Cosmetic composition comprising niacinamide and gingerol for the treatment of hair loss

Abstract

Cosmetic composition comprising niacinamide and a gingerol for the treatment of hair loss The present invention relates to a cosmetic composition comprising: - at least one compound of formula (I), - at least one gingerol, and - optionally at least one shogaol; in which the mass ratio [compound of formula (I) / gingerol] is less than or equal to 150, and when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1. The invention also relates to a cosmetic treatment method comprising at least one step of applying this composition to keratin materials. The invention also relates to the non-therapeutic cosmetic use of this combination of active agents for inducing and / or stimulating the growth of keratin fibers and / or slowing their loss and / or for treating alopecia, in particular androgenic alopecia. Figure for abstract: none

Description

Title of the invention: Cosmetic composition comprising niacinamide and gingerol for the treatment of hair loss

[0001] The present invention relates to the field of scalp and keratin fiber care, more particularly to the field of keratin fiber growth and prevention of hair loss.

[0002] The present invention relates to a cosmetic composition comprising:

[0003] - at least one compound of formula (I),

[0004] - at least one gingerol, and

[0005] - possibly at least one shogaol;

[0006] in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and

[0007] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1.

[0008] The invention also relates to a cosmetic treatment method comprising at least one step of applying this composition to keratin materials. The invention also relates to the non-therapeutic cosmetic use of this combination for inducing and / or stimulating the growth of keratin fibers and / or slowing their loss and / or for treating alopecia, in particular androgenic alopecia.

[0009] Hair growth and renewal are mainly determined by the activity of hair follicles and their matrix environment. Their activity is cyclical and essentially comprises three phases, namely the anagen phase, the catagen phase and the telogen phase.

[0010] The anagen phase (active or growth phase), which lasts several years and during which the hair grows, is followed by a very short and transient catagen phase which lasts a few weeks, then a telogen phase or resting phase which lasts a few months. At the end of the resting period, the hair falls out and another cycle begins. The hair is therefore constantly renewed and of the approximately 150,000 hairs in a head of hair, approximately 10% are at rest and will be replaced in the coming months. Natural hair loss or shedding can be estimated, on average, at a few hundred hairs per day for a normal physiological state. This process of permanent physical renewal undergoes a natural evolution during aging, the hair becomes finer and its cycles shorter. In addition, various causes can lead to significant, temporary or permanent hair loss. Hair loss, in particular alopecia, is essentially due to disruptions in hair renewal. These disruptions initially lead to an acceleration in the frequency of cycles to the detriment of hair quality, then of their quantity. There is a progressive miniaturization of the bulbs, with concomitant isolation of these by progressive thickening of the perifollicular collagen matrix as well as the external connective sheath. Revascularization around the hair follicle is therefore made more difficult cycle after cycle. The hair regresses, miniaturizing until it is nothing more than non-pigmented down and this phenomenon leads to a progressive impoverishment of the hair. It is in number and average diameter that the hair follicles that make up the hair are affected. Areas are preferentially affected, notably the temporal or frontal gulfs in men, and in women, there is diffuse alopecia of the vertex..

[0011] The term alopecia also covers a whole family of hair follicle disorders that ultimately result in permanent, partial or general hair loss. This is more specifically androgenic alopecia. In a significant number of cases, early hair loss occurs in genetically predisposed individuals; this is called andro-chronogenetic alopecia; this form of alopecia particularly affects men. It is also known that certain factors such as hormonal imbalance, physiological stress, malnutrition, can accentuate the phenomenon. In addition, hair loss or alteration may be related to seasonal phenomena.

[0012] Hair loss and hair loss are often felt as distressing by those affected, especially when they are still young.

[0013] Pharmacological active agents such as minoxidil, latanoprost, fluridil, spironolactone and their combinations are known.

[0014] Other products exist and belong to the cosmetic field. Among them, we can cite for example aminexil® and stemoxydine®.

[0015] Nevertheless, consumers are increasingly looking for effective natural alternatives that would delay the process of "hair loss" or "excessive hair loss."

[0016] Furthermore, the formulation of environmentally friendly cosmetic products, i.e. those whose design and development take environmental issues into account, is becoming a major concern to help meet global challenges.

[0017] It is therefore essential to offer more sustainable compositions that can respond to these environmental challenges. In this context, it is important to develop new cosmetic compositions with a better footprint. carbon, in particular by promoting the use of renewable raw materials and / or with a good index of naturalness and / or of natural origin and more particularly of plant origin while reducing the use of compounds of petrochemical origin.

[0018] Thus, there is a need to propose combinations of natural active ingredients which make it possible to effectively prevent and / or treat loss of hair density.

[0019] The applicant has surprisingly discovered that a composition comprising at least one compound of formula (I) and at least one gingerol in precise proportions makes it possible to modulate the level of expression of a series of genes associated with the HIF-1 biological pathway. This pathway is known in the literature for its involvement in hair loss (F Juchaux, T Sellathurai, V Perrault, F Boirre, P Delannoy, K Bakkar, J Albaud, A Gueniche, A Cheniti, S Dal Belo, L Souverain, M Le Balch, S Commo, S Thibaut, JF Michelet. “A combination of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol stabilizes hypoxia-inducible factor 1-alpha and improves hair density in female volunteers”, Int J Cosmet Sci. 2020 Apr;42(2): 167-173).Thus, the combination of at least one compound of formula (I), preferably niacinamide, or nicotinamide, or vitamin B3, with at least one gingerol, preferably in the form of extracts containing gingerols such as ginger extract, in precise proportions, has interesting properties as an active ingredient for inducing and / or stimulating the growth of keratin fibers such as hair, eyelashes, body hair, and eyebrows and / or slowing their loss, and in particular for treating alopecia, in particular androgenic alopecia.

