invention relates to a composition for boosting delivery of active compounds into skin.

BACKGROUND

Care of skin, e.g., brightening of the skin, is always high interest of the consumers. Accordingly, it has always been an ultimate goal of the cosmetic filed to deliver to the consumers’ highly efficient products with skin benefits such as hydration, moisturizing, brightening, cleansing, and so on.

For efficient delivery, various forms of products are utilized. Up to date, it is still sometimes hard for hydrophilic actives to be delivered to deep skin (round dermis-junction) . In particular, it is known that certain thiopyridinone compounds exhibit good depigmenting activity, even at low concentration, see for example WO2012080075 and WO2017/102349. The thiopyridinone compound can show strong depigmenting or brightening effects by reducing the production of melanin.

There is therefore a need for a composition for boosting delivery of active compounds, e.g., thiopyridinone compounds, into skin.

SUMMARY OF THE INVENTION

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

In which Formulas (I) and (I’) :

R ₁ denotes a radical chosen from:

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R _3;

R ₂denotes a radical chosen from:

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R ₃

iii) -C (O) -O-R ₃;

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

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

R ₃ denotes a radical chosen from:

a) a hydrogen atom;

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

The compound (I’) is the tautomer form of the compound (I) when a tautomeric equilibrium exists according to the following scheme:

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

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

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

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

According to another embodiment of the invention R ₂ represents a linear (C ₁-C ₁₀) alkyl group or branched (C ₃-C ₁₀) alkyl group, especially a linear (C ₁-C ₆) alkyl group or branched (C ₃-C ₆) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; the said alkyl group being substituted by one or more groups selected from i) , ii) , iii) and iv) as defined herein before. Preferably the said alkyl group being substituted by one or two groups selected from i) , ii) and iii) , more preferably by one or two groups selected from i) and iii) , better substituted by one group iii) as carboxy.

Another variant for radical R ₂ is that the said alkyl group being substituted by one group iv) especially substituted by one phenyl group.

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

According to another embodiment of the invention R ₂ represents C ₅-C ₁₂ aryl group optionally substituted with one or more hydroxyls and/or with one or more C ₁-C ₈ alkoxy radicals, preferably a phenyl group particularly not substituted.

According to an embodiment R ₃ represents a hydrogen atom.

According to another embodiment R ₃ represents a saturated linear C ₁-C ₁₀ or 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, preferably (C ₁-C ₄) alkyl group such as methyl group.

DESCRIPTION OF DRAWINGS

Fig. 1 shows the distribution of compound 20 in test samples of Ex. 1 and some others;

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

Fig. 3 shows the distribution of compound 20 in test samples of Ex. 10-11 and CE. 3 via Raman confocal microscope; and

Fig. 4 shows the distribution of TXA in test samples of Ex. 10-11 and CE. 3 via Raman confocal microscope.

EMBODIMENTS OF INVENTION

Throughout the description, including the claims, the term "comprising a" should be understood as being synonymous with "comprising at least one" , unless otherwise mentioned. Moreover, the expression "at least one" used in the present description is equivalent to the expression "one or more" .

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

a“saturated hydrocarbonated group linear C ₁-C ₁₂ or branched C ₃-C _12” is equivalent to a “linear (C ₁-C ₁₂) alkyl or branched (C ₃-C ₁₂) alkyl group” which correspond to a saturated C ₁-C ₁₂ linear or branched C ₃-C ₁₂ hydrocarbon based group, and preferably C ₁-C ₁₀ linear or C ₃-C ₁₀ branched hydrocarbon based group, more preferably C ₁-C ₆ linear or C ₃-C ₆ branched hydrocarbon-based; Preferentially, the linear or branched groups may be chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl.

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

■ a saturated hydrocarbonated cyclic C ₃-C ₈ group is a mono or bicyclic cycloalkyl group containing from 3 to 8 carbon atoms especially is a monocyclic cycloalkyl group in C5 to C7 such as cyclohexyl group,

■ an "alkoxy radical" is an alkyl-oxy radical for which the alkyl radical is a linear or branched C ₁-C ₁₆ and preferentially C ₁-C ₈ hydrocarbon-based radical;

■ when the alkoxy group is optionally substituted, this implies that the alkyl group is optionally substituted as defined hereinabove;

■ an "aryl" group represents a fused or non-fused monocyclic or bicyclic carbon-based group comprising from 5 to 12 carbon atoms, preferably from 6 to 10 carbon atoms, and in which at least one ring is aromatic; preferentially, the aryl radical is a phenyl, biphenyl, naphthyl, more preferably a phenyl group;

■ the term "at least one" is equivalent to the term "one or more" ; and

■ the term "inclusive" for a range of concentrations means that the limits of that range are included in the defined range.