[0020] The subject of the invention is therefore a cosmetic composition comprising in a physiologically acceptable medium:

[0021] - at least one compound of formula (I),

[0022] - at least one gingerol, and

[0023] - possibly at least one shogaol;

[0024] in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and

[0025] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1.

[0026] The present invention also relates to a cosmetic treatment method comprising at least one step of applying to the keratin materials a cosmetic composition according to the invention, to induce and / or stimulate the growth of keratin fibers and / or slow down their loss.

[0027] The present invention also relates to a cosmetic treatment method comprising at least one step of applying to keratin materials a cosmetic composition according to the invention, to treat alopecia, in particular androgenic alopecia.

[0028] The invention also relates to a non-therapeutic cosmetic use of a combination of active agents comprising:

[0029] - at least one compound of formula (I),

[0030] - at least one gingerol, and

[0031] - possibly at least one shogaol;

[0032] in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and

[0033] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1;

[0034] to induce and / or stimulate the growth of keratin fibers and / or slow their loss.

[0035] The invention also relates to a non-therapeutic cosmetic use of a combination of active agents comprising:

[0036] - at least one compound of formula (I),

[0037] - at least one gingerol, and

[0038] - possibly at least one shogaol;

[0039] in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and

[0040] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1;

[0041] for treating alopecia, in particular androgenic alopecia. Definition

[0042] For the purposes of the present invention, the term “cosmetic composition” means a composition comprising a physiologically acceptable medium, i.e. a medium compatible with the skin.

[0043] For the purposes of the present invention, the term "keratin materials" means materials comprising keratin such as skin, scalp and keratin fibers. In particular, the keratin materials are preferably human keratin materials.

[0044] For the purposes of the present invention, the term “keratin fibers” means keratin fibers, preferably human, such as hair, eyelashes, body hair and / or eyebrows, preferably eyelashes and hair, more preferably hair.

[0045] For the purposes of the present invention, the term “slowing down the loss of keratin fibers” means slowing down or reducing the loss of keratin fibers.

[0046] By "stimulating the growth of keratin fibers" is meant, within the meaning of the present invention, promoting or improving the growth of existing keratin fibers, in particular increasing the length and / or diameter of existing keratin fibers. and / or increase the number of keratin fibers and / or increase the density of keratin fibers.

[0047] By "inducing the growth of keratin fibers" is meant, within the meaning of the present invention, promoting or improving the growth of new keratin fibers, in particular the density of keratin fibers (by the growth of new keratin fibers).

[0048] By "treating alopecia, in particular androgenic alopecia" is meant, within the meaning of the present invention, promoting or improving the growth of new keratin fibers, or slowing down or reducing the loss of keratin fibers in people suffering from alopecia, in particular androgenic alopecia.

[0049] By "mass ratio [compound(s) of formula (I) / gingerol(s)]" is meant the mass ratio of all the compounds of formula (I) present in the composition or in the combination of active agents relative to all the gingerols present (or total gingerols) in the composition or in the combination of active agents. It is calculated by dividing the sum of the masses of all the compounds of formula (I) present by the sum of the masses of all the gingerols present.

[0050] By "mass ratio [gingerol(s) / shogaol(s)]" is meant the mass ratio of all the gingerols present in the composition or in the combination of active agents relative to all the shogaols present in the composition or in the combination of active agents. It is calculated by dividing the sum of the masses of all the gingerols present by the sum of the masses of all the shogaols present.

[0051] By “alkyl” is meant a monovalent linear or branched saturated hydrocarbon chain.

[0052] By C1-C4 alkyl is meant an alkyl radical comprising 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, and preferably methyl or ethyl.

[0053] By (hydroxy)alkyl C1-C4 is meant a C1-C4 alkyl radical substituted by a hydroxy radical.

[0054] By “heterocycle” is meant a cyclic radical of which at least one of the links designates a heteroatom preferably chosen from N, O, S, more preferably N.

[0055] By "salt" is meant an addition salt with an organic or mineral acid or base. The addition salts with an acid are in particular chosen from addition salts with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, citric acid, succinic acid, tartaric acid, lactic acid, tosylic acid, benzenesulfonic acid, phosphoric acid or acetic acid. The addition salts with a base are in particular chosen from addition salts with bases such as alkali metal hydroxides, alkaline earth metal hydroxides, ammonia, amines or alkanolamines.

[0056] Composition

[0057] The composition according to the invention contains at least one compound of formula (I).

[0058] For the purposes of the invention, the compounds of formula (I) have the following structure, as follows: that their addition salts:

[0059] [Chem.l] (I)

[0060] in which • X represents the OR group or the NRaRb group - Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical such as methyl, or Ra and Rb can form together with the nitrogen atom which carries them a heterocycle of 5 or 6 members, said heterocycle being optionally substituted by one or more C1-C4 (hydroxy)alkyl radicals or one or more hydroxy groups; - R denotes a hydrogen atom or a C1-C4 alkyl radical such as ethyl or a C1-C4 (hydroxy)alkyl radical.

[0061] Preferably Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical such as methyl, more preferably Ra and Rb denote a hydrogen atom.

[0062] Preferably R denotes a hydrogen atom.

[0063] According to a preferred embodiment, the compounds of formula (I) are chosen from the following compounds (II) and (III), their mixtures, as well as their salts.

[0064] [Chem.2]

[0065] [Chem.3] (III)

[0066] According to a preferred embodiment, the at least one compound of formula (I) comprises the compound (II) named niacinamide or (3-pyridinecarboxamide) also known as nicotinamide. According to a preferred embodiment, the at least one compound of formula (I) is the compound (II) named niacinamide or (3-pyridinecarboxamide) also known as nicotinamide.

[0067] For example, we can cite the product Niacinamide PC® marketed by the company DSM NUTRITIONAL PRODUCTS.