The salts of the compounds of formula (I) , (I’) , (II) or (II’) as defined herein after comprise the conventional non-toxic salts of said compounds, such as those formed from organic or inorganic acid or from organic or inorganic base.

As salts of the compounds of formula (I) , (I’) , (II) or (II’) mention may be made of:

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, potassium or calcium carbonate or hydrogen carbonate 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.

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

■ as "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 ₂SO ₄, iv) alkylsulfonic acids: Alk-S (O) ₂OH such as methanesulfonic acid and ethanesulfonic acid; v) arylsulfonic acids: Ar-S (O) ₂OH such as benzenesulfonic acid and toluenesulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid; x) alkoxysulfinic acids: Alk-O-S (O) OH such as methoxysulfinic acid and ethoxysulfinic acid; xi) aryloxysulfinic acids such as tolueneoxysulfinic acid and phenoxysulfinic acid; xii) phosphoric acid H ₃PO ₄; xiii) acetic acid CH ₃C (O) OH; xiv) triflic acid CF ₃SO ₃H; and xv) tetrafluoroboric acid HBF ₄;

■ The acceptable solvates of the compounds described in the present invention comprise conventional solvates such as those formed during the preparation of said compounds owing to the presence of solvents. Mention may be made, by way of example, of the solvates due to the presence ofwater or of linear or branched alcohols, such as ethanol or isopropanol.

■ The optical isomers are in particular, the enantiomers and the diastereoisomers.

Preferably, the “keratin material” according to the present invention is the skin. By “skin” , we intend all the body skin. Still preferably, the keratin material is the face, or the neck, especially the face.

In the application, unless specifically mentioned otherwise, amounts, contents, parts and percentages are expressed on a weight basis.

In the application, a numeric range is defined with a lower and an upper limit when needed, such as one or more lower limits and one or more upper limits are given to form a range optionally along with one or more preferred ranges. A given range can be defined by selecting a lower limit and an upper limit that define the boundaries of the given range. All ranges defined in this manner are inclusive and combinable, that is, any lower limit can be combined with any upper limit to form a range, as long as the lower and upper limits are provided to modify the same subject. For example, when ranges of 60-110 and 80-120 are listed for a specific subject, it is to be understood that ranges 60-120 and 80-110 are also contemplated and encompassed. Further, if the lower limits listed are 1 and 2 and the upper limits are listed as 3, 4 and 5, the following ranges are all predictable and within the scope of the present disclosure: 1-3, 1-4, 1-5, 2-3, 2-4 and 2-5.

Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of components and/or reaction conditions are to be understood as being modified in all instances by the term "about" , with conventionally known meaning in the art, e.g., within 10%of the indicated number (such as "about 10%" means 9%-11%and "about 2%" means 1.8%-2.2%) .

Component A)

The composition according to the invention comprises a compound of formula (I) or (I’) below or tautomer (I’) below or their salts, their optical isomers, racemates, and/or solvates such as hydrates and the thereof, alone or as a mixture, as component A) :

In which Formulas (I) and (I’) :

R ₁ denotes a radical chosen from:

a) a hydrogen atom;

i) -O-R ₃

ii) -S-R _3;

R ₂denotes a radical chosen from:

a) a hydrogen atom;

i) -O-R ₃

ii) -S-R ₃

iii) -C (O) -O-R ₃;

R ₃ denotes a radical chosen from:

a) a hydrogen atom;

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

According to an embodiment R ₃ represents a hydrogen atom.

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

have the following meanings:

R ₁ denotes a radical chosen from:

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R _3;

preferably optionally substituted with one or more groups i)

R ₂ denotes a radical chosen from:

a) a hydrogen atom;

b) a saturated hydrocarbonated group linear C ₁-C ₁₀ or branched C ₃-C ₁₀ or cyclic C ₃-C ₈ such as C5-C6, optionally substituted with one or more groups, which may be identical or different, chosen from:

i) -O-R ₃

ii) -SR- ₃

iii) -C (O) -O-R ₃;

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

preferably substituted with one or more groups selected from i) and iii) , preferably iii) such as carboxy

R ₃ denotes a radical chosen from:

a) a hydrogen atom;

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

Preferentially, the compounds of formula (I) and tautomer (I’) or their salts, their optical isomers, racemates, and/or solvates such as hydrates and the thereof, alone or as a mixture; have the following meanings:

R ₁ denotes a radical chosen from:

a) a hydrogen atom;

b) a saturated linear C ₁-C ₄ or branched C ₃-C ₄ alkyl group optionally substituted with one or more groups, which may be identical or different, chosen from i) -OR _3, more preferably not substituted;

R ₂ denotes a radical chosen from:

a) a hydrogen atom;

b) a saturated hydrocarbonated group linear C ₁-C ₁₀ or branched C ₃-C ₁₀ or cyclic C ₃-C ₈ as C5-C6, optionally substituted with one or more groups, which may be identical or different, chosen from:

i) -O-R ₃

iii) -C (O) -O-R ₃;

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

R ₃ denotes 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.

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

have the following meanings:

R ₁ is a hydrogen atom; and

R ₂ denotes a radical chosen from:

a) a hydrogen atom;

b) a saturated hydrocarbonated group linear C ₁-C ₅ or branched C ₃-C ₅ or cyclic C ₃-C ₈ as C5-C6, substituted with one or more groups, which may be identical or different, chosen from v) -C (O) -O-R ₃, preferably substituted with one group iii) -C (O) -O-R ₃;

R ₂ is even more preferably a saturated hydrocarbonated group linear C ₁-C ₄ or branched C ₃-C ₄ substituted with one group iii) -C (O) -OR ₃.

According to another preferred embodiment, compounds of formula (I) and tautomer (I’) are selected among compounds of formula (II) and also the tautomers thereof, the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture:

Formula (II) and (II’) Wherein R1 and R3 have the same meaning than for compounds of formula (I) and (I’) and X denotes an alkylene radical- (CH ₂) _n-with n being an integer ranging inclusively from 1 to 10, preferably ranging from 1 to 6, more preferably ranging from 1 to 4, such as 1, preferably R ₃ represents a hydrogen atom.

Among the compounds of formula (I) , the following compounds are preferably used and their tautomer or their salts, their optical isomers, racemates, and/or solvates such as hydrates and the thereof, alone or as a 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 compounds can be obtained by chemical method known by man skilled in the art, from commercially available reagents. For example, the synthetic method disclosed in the European patent application EP3 390 363 can be used.

The compound 20, N- [ (2-thioxo-1, 2-dihydropyridin-3-yl) carbonyl] glycine, may also be nominated as 3-carboxymethylaminocarbonyl-2-thiopyridinone, is a typical representative of the useful thiopyridinone compounds according to the present invention.

Solubility of Component A)

By deep study, the inventors believe, without being restricted by any known theory, that compound of formula (I) or (I’) , in particular e.g., compound 20, can be a typical representative of the useful thiopyridinone compounds according to the present invention thanks mainly to a specific log P thereof.

The term “log P” is a measurement known in the art to distinguish a "hydrophilic" and "hydrophobic" compound. The value of log P can be determined with any conventionally known method in the art. For the “log P” , P is a partition coefficient, representing the ratio of the equilibrium concentration of a compound in an organic phase to that in an aqueous phase. Usually, a value of P for a compound between octanol and water is used in the art. Consequently, a hydrophilic compound generally has a log P value less than 3.5, less than 1.0, or typically less than about-0.5, where P is the partition coefficient of the compound between octanol and water; and a hydrophobic compound generally has a log P of 3.5 or more, or typically 5.0 or more.

Based on compound 20, the inventors make broad study and determine that, compound 20 is particular useful mainly because it has a log P falling into the range of -1.6 to 0.5, preferably-0.5 to 0.2. Accordingly, the thiopyridinone compounds of formulae (I) or (I’) having a log P of from-1.6 to 0.5 are particularly preferred for use as component A) .

The component A) , e.g., compound (I) , (I’) , (II) and/or (II’) , especially one having a log P of from-1.6 to 0.5, may be present in an amount ranging for example from 0.01%to 10%by weight, preferably from 0.1%to 5%by weight, in particular from 0.5%to 3%by weight, relative to the total weight of the composition.

Component A’) , additional hydrophilic active compounds

As stated above, compound 20 is particular useful mainly because it has a log P falling into the range of-1.6 to 0.5. In other words, various cosmetically acceptable additional hydrophilic active compounds in the need of being delivered to skin can be used as component A’) according to the present invention or being used in combination with component A) ; as long as the additional hydrophilic active compound has a log P of from-1.6 to 0.5.

According to an embodiment of the invention, component A’) preferably bears a carboxyl group, in particular being a carboxylic acid or ester/salt thereof, preferably a carboxylic acid.