[0068] Preferably, the composition comprises from 1% to 5% by weight of compound(s) of formula (I) relative to the total weight of the composition, preferably from 1.5% to 4.5% by weight, preferentially from 2% to 4%, relative to the total weight of the composition.

[0069] The composition according to the invention comprises at least one gingerol. Gingerols are compounds of the arylalkanol family which correspond to the following general formula (IV):

[0070] [Chem.4] OH (IV)

[0071] They are present in plants of the Zingiberaceae family.

[0072] In accordance with the invention, gingerols which correspond to the general formula (IV) mentioned above in which n is equal to 2, 4, 6 or 8 and which are known under the respective names of [4]-gingerol, [6]-gingerol, [8]-gingerol and

[10] -gingerol are preferably used.

[0073] Preferably, said at least one gingerol is a mixture of gingerols.

[0074] Preferably, said at least one gingerol is a mixture of gingerols, said mixture comprising at least [6]-gingerol.

[0075] Preferably, said at least one gingerol is a mixture of gingerols, said mixture comprising at least [6]-gingerol in a concentration of at least 50% by weight relative to the total weight of the mixture of gingerols.

[0076] Preferably, the composition comprises a ginger extract comprising said at least one gingerol, wherein the gingerol(s) is(are) present in the ginger extract in a concentration ranging from 10% to 35% by weight relative to the total weight of the ginger extract, preferably 12 to 32% by weight, even better from 14 to 30% by weight relative to the total weight of the ginger extract.

[0077] Preferably, the composition comprises a ginger extract comprising said at least one gingerol, said at least one gingerol being a mixture of gingerols comprising at least the [6]-gingerol present in the ginger extract in a concentration of at least 8% by weight relative to the total weight of the ginger extract, preferably at least 10% by weight, more preferably at least 13% by weight, even better at least 15% by weight relative to the total weight of the ginger extract.

[0078] Preferably, said at least one gingerol is chosen from [6]-gingerol, [8]-gingerol,

[10] -gingerol and their mixture.

[0079] Preferably, said at least one gingerol is present in the composition according to the invention in a content ranging from 0.00001% to 1% by weight of total gingerols relative to the total weight of the composition, preferably from 0.0001% to 0.5%, even better 0.0002% to 0.1% by weight of total gingerols relative to the total weight of the composition.

[0080] Preferably, the composition comprises a ginger extract comprising said at least one gingerol in which: - the concentration of [6]-gingerol is between 5 and 20% by weight relative to the weight of the extract, and more preferably between 12.5 and 17.5% by weight relative to the weight of the extract; and / or - the concentration of [8]-gingerol is between 1 and 5% by weight relative to the weight of the extract, and more preferably between 2 and 4% by weight relative to the weight of the extract; and / or - the concentration of

[10] -gingerol is between 1 and 10% by weight relative to the weight of the extract and more preferably between 3 and 7% by weight relative to the weight of the extract.

[0081] Said at least one gingerol may be in the form of extracts, by any extraction process known per se, of plants belonging to the Zingiberaceae family and, more particularly, of those belonging to the genus Zingiber and in particular to the species Zingiber officinalis (commonly known as ginger). More particularly, said at least one gingerol may be in the form of rhizome extracts of these plants (also referred to herein as ginger root extract).

[0082] In particular, the ginger rhizome extract may be in the form of ground material, powder or liquid, it is preferably in the form of liquid.

[0083] The ginger rhizome extract may in particular be obtained by supercritical CO2 extraction from ginger rhizome fragments, for example ginger rhizome powder. The ginger rhizome extract used is preferably an extract obtained by supercritical CO2 extraction such as that marketed under the name GINGER CO2 by the company FLAVEX.

[0084] In the case where said at least one gingerol is in the form of ginger rhizome extract, said extract is then preferably present in a content ranging from 0.00003 to 1% by weight, preferably from 0.0001 to 0.5% by weight, more preferably 0.001 to 0.3% by weight, relative to the total weight of the composition.

[0085] Said at least one gingerol can also be obtained by chemical synthesis, for example according to the processes described by BANNO and MUKAIYAMA, Bull. Chem. Soc. Japan, 49(5), 1453-1454 (1976). Said at least one gingerol can also be obtained by purification or enrichment of natural plant extracts such as extracts of plants belonging to the Zingiberaceae family, in particular those belonging to the genus Zingiber, more particularly to the species Zingiber officinalis.

[0086] In particular, the applicant has discovered that a synergistic effect between: - said at least one compound of formula (I), preferably chosen from the compounds of formula (II) and (III) and their mixture, more preferably niacinamide, and - said at least one gingerol,

[0087] could be obtained when these are used in a particular ratio.

[0088] Thus, according to the invention, the mass ratio [compound(s) of formula (I) / gingerol(s)] in the composition is less than or equal to 150, preferably less than or equal to 140, more preferably less than 130, advantageously it is between 0.01 and 150, preferably between 0.1 and 140, and more preferably between 0.1 and 130.

[0089] According to one embodiment, the mass ratio [compound(s) of formula (II) and / or (III) / gingerol(s)], preferably the mass ratio [compound(s) of formula (II) / gingerol(s)], in the composition is less than or equal to 150, preferably less than or equal to 140, more preferably less than 130, advantageously it is between 0.01 and 150, preferably between 0.1 and 140, and more preferably between 0.1 and 130.

[0090] According to one embodiment, the mass ratio [compound(s) of formula (I) / [6]-gingerol] in the composition is less than or equal to 250, preferably less than or equal to 200, more preferably less than 195, advantageously it is between 0.01 and 250, preferably between 0.1 and 200, and more preferably between 0.1 and 195.

[0091] According to one embodiment, the mass ratio [compound(s) of formula (II) and / or (III), preferably of formula (II) / [6]-gingerol] in the composition is less than or equal to 250, preferably less than or equal to 200, more preferably less than 195, advantageously it is between 0.01 and 250, preferably between 0.1 and 200, and more preferably between 0.1 and 195.

[0092] In one embodiment of the invention the mass ratio [compound of formula (I) / ginger extract] in the composition is less than or equal to 40, less than or equal to 35, preferably less than or equal to 30, advantageously it is between 0.01 and 35, preferably between 0.03 and 30.

[0093] The composition according to the invention optionally comprises at least one shogaol. Shogaols are compounds of the arylalkanone family which correspond to the following general formula (V):

[0094] [Chem.5] (V)

[0095] They are present in plants of the Zingiberaceae family.

[0096] According to the invention, shogaols corresponding to the general formula (V) mentioned above are preferably used, in which n is equal to 1, 2, 4, 6 or 8 and which are respectively called [3]-shogaol, [4]-shogaol, [6]-shogaol, [8]-shogaol and

[10] -shogaol. Preferably, said at least one shogaol is chosen from [6]-shogaol, [8]-shogaol,

[10] -shogaol and their mixture.

[0097] Shogaols can be produced by drying or cooking ginger. Shogaols can be extracted from the rhizomes of Zingiberaceae by methods identical to those used for the extraction of gingerols.

[0098] Preferably, said at least one shogaol is present in the composition according to the invention in a content of less than 0.02% by weight of total shogaols relative to the total weight of the composition, preferably less than 0.01%, more preferably less than 0.005%, preferably less than 0.0002%, more particularly less than 0.0001% by weight of total shogaols relative to the total weight of the composition.

[0099] Preferably, the composition comprises a ginger extract comprising said at least one shogaol in which: - the concentration of [6]-shogaol is between 0.1 and 5% by weight relative to the weight of the extract, and more preferably between 1.5 and 2.5% by weight relative to the weight of the extract; and / or - the concentration of [8]-shogaol is between 0.1 and 3% by weight relative to the weight of the extract, and more preferably between 0.3 and 0.5% by weight relative to the weight of the extract; and / or - the concentration of

[10] -shogaol is between 0.01 and 1% by weight relative to the weight of the extract, and more preferably between 0.08 and 0.2% by weight relative to the weight of the extract.

[0100] Preferably, said at least one shogaol may be in the form of a ginger extract (Zingiber officinale), preferably a ginger rhizome extract. Said at least one shogaol may be in the form of extracts, by any extraction method known per se, of plants belonging to the Zingiberaceae family and, more particularly, of those belonging to the genus Zingiber and in particular to the species Zingiber officinalis (commonly called ginger). More particularly, said at least one shogaol may be in the form of rhizome extracts of these plants (also called herein ginger root extract).

[0101] In particular, the ginger rhizome extract may be in the form of ground material, powder or liquid, it is preferably in the form of liquid.

[0102] The ginger rhizome extract may in particular be obtained by supercritical CO2 extraction from ginger rhizome fragments, for example ginger rhizome powder. The ginger rhizome extract used is preferably an extract obtained by supercritical CO2 extraction such as that marketed under the name GINGER CO2 by the company FLAVEX.

[0103] In one embodiment of the invention, the composition comprises a ginger extract comprising said at least one gingerol and said at least one shogaol. Preferably, this ginger extract, preferably from ginger rhizome, is composed of: - 10% to 35% by weight of total gingerols relative to the total weight of the extract, preferably from 12% to 32%, and more preferably from 14-30% by weight of total gingerols relative to the total weight of the extract; - less than 15% by weight of total shogaols relative to the total weight of the extract, preferably less than 10%, and more preferably less than 5% by weight of total shogaols relative to the total weight of the extract.

[0104] Preferably, the composition comprises a ginger extract comprising said at least one gingerol and said at least one shogaol, wherein: - the concentration of [6]-gingerol is between 5 and 20% by weight relative to the weight of the extract, and more preferably between 12.5 and 17.5%; and / or - the concentration of [8]-gingerol is between 1 and 5% by weight relative to the weight of the extract, and more preferably between 2 and 4%; and / or - the concentration of

[10] -gingerol is between 1 and 10% by weight relative to the weight of the extract and more preferably between 3 and 7%; and / or - the concentration of [6]-shogaol is between 0.1 and 5% by weight relative to the weight of the extract, and more preferably between 1.5 and 2.5%; and / or - the concentration of [8]-shogaol is between 0.1 and 3% by weight relative to the weight of the extract and more preferably between 0.3 and 0.5%; and / or - the concentration of

[10] -shogaol is between 0.01 and 1% by weight relative to the weight of the extract and more preferably between 0.08 and 0.2%.

[0105] In the embodiment of the invention where the composition comprises a ginger extract comprising said at least one gingerol and said at least one shogaol, the extract may be a ginger rhizome extract present in the composition in a content ranging from 0.02 to 1% by weight, preferably from 0.03 to 0.5% by weight, more preferably from 0.05 to 0.3% by weight, relative to the total weight of the composition. The ginger root extract used is preferably an extract obtained by supercritical CO2 extraction such as that marketed under the name GINGER CO2 by the company FLAVEX.

[0106] The applicant has also discovered that when the composition according to the invention comprises at least one shogaol, the effect of said composition could be reduced if the mass ratio between the gingerols and the shogaols is strictly less than 1.

[0107] Thus according to the invention, when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1, preferably greater than 3, more preferably greater than 6, even more preferably greater than 9. In a preferred embodiment, this ratio is between 1 and 15, preferably between 5 and 12, more preferably between 8 and 10.