For example, amongst others, tranexamic acid (TXA) is a typical example of component A’) . According to an embodiment of the invention, TXA is used as component A’) together with compound 20 as component A) .

Further, water soluble vitamins can be used in the composition as an active compound of component A') . The useful examples of vitamin comprise vitamin C (ascorbic acid) , vitamin B group (e.g., vitamin B5 (panthenol) , vitamin B3 (niacinamide) , vitamin B1 and vitamin B2) , nicotinic acid, folic acid, pantothenic acid, the derivatives of these vitamins (in particular esters) and their mixtures.

The component A) , i.e., thiopyridinone compound of formula (I) or (I’) , is a derivative of niacinamide. For the purpose of the invention, other derivatives thereof known useful as active compounds for cosmetic use, especially for skin, can also be used.

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

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

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

The term “fatty compound” means organic compounds that are insoluble in water at ordinary temperature (25℃) and at atmospheric pressure (760 mmHg) (solubility of less than 5%, preferably 1%and even more preferentially 0.1%) . In addition, the fatty compounds are generally soluble in organic solvents under the same temperature and pressure conditions, for instance chloroform, ethanol, benzene or decamethylcyclo-pentasiloxane.

The fatty compounds are especially chosen from fatty alcohols, fatty acids, fatty acid esters, and/or fatty alcohol esters. According to an embodiment of the invention, the fatty compound of component B) according to the invention does not comprise additional hetero-atom other than C, H and O atoms.

According to the present invention, it is believed that use of the specific component B) in combination component A) and/or A') can promote the delivery of component A) and/or A') into skin. Without being limited with any known theory, it is deduced that an appropriate length of carbon chain is important for the delivery. A too long carbon chain may result in less effect of delivery, whilst a too short carbon chain may be too volatile to be formulated into a useful product. By studying the matching with component A) and/or A') and through experiments, it is believed that the useful component B) can be a C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound.

According to an embodiment of the invention, an exemplary component B) can bear a C1-C6 alkyl branch.

Meanwhile, it is surprised to see that for the purpose of the present invention, the useful fatty compound can preferably have at most one C=C double bond, e.g., having no C=C bond. Accordingly, a C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound, having a saturated carbon chain may be particularly useful.

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

The fatty acid that may be used in the composition of the invention includes C12-C16 fatty acid, such as lauric acid or lauroleic acid (C12) , myristic acid or myristelaidic acid (C14) , palmitic acid or palmitoleic acid (C16) .

The esters useful are esters of saturated or unsaturated, linear or branched aliphatic mono-or polyacids and of saturated or unsaturated, linear or branched aliphatic mono-or polyalcohols, as long as the total carbon number of the esters being 12 to 20.

Among the monoesters, mention may be made of cetyl lactate; C ₁₂-C ₁₅ alkyl lactate; lauryl lactate; oleyl lactate; octyl octanoate; isononyl isononanoate; octyl isononanoate; 2-ethylhexyl isononate; octyl pelargonate; ethyl and isopropyl palmitates, alkyl myristates such as butyl, myristate, laurate or ethyl oleate.

Among the polyesters, mention may be made of: diethyl sebacate; diisopropyl sebacate; diisopropyl adipate; di-n-propyl adipate; dioctyl maleate; glyceryl undecylenate; propylene glycol dicaprylate; triisopropyl citrate; glyceryl trilactate.

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

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

Component C) , surfactant

The composition according to the present invention can comprise a surfactant as an optional component C) , e.g., a nonionic surfactant, or a mixture thereof. According to the present invention, any conventional surfactant can be used, as long as it is compatible with other components of the composition, especially with components A) , A’) and/or B) , in particular those benefiting, or at least not adversely affecting, the effect of delivering component A) and/or A’) into skin.

Examples of the useful nonionic surfactants may comprise esters of polyols and of fatty acids with a saturated or unsaturated chain containing, and the oxyalkylenated derivatives thereof, i.e. derivatives containing oxyethylenated and/or oxypropylenated units, such as the glyceryl esters, and the oxyalkylenated derivatives thereof; the polyethylene glycol esters, and the oxyalkylenated derivatives thereof; the sorbitol esters, and the oxyalkylenated derivatives thereof; the sugar (sucrose, glucose or alkylglucose) esters, and the oxyalkylenated derivatives thereof; fatty alcohol ethers; the sugar ethers, and mixtures thereof.

Glyceryl esters of fatty acids that may especially be mentioned include glyceryl stearate (glyceryl monostearate, distearate and/or tristearate) .