[0108] According to one embodiment of the invention, the mass ratio of [6], and [8], and

[10] -gingerol to [6], and [8], and

[10] -shogaol is greater than or equal to 3, preferably greater than 3, more preferably greater than 6, even more preferably greater than 9. In a preferred embodiment, this ratio is between 3 and 15, preferably between 5 and 12, more preferably between 8 and 10.

[0109] In one embodiment, the composition according to the invention does not comprise any active agents other than: - at least one compound of formula (I), preferably at least one compound of formula (II) and / or (III), more preferably a compound of formula (II), - at least one gingerol, and - at least one shogaol.

[0110] The composition preferably contains a physiologically acceptable medium.

[0111] This physiologically acceptable medium may comprise water and optionally one or more physiologically acceptable organic solvents chosen for example from lower alcohols containing from 1 to 8 carbon atoms and in particular 1 to 6 carbon atoms, such as ethanol, isopropanol, propanol, butanol; polyethylene glycols containing from 6 to 80 ethylene oxides; polyols such as propylene glycol, isoprene glycol, butylene glycol, glycerin, sorbitol, 1,3-propanediol.

[0112] It can also be an anhydrous medium, containing oils and / or fatty substances other than oils.

[0113] When the physiologically acceptable medium is an aqueous medium, it has a pH compatible with the skin, preferably ranging from 3 to 8 and better still from 4 to 7.

[0114] When the composition comprises an aqueous or hydroalcoholic medium, it is possible to add a fatty (or oily) phase to this medium.

[0115] The composition according to the invention is in particular a composition intended for topical application to the scalp and / or keratin fibers.

[0116] The composition according to the invention may also comprise one or more additional compounds chosen in particular from surfactants, preferably chosen from non-ionic, anionic, cationic and amphoteric surfactants, conditioning agents preferably chosen from cationic polymers, silicones, polymeric or non-polymeric, natural or synthetic thickening agents, UV filters, fillers such as nacres, titanium dioxide, resins and clays, perfumes, peptizers, vitamins other than vitamin B3, preservatives, acidic agents, alkaline agents, additional active agents other than the compounds according to the invention intended to further improve the activity on regrowth and / or on slowing down hair loss, and having already been described for this activity, such as nicotinic acid esters, including in particular tocopherol nicotinate,benzyl nicotinate and C1-C6 alkyl nicotinates such as methyl or hexyl nicotinates; hair regrowth promoting agents chosen from pyrimidine 3-oxide derivatives such as 2,4-diaminopyrimidine-3-N-oxide (Aminexil), pyridine-dicarboxylate derivatives or one of its salts such as those described in FR2838336 such as pyridine-2,4-dicarboxylate dimethyl ester; and a mixture of these compounds.

[0117] The above additional compounds may each be present in an amount varying from 0.01% to 20% by weight relative to the total weight of the composition.

[0118] The composition according to the invention is intended for cosmetic use by topical application to the scalp and / or keratin fibers, and more specifically to the scalp, hair and eyelashes, body hair, eyebrows.

[0119] Depending on the method of application, this composition can be presented in all the galenic forms normally used in the cosmetic field, such as lotion, serum, milk, cream, gel, ointment, pomade, powder, balm, patch, soaked pad, soap, bar, foam. It can be formulated in the form of an emulsion, such as a direct oil-in-water emulsion or a reverse water-in-oil emulsion.

[0120] For topical application to the scalp and / or keratin fibers, the composition may have the form in particular of an aqueous or hydro-alcoholic solution or suspension, of an emulsion or dispersion of liquid or semi-liquid consistency obtained by dispersing a fatty phase in an aqueous phase (O / W) or vice versa (W / O), of a dispersion or emulsion of soft consistency, of an aqueous or hydro-alcoholic gel, or of microcapsules or microparticles, or of vesicular dispersions of ionic and / or non-ionic type.

[0121] The composition may also be in the form of a foam or in the form of an aerosol composition also comprising a pressurized propellant.

[0122] Preferably, for topical application to the scalp and / or keratin fibers, in particular the scalp or hair, the composition may be in the form of a hair lotion, a shampoo, a conditioner, a hair styling product (hairspray, styling product, styling gel), a hair mask, a cream or a foaming hair cleansing gel.

[0123] According to a preferred embodiment, the composition is in the form of a cream or lotion, shampoo or conditioner.

[0124] Method

[0125] The present invention also relates to a non-therapeutic cosmetic treatment process comprising the application to keratin materials of the composition described above, to induce and / or stimulate the growth of keratin fibers and / or slow their loss.

[0126] The present invention also relates to a non-therapeutic cosmetic treatment method comprising the application to keratin materials of the composition described above, for treating alopecia, in particular androgenic alopecia.

[0127] In particular, the method comprises applying the composition to the scalp and / or fibers, then, optionally, rinsing, after a leave-on time of the composition which may vary from 1 minute to 30 minutes.

[0128] Preferably, the cosmetic composition is not rinsed.

[0129] Use

[0130] The subject of the present invention is the non-therapeutic cosmetic use of a combination of active agents comprising:

[0131] - at least one compound of formula (I) as described above,

[0132] - at least one gingerol, and

[0133] - possibly at least one shogaol;

[0134] in which the mass ratio [compound of formula (I) / gingerol(s)] is less than or equal to 150, and

[0135] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1;

[0136] to induce and / or stimulate the growth of keratin fibers and / or slow their loss.

[0137] The present invention also relates to the non-therapeutic cosmetic use of a combination of active agents comprising:

[0138] - at least one compound of formula (I) as described above,

[0139] - at least one gingerol, and

[0140] - possibly at least one shogaol;

[0141] in which the mass ratio [compound of formula (I) / gingerol is less than or equal to 150, and

[0142] when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1;

[0143] for treating alopecia, in particular androgenic alopecia.

[0144] Preferably, the combination of active agents used according to the invention comprises the same active agents in the same concentrations and / or proportions as described above for the composition according to the invention.

[0145] The invention will appear more clearly on reading the description which follows, given solely by way of non-limiting example, and made with reference to the drawings in which:

[0146] Furthermore, the expression “at least one” used in the present description is equivalent to the expression “one or more”. Figure#:

[0147] [Fig. 1] [Fig. 1] presents a histogram representing the level of activation of the HIF-1 pathway as a function of the different niacinamide / ginger root extract mass ratios tested. Example:

[0148] Evaluation of HIF-L pathway activation for anti-fall application

[0149] The aim of this study is to compare the effectiveness of the Niacinamide-extra association Ginger roots to the effectiveness of the two compounds when separated on the activation of the HIF-1 pathway. This activation is measured by monitoring the level of expression of genes under the control of the HIF-1 alpha (Hypoxia Induced Factor 1 alpha) factor by quantitative RT-PCR.

[0150] The genes studied are: EGLN3, BNIP3, CA9, VEGFA.

[0151] The tests were carried out on cultured human keratinocytes, seeded on 48-well plates, coated with bovine collagen I. The plates were prepared according to the following procedure: the 0.1 mg / ml bovine collagen I solution was prepared by dilution in a phosphate-buffered saline (PBS) solution of bovine collagen I. Each well was immersed with 1 ml of this dilution, which was left at the bottom of the wells for 1 hour at 37°C. At the end of the incubation, the collagen solution was removed and the wells were rinsed twice with 1 ml of PBS. The plates were then stored at 4°C until use.The tests are carried out on primary human keratinocytes at a rate of 23,800 cells / cm2 of wells coated with bovine collagen I as explained previously, followed by culture for 72 hours in the presence of 500 pL of KGM medium, with supplement: 0.1% by weight of commercial gentamicin / amphotericin sulfate mixture, 0.4% by weight of bovine pituitary extract, 0.1% by weight of insulin, 0.1% by weight of hydrocortisone and 0.1% by weight of epidermal growth factor (or recombinant human EGF), at 37°C under a water-saturated atmosphere containing 5% CO2.

[0152] The cells were then treated with the compounds niacinamide and ginger root extract (containing 15.5% [6]-Gingerol, 3.6% [8]-Gingerol and 5.5%

[10] -Gingerol; 2.1% [6]-shogaol, 0.46% [8]-shogaol and 0.17%

[10] -shogaol) at the highest non-cytotoxic concentrations (0.2 mg / mL and 0.01 mg / mL respectively), for 48 hours under normoxia (21% oxygen). Following this culture and treatment, the cell lawns were washed with phosphate-buffered saline (or PBS) and then lysed using a lysis buffer. RNA was then extracted using the RNeasy Isolation Kit and the Qiacubestation. RNA quantity and quality were checked using the Perkin-Elmer LabChip® GX Bioanalyzer before performing reverse transcription (RT) using the Qiagen kit and as recommended.The cDNA obtained following RT was then amplified by quantitative real-time PCR calculations using a specific kit and a thermocycler. The PCRs were performed in triplicate (n=3).

[0153] Priming was performed using specific standard primers, and the SYBR Green brand fluorescent probe. PCR was performed in three phases: - denaturation phase for 10 minutes at 95°C, - amplification phase which consists of 45 cycles including a 30-second denaturation step at 95°C, a 30-second hybridization step at 60°C, and an elongation step at 72°C for 30 seconds, - fusion phase to ensure the quality of hybridizations. The incorporation of SYBR Green into the amplified DNA was measured continuously during the amplification cycles.

[0154] These measurements make it possible to obtain fluorescence intensity curves as a function of PCR cycles and thus evaluate the relative expression of each marker from the cycle thresholds (Ct), corresponding to the number of cycles necessary to correctly detect a fluorescence level. For each marker and for each condition, the relative expression (RE) value was normalized with respect to the expression of the reference gene RPL 13. The expression of each gene is normalized by that of the “stable reference gene” (or “housekeeping gene” RPL 13A, ribosomalgen).

[0155] The results are expressed via the "fold change" (Fc) of gene expression compared to the control condition (without treatment).

[0156] [Table 1] Table 1 Name Abbreviation Registration number Carbonic anhydrase IX CA9 NM_001216 BCL2 / adenovirus El B 19 kDa- interacting protein BN1P3 NM_004052 Prolyl hydroxylase EGLN3 (or PHD3) NM_022073 Vascular Endothelial Growth Factor VEGFA NP_001165097 Ribosomal protein L 13 RPL13 NM_000977

[0157] RESULTS AND CONCLUSIONS 1. Synergy of the two active ingredients Niacinamide - Ginger extract including gingerols#

[0158] All results are expressed through the modulation factor (fold change) compared to the untreated control after normalization of the relative expressions compared to the expression of a housekeeping gene (RPL13). The expression of a gene is considered to be stimulated when it is multiplied by at least 1.5.

[0159] Table 2 shows the effects of the compounds niacinamide and Ginger Extract, alone and in combination, on the expression of a selection of genes related to the described effects of hypoxia for an anti-hair loss benefit.

[0160] [Table 2] Table 2 EGLN3 BNIP3 CA9 VEGF Niacinamide 0.3mg / mL in DMSO 2.13 1.34 1.96 0.89 Ginger root extract 0.0 Img / mL in DMSO 1.58 0.93 1.51 1.78 ASSOCIATION of the 2 compounds Niacinamide 0.3mg / mL + Ginger root extract 0.01mg / m L in DMSO 4.09 4.16 6.86 2.34

[0161] The results show a synergistic effect of the Niacinamide and ginger root extract association. Indeed, treated with this association, all the genes are expressed with a modulation factor well above 1.5 compared to the control, which confirms the significant effect of this association, which is not the case for the raw materials tested separately. The Niacinamide-Ginger root extract association induces a significant stimulation of the expression of the EGLN3, BNIP3, CA9 and VEGF genes which are described in the literature as being associated with the HIF-1 biological pathway (Pouyssegur J et al., MEDECINE / SCIENCES 2002; 18: 70-8). When the HIF-1 transcription factor is stabilized (in a hypoxic environment or following treatment allowing its activation), it is translocated into the nucleus of cells and activates a large number of genes, including EGLN3, BNIP3 and CA9 and VEGF, associated with the regeneration of tissues such as skin and hair.