Polyethylene glycol esters of fatty acids that may especially be mentioned include polyethylene glycol 40 OE monostearate (CTFA name: PEG-40 stearate) .

Mixtures of these surfactants may also be used.

Matching the solubility of component A) and the nature of component B) , as well as the medium/solvent to be used, the component C) , when being used, can preferably have a HLB value of 2-20, preferably 8-20, or preferably 10-18.

The nonionic surfactant may be present in the composition according to the present invention in an amount from 0.1%to 15%by weight, such as from 0.15%to 10%by weight, relative to the total weight of the composition.

Component D) , Medium/solvent

The composition according to the invention can advantageously comprise at least one medium/solvent, including water and/or organic medium/solvent, for use an optional component D) .

Water

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

For high viscosity applications of the composition, e.g., in form of leave-on cream, a relatively lower amount of water may be used. The high viscosity composition according to the invention advantageously comprises water in a content of less than or equal to 40%by weight relative to the total weight of composition. The water content in the high viscosity composition according to the invention preferably ranges from 10%to 40%by weight, more preferably from 15%to 35%by weight, or from 20%to 30%by weight, relative to the total weight of the composition.

Organic medium/solvent

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

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

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

The organic medium/solvents, when they are present in an amount ranging from 0.1%to 40%by weight, preferably from 1%to 30%by weight, or from 3%to 20%by weight, relative to the total weight of the composition according to the invention.

pH Adjusting Agent

The composition according to the present invention may comprise (3) at least one pH adjusting agent (pH adjuster) . Two or more pH adjusting agents may be used in combination. Thus, a single type of pH adjusting agent or a combination of different types of pH adjusting agents may be used.

As the (3) pH adjusting agent, at least one acidifying agent and/or at least one basifying agent (alkaline agent) may be used.

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

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 instance tartaric acid, citric acid, and lactic acid, as well as sulphonic acids.

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

The basifying agents may be mineral (inorganic) or organic, or hybrid.

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

The organic basifying agents may be chosen from organic amines with a pKb at 25℃ of less than 12, preferably less than 10, and even more advantageously less than 6. It should be noted that it is the pKb corresponding to the function of highest basicity. In addition, the organic amines do not comprise any alkyl or alkenyl fatty chains comprising more than ten carbon atoms.

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

in which

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

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

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

The term “alkanolamine” means an organic amine comprising a primary, secondary or tertiary amine function, and one or more linear or branched C ₁-C ₈ alkyl groups bearing 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. Among the compounds of this type, 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.

Amino acids that may 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 carboxylic acid, sulfonic acid, phosphonic acid or phosphoric acid functions. The amino acids may be in neutral or ionic form.

As amino acids that may be used in the present invention, mention may be made especially 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 an ureido function.

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

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

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

The organic basifying agent may be chosen from organic amines of heterocyclic type. Besides histidine that has already been mentioned in the amino acids, mention may in particular be made of pyridine, piperidine, imidazole, triazole, tetrazole and benzimidazole.

The organic basifying agent may also be chosen from amino acid dipeptides. As amino acid dipeptides that may be used in the present invention, mention may be made especially of carnosine, anserine and baleine.

The organic basifying agent may also be chosen from compounds comprising a guanidine function. As amines of this type that may be used in the present invention, besides arginine, which has already been mentioned as an amino acid, mention may be made especially 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 may be selected from amino acids, preferably basic amino acids, and more preferably arginine, lysine, histidine or mixtures thereof. Even more preferentially, the organic basifying agent may be arginine.

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

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

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

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

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

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

It is preferable that the composition according to the present invention have a pH of from 4.5 to 6.5, and more preferably from 5 to 6.

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

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

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

Adjuvants

In a known manner, the composition of the present invention may also contain adjuvants which are customary in the cosmetic, pharmaceutical and/or dermatological field depending on the final uses and/or the specific product forms, such as hydrophilic or lipophilic gelling agents, emulsifiers, hydrophilic or lipophilic active agents, preservatives, fragrances, fillers, pH adjusters, odor absorbers and dyes. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20%by weight of the total weight of the composition.

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

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

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

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

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

The subject of the invention is also a cosmetic process for the care or makeup of keratin materials, comprising the application to the keratin materials of a composition as defined above.

The subject of the invention is also a non-therapeutic cosmetic process for the care or makeup of keratin materials, comprising the application to the keratin materials of a composition as defined above.

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

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

In a particular embodiment, the composition is suitable for the treatment of darker and/or more coloured spots on the skin.