[0162] The stimulation of the expression of these genes in the presence of the Niacinamide-Ginger root extract association is greater than the addition of the effects of two compounds applied separately. 1. Mass ratios of niacinamide and gingerol concentrations to activate HIF-1#

[0163] Table 3 below and [Fig.l] show the different ratios of concentrations of Niacinamide and Ginger Root Extract tested and their effects on the activation of the HIF-1 pathway.

[0164] [Table 3] Table 3 NIACINAMIDE (g / 100g) % Ginger root extract (g / 100g) % Total gingerols (g / 100g) M ass RATIO Niacinamide / Ginger root extract M ass RATIO Niacinamide / total gingerols Average of the modulation factor of the expression of the genes EGLN3, BNIP3, CA9 and VEGFA. standard deviation 0.000033 0.001 0.000246 0.033 0.134 2.38 na 0.0001 0.00025 0.000061 5 0.4 1.63 2.78 na 0.001 0.001 0.000246 1 4.07 1.58 na 0.0025 0.001 0.000246 2.5 10.16 2.69 0.39 0.0025 0.001 0.000246 2.5 10.16 0.0025 0.001 0.000246 2.5 10.16 0.0025 0.001 0.000246 2.5 10.16 0.00025 0.0001 0.000024 6 2.5 10.16 0.0025 0.0005 0.000123 5 20.33 5.00 0.45 0.005 0.001 0.000246 5 20.33 0.005 0.001 0.000246 5 20.33 0.005 0.001 0.000246 5 20.33 0.005 0.001 0.000246 5 20.33 0.005 0.001 0.000246 5 20.33 0.005 0.0005 0.000123 10 40.65 2.91 na 0.02 0.001 0.000246 20 81.30 20.00 0.84 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.02 0.001 0.000246 20 81.30 0.015 0.0005 0.000123 30 121.95 2.45 0.01 0.001 0.000033 0.000008 12 30 121.95 0.02 0.0005 0.000123 40 162.60 1.27 na 0.0005 0.00001 0.000002 46 50 203.25 1.10 0.40 0.02 0.0004 0.000098 4 50 203.25

[0165] The results show that Niacinamide and ginger root extract concentration ratios less than or equal to 30 / 1 are effective in stimulating gene expression related to the described effects of hypoxia for an anti-hair loss benefit: Fold Change > 1.5.

[0166] When the concentration ratio is greater than 30 / 1, the association is no longer effective. 1. Demonstration of the active ingredients responsible for the effectiveness of Ginger root extract: Gingerols

[0167] As detailed in the component analysis below, the ginger root extracts used in the examples according to the invention contain on average 24.6% gingerols, and in particular 15.5% [6]-gingerol 3.6% [8]-gingerol and 5.5%

[10] -gingerol.

[0168] Table 4 represents the comparison of the activation of the HIF-1 pathway by the implementation of the protocol as detailed in point 1, between the Niacinamide-Ginger root extract associations (at a ratio of 30 / 1 and containing 24.6% gingerols) and Niacinamide-Gingerols (at a concentration of gingerols corresponding to the 24.6% contained in the ginger extract).

[0169] [Table 4] Table 4 TESTED ASSOCIATIONS (mg / ml) TESTED ASSOCIATIONS (g per 100g) NHIF-1 ACTIVATION (Fold Chang e) Standard Deviation Niacinamide 0.3mg / mL Niacinamide 0.03% 3.1 0.488 + Ginger root extract 0.01mg / mL in DMSO + Ginger extract 0.001% or 0.000246% of total gingerols in DMSO (niacinamide / gingerol ratio = 121.95) Niacinamide 0.3mg / mL + [6]-Gingerol (0.00155mg / mL) + [8]-Gingerol (0.00036mg / mL) +

[10] -Gingerol (0.00055mg / mL) in DMSO Niacinamide 0.03% + [6]-Gingerol (0.000155%) + [8]-Gingerol (0.000036%) +

[10] -Gingerol (0.000055%) or 0.000246% of total gingerols in DMSO (niacinamide / gingerol ratio = 121.95) 3.0 0.2

[0170] The efficacy is identical with both associations. These results show that the activity of ginger root extract to activate the HIF-1 pathway is carried by gingerols. 1. Gingerol / shogaol mass ratio for activating HIF-1

[0171] Ginger root extract may also contain Shogaols: [6]-Shogaol, [8]-Shogaol and

[10] -Shogaol.

[0172] Table 5 represents the comparison of the activation of the HIF-1 pathway by the implementation of the protocol as detailed in point 1 above, between the Niacinamide-gingerols and Niacinamide-gingerols-shogaols associations at different ratios of [gingerol(s) / shogaol(s)]. When the ratio [gingerol(s) / shogaol(s)] is strictly less than 1 (0.90), the activity carried by the niacinamide-gingerol(s) association is degraded. Thus, it is observed that, in the presence of shogaol(s), it is necessary that the ratio [gingerol(s) / shogaol(s)] be greater than or equal to 1 to maintain the activation efficiency of the HIF-1 pathway.