EXAMPLES

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

The ingredient amounts/concentrations in the compositions/formulas described below are expressed in %by weight, relative to the total weight of each composition/formula, unless otherwise indicated.

Main raw materials used, trade names and supplier thereof are listed below.

Compound 20 is synthesized as disclosed in example 2 of patent EP3 390 363.

Example A

The inventive compositions of Ex. 1-9, as well as comparative composition of CE. 1-2, were prepared, from the ingredients indicated in the table 1 below (in which the contents were indicated in%by weight of materials with regard to the total weight of the composition) :

Table 1

The compositions were prepared by the steps of, taking Ex. 1 as an example:

1) . Heating the fatty compounds to 75℃, mixing well till all solid melted.

2) . Mixing soluble raw materials, and heating to 75℃, mixing well till no lumps.

3) . Transferring oil phase into water phase at 75℃, mixing homogenously for 15mins.

4) . Cooling to 30℃.

5) . Finally adding compound 20 and adjusting pH to be 5.6±0.3.

Example B

The inventive compositions of Ex. 1-9, as well as comparative composition of CE. 1-2, prepared in Example A were evaluated via Raman spectroscopy and Bioavailability study.

Raman spectroscopy:

A LabRam HR Evolution (Horiba Jobin-Yvon, illeneuve-d'A scq, France) Raman confocal microscope was used. Raman spectrum was obtained using a 532 nm DPSS laser with a power of 8 mW on the sample, coupled with a×50 LM Plan (Olympus, NA 0.75, Rungis, France) objective. The confocal hole was set at 100μm diameter for all measurements. The system was spectrally calibrated to the 520.7 cm ^-1 spectral line of silicon before the test. Detection was facilitated by dispersing Raman-shifted radiation onto a charge-coupled device (CCD) detector using a grating of 600lines/mm.

For pure active ingredients, single point spectra were acquired with 25%laser intensity and 10 seconds acquisition time, for 400-2000cm ^-1 spectral range.

For mapping in formula test, the step size was 3μm in both X and Y direction. The acquisition areas were 18 X 150μm. For each spot, 50%laser intensity and 5 seconds acquisition time per spectrum was used. Spectral range was 400-2000cm ^-1.

For the test, skin tissue samples were prepared as follows: for the sample preparation, 6μl of formula was applied evenly on 0.8cm X 0.8cm porcine skin, corresponding to 9mg/cm ². The porcine skin sample was then emerged on insert membrane with PBS underneath, followed by 37℃ incubation at 95%RH for 6 hours. Treated sample was embedded in OCT, then frozen and cryo-sectioned into 20μm thickness. It was further placed on a CaF ₂ substrate for Raman confocal scanning. Three porcine samples were prepared for each formula. A Raman confocal mapping was acquired of each treated sample.

Bioavailability study:

For the percutaneous absorption study, vertical diffusion cells were used. The study was conducted by following the procedure: formula containing active of interest was applied to skin samples (n=9) at 5 mg/cm ². After 16 h exposure, unabsorbed residual remaining on skin surface was washed out, stratum corneum were then collected by tape stripping (20 trips, pooled by 10) , epidermis, dermis and receptor fluid were collected. Active were extracted from each of the compartments collected: washing, tape striping, epidermis, dermis and receptor fluid, and active amount was quantified with LC MS/MS. Mass balance was checked to see whether the applied amount of T on the skin was recovered at the end of experiment; data were excluded when the mass balance did not meet the criterion of 100±15%.

Table 2 Active delivery data in Bioavailability test–corresponding to table 1

√: signal can be observed in stratum corneum, epidermis; Δ: Sparse signal can be found in epidermis;

○: weak signal can be found in epidermis; and

×: no signal can be observed in skin

The results were also provided in Fig. 1 and Fig. 2. For compound 20, signals were observed in stratum corneum and epidermis in Ex. 1, Ex. 4, Ex. 5, Ex. 6, Ex. 7, Ex. 8 and Ex. 9 while there was no signal found in CE. 2. For TXA active, weak or sparse signals were found in epidermis in Ex. 2, Ex. 4, Ex. 6 and Ex. 7 while there was no signal found in CE. 1.

Table 3: Bioavailability data:

The bioavailability results were shown in Tab. 3. For the inventive examples, high%of applied dose in the skin in sample formulae, especially more than 1%active in (Epidermis+Dermis+RF) were obtained; while active was found less in the skin in CE. 1 and CE. 2.

Example C

The inventive compositions of Ex. 10-11, as well as comparative composition of CE. 3, were prepared, from the ingredients indicated in the table 2 below (in which the contents were indicated in%by weight of materials with regard to the total weight of the composition) :

Table 4

Components	Ex. 10	Ex. 11	CE. 3
PEG-40 STEARATE	1.2	1.2	1.2
SUCROSE TRISTEARATE	0.5	0.5	0.5
GLYCERIN	9	9	9
ETHYL OLEATE	1
HEXYLDECANOL		1
ETHYL LINOLEATE			3
TRANEXAMIC ACID	1	1	1
NIACINAMIDE	4	4	4
COMPOUND 20	0.5	0.5	0.5
WATER	Qs to 100	Qs to 100	Qs to 100

Example D

The inventive compositions of Ex. 10-11, as well as comparative composition of CE. 3, prepared in Example C were evaluated via Raman spectroscopy as stated in Example B.

The result was shown in Fig. 3. The three formulae are comparable in compound 20 signal intensity and depth in the porcine skin, all the signals can be observed in stratum corneum, epidermis and dermis.

The result was also shown in Fig. 4. For Ex. 10, TXA signal is evenly distributed in the stratum corneum, epidermis and dermis. But for Ex. 11&CE. 3, no obvious signal can be observed in epidermis, only observed in stratum corneum and dermis.

It is concluded that with the technical solutions of the present invention, using a fatty compound having at most one C=C bond, the formulae can achieve penetration of the active substance comparable with conventional ones having 2 or more C=C bonds, but inhibit or even avoid the defect of storage unstability brought by the more C=C bonds.

Claims

A composition comprising the components of:

A) at least one compound selected from compounds of formula (I) and tautomer of formula (I’) herein below; and their salts, optical isomers, racemates, and/or solvates such as hydrates, alone or as a mixture:

in which Formulas (I) and (I’) :

- R ₁ denotes a radical chosen from:

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R ₃;

- R ₂ denotes a radical chosen from:

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R ₃

iii) -C (O) -O-R ₃;

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

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

- R ₃ denotes a radical chosen from:

a) a hydrogen atom;

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

B) at least one C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound, having at most one C=C bond, with the proviso that when component B) is a fatty acid, it is a C12-C16 fatty acid.
The composition according to claim 1, wherein:

- 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) alkyl group or branched (C ₃-C ₁₀) alkyl group, especially a linear (C ₁-C ₆) alkyl group or branched (C ₃-C ₆) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, particularly the said alkyl group of R ₁ is not substituted.

-
The composition according to any one of the preceding claims, wherein:

- 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) alkyl group or branched (C ₃-C ₁₀) alkyl group, especially a linear (C ₁-C ₆) alkyl group or branched (C ₃-C ₆) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl group; the said alkyl group of R ₂ being not substituted.
The composition according to claim 1 or 2, wherein:

- R ₂ of formula (I) and (I’) represents a linear (C ₁-C ₁₀) alkyl group or branched (C ₃-C ₁₀) alkyl group, especially a linear (C ₁-C ₆) alkyl group or branched (C ₃-C ₆) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl; the said alkyl group being substituted by one or more groups selected from i) , ii) , iii) and iv) as defined in claim 1, preferably the said alkyl group being substituted by one or two groups selected from i) , ii) and iii) , more preferably by one or two groups selected from i) and iii) , better substituted by one group iii) as carboxy.
The composition according to claim 1 or 2, wherein

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

or

- R ₂ of formula (I) and (I’) represents a C ₅-C ₁₂ aryl group optionally substituted with one or more hydroxyls and/or with one or more C ₁-C ₈ alkoxy radicals, preferably a phenyl group particularly not substituted.
The composition according to any one of the preceding claims, wherein

- 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; particularly a linear (C ₁-C ₆) alkyl group or a branched (C ₃-C ₆) alkyl group, preferably (C ₁-C ₄) alkyl group such as methyl group.
The composition according to any one of the preceding claims, wherein:

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

a) a hydrogen atom;

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

i) -O-R ₃

ii) -S-R 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;

- b) a saturated hydrocarbonated group linear C ₁-C ₁₀ or branched C ₃-C ₁₀ or cyclic C ₃-C ₈ such as C5-C6, optionally substituted with one or more groups, which may be identical or different, chosen from:

- i) -O-R ₃

- ii) -SR- ₃

- iii) -C (O) -O-R ₃;

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

- preferably substituted with one or more groups selected from i) and iii) , preferably iii) such as carboxy

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

- a) a hydrogen atom;

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

- preferentially, the compounds of formula (I) and tautomer (I’) or their salts, their optical isomers, racemates, and/or solvates such as hydrates and the thereof, alone or as a mixture;

- have the following meanings:

- R ₁ 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 optionally substituted with one or more groups, which may be identical or different, chosen from i) -OR ₃, more preferably not substituted;

- R ₂ of formula (I) and (I’) represents a radical chosen from:

- a) a hydrogen atom;

- b) a saturated hydrocarbonated group linear C ₁-C ₁₀ or branched C ₃-C ₁₀ or cyclic C ₃-C ₈ as C5-C6, optionally substituted with one or more groups, which may be identical or different, chosen from:

- i) -O-R ₃

- iii) -C (O) -O-R ₃;

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

- 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.
The composition according to any one of the preceding claims, wherein

the compound of formula (I) selected out from the group consisting of the compounds 1 to 24 below and their tautomer or their salts, their optical isomers, racemates, and/or solvates such as hydrates, alone or as a mixture, particularly compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, or 21, more particularly 1, 9, 16, 18, 19, 20, or 21, preferably 18, 19, 20, or 21, more preferably 20:
The composition according to any one of the preceding claims, wherein the component A) is selected from those having a log P falling into the range of -1.6 to 0.5.
The composition according to any one of the preceding claims, wherein an additional hydrophilic active compound having a log P of from-1.6 to 0.5 is used as a component A’) in combination with component A) , the component A’) being preferably selected from the group consisting of water soluble vitamins, cosmetically acceptable derivatives of niacinamide, and tranexamic acid, preferably ascorbic acid, niacinamide or tranexamic acid.
The composition according to any one of the preceding claims, wherein the component A) and/or A') is present in an amount ranging from 0.01%to 20%by weight, preferably from 0.05%to 10%by weight, or preferably from 0.1%to 5%by weight, relative to the total weight of the composition.
The composition according to any one of the preceding claims, wherein the component B) is chosen from fatty alcohols, fatty acids, fatty acid esters, and/or fatty alcohol esters, especially from

lauryl alcohol, oleyl alcohol and the mixture thereof;

lauric acid or lauroleic acid (C12) , myristic acid or myristelaidic acid (C14) , palmitic acid or palmitoleic acid (C16) ;

cetyl lactate; C ₁₂-C ₁₅ alkyl lactate; lauryl lactate; oleyl lactate; octyl octanoate; isononyl isononanoate; octyl isononanoate; 2-ethylhexyl isononate; octyl pelargonate; ethyl and isopropyl palmitates, alkyl myristates such as butyl, myristate, laurate or ethyl oleate; and

diethyl sebacate; diisopropyl sebacate; diisopropyl adipate; di-n-propyl adipate; dioctyl maleate; glyceryl undecylenate; propylene glycol dicaprylate; triisopropyl citrate; glyceryl trilactate.
The composition according to any one of the preceding claims, further comprising a nonionic surfactant for use as component C) , chosen from esters having 21 or more carbon atoms of (poly) alcohols and of fatty acids with a saturated or unsaturated chain.
The composition according to claim 13, wherein the component C) has a HLB value of 2-20, preferably 8-20, or preferably 10-18.
The composition according to any one of the preceding claims, further comprising water and/or organic medium/solvent, for use component D) , the organic medium/solvent being preferably selected from the group consisting of linear or branched, monoalcohols or diols, comprising 2 to 10 carbon atoms; aromatic alcohols such as phenylethyl alcohol; polyols containing more than two hydroxyl functions, such as glycerol; polyol ethers, for instance ethylene glycol monomethyl, monoethyl and monobutyl ether, propylene glycol or ethers thereof, for instance propylene glycol monomethyl ether; and mixture thereof.
The composition according to any one of the preceding claims, wherein an organic medium/solvent comprised, preferably present in an amount ranging from 0.1%to 40%by weight, preferably from 1%to 30%by weight, or from 3%to 20%by weight, relative to the total weight of the composition.
Use of the combination of

component A) an active compound having a log P of from-1.6 to 0.5

component B) a C12-20 fatty compound, preferably a C12-C18 fatty compound, or preferably a C12-C16 fatty compound, having at most one C=C bond; and

optionally component C) ; a surfactant having a HLB value of 2-20, preferably 8-20, or preferably 10-18; and

optionally component D) a glycol having a log P of from-3.0 to 3.5, preferably-3.0 to 0.5,

for boosting delivery of the component A) into skin.
A non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, preferably skin, comprising the step of:

applying to the keratin substance the composition according to any one of claims 1 to 16.