[0173] [Table 5] Table 5 ASSOCIATIONS TESTED (mg / ml) ASSOCIATIONS TESTED (g per 100g) Fold Change Standard Deviation Niacinamide 0.3mg / mL + Niacinamide 0.03% + 4.09 1.1 [6]-Gingerol (0.00155mg / mL) + [8]-Gingerol (0.00036mg / mL) +

[10] -Gingerol (0.00055mg / mL) in DMSO [6]-Gingerol (0.000155%) + [8]-Gingerol (0.000036%) +

[10] -Gingerol (0.000055%) in DMSO or 0.000246% of total ginger (mass ratio niacinamide / gingerols = 121.95) Niacinamide 0.3mg / mL + [6]-Gingerol (0.00155mg / mL) + [8]-Gingerol (0.00036mg / mL) +

[10] -Gingerol (0.00055mg / mL) + [6]-Shogaol (0.0002 Img / mL) + [8]-Shogaol (0.000046mg / mL) +

[10] -Shogaol (0.000017mg / mL) in DMSO Niacinamide 0.03% + [6]-Gingerol (0.000155%) + [8]-Gingerol (0.000036%) +

[10] -Gingerol (0.000055%) or 0.000246% of total ginger ois + [6]-Shogaol (0.000021%) + [8]-Shogaol (0.0000046%) +

[10] -Shogaol (0.0000017%) or 0.0000273% of total shoga ois in DMSO (mass ratio niacinamide / g ingerols = 121.95 and mass ratio gingerols / shoga ois = 9.01) 3.8 0.8 Niacinamide 0.3mg / mL + [6]-Gingerol (0.00155mg / mL) Niacinamide 0.03% + [6]-Gingerol (0.000155%) 0.22 0.04 + + [8]-Gingerol (0.00036mg / mL) [8]-Gingerol (0.000036%) + +

[10] -Gingerol (0.00055mg / mL)

[10] -Gingerol (0.000055% + ) [6]-Shogaol (0.0021mg / mL) or 0.000246% of total ginger + [8]-Shogaol (0.00046mg / mL) + + [6]-Shogaol (0.00021%)

[10] -Shogaol (0.00017mg / mL) e + nDMSO [8]-Shogaol (0.000046%) +

[10] -Shogaol (0.000017% ) or 0.000273% of total shogao 1s in DMSO (mass ratio niacinami / gingerols = 121.95 and mass ratio gingerols / s hogaols = 0.90)

Claims

Claims

1. Cosmetic composition comprising in a physiologically acceptable medium: - at least one compound of formula (I), [Chem.l] (I) in which - X represents the OR group or the NRaRb group - Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical such as methyl, or Ra and Rb can form together with the nitrogen atom which carries them a heterocycle of 5 or 6 members, said heterocycle being optionally substituted by one or more C1-C4 (hydroxy)alkyl radicals or one or more hydroxy groups; - R denotes a hydrogen atom or a C1-C4 alkyl radical such as ethyl or a C1-C4 (hydroxy)alkyl radical, - at least one gingerol, and - possibly at least one shogaol; in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1.

2. Composition according to claim 1, wherein said at least one gingerol is selected from: [6]-gingerol, [8]-gingerol and [10]-gingerol.

3.

4.

5.

6.

7.

8. Composition according to claim 1 or 2, wherein said at least one gingerol and / or said at least one shogaol is in the form of a ginger extract. Composition according to claim 3, in which the mass ratio [compound(s) of formula (I) / ginger extract] in the composition is less than or equal to 40. Composition according to any one of claims 1 to 4, wherein said at least one compound of formula (I) comprises niacinamide. Non-therapeutic cosmetic treatment process comprising at least one step of applying to keratin materials a cosmetic composition according to any one of claims 1 to 5, to induce and / or stimulate the growth of keratin fibers and / or slow their loss in a subject presenting a normal physiological state. Non-therapeutic cosmetic treatment method according to claim 6, in which the keratin fibers are chosen from hair, eyelashes, body hair, and / or eyebrows. Non-therapeutic cosmetic use of a combination of active agents comprising: - at least one compound of formula (I), [Chem.l] (I) in which - X represents the OR group or the NRaRb group - Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical such as methyl, or Ra and Rb can form together with the nitrogen atom which carries them a heterocycle of 5 or 6 members, said heterocycle being optionally substituted by one or more C1-C4 (hydroxy)alkyl radicals or one or more hydroxy groups; - R denotes a hydrogen atom or a C1-C4 alkyl radical such as ethyl or a C1-C4 (hydroxy)alkyl radical, - at least one gingerol, and - possibly at least one shogaol; in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1; to induce and / or stimulate the growth of keratin fibers and / or slow their loss in a subject presenting a normal physiological state.

9. Association of active agents comprising: - at least one compound of formula (I), [Chem.l] (I) in which - X represents the OR group or the NRaRb group - Ra and Rb independently denote a hydrogen atom or a C1-C4 alkyl radical such as methyl, or Ra and Rb can form together with the nitrogen atom which carries them a heterocycle of 5 or 6 members, said heterocycle being optionally substituted by one or more C1-C4 (hydroxy)alkyl radicals or one or more hydroxy groups; - R denotes a hydrogen atom or a C1-C4 alkyl radical such as ethyl or a C1-C4 (hydroxy)alkyl radical,

10.

11.

12.

13.

14. - at least one gingerol, and - possibly at least one shogaol; in which the mass ratio [compound(s) of formula (I) / gingerol(s)] is less than or equal to 150, and when said composition comprises at least one shogaol, then the mass ratio [gingerol(s) / shogaol(s)] is greater than or equal to 1; for its use in the treatment of alopecia, in particular androgenic alopecia. Use according to claim 8, wherein the keratin fibers are hair, eyelashes, body hair, and / or eyebrows. Non-therapeutic cosmetic use according to any one of claims 8 and 10, wherein said at least one gingerol is chosen from: [6]-gingerol, [8] gingerol and [10] gingerol. Combination of active agents according to claim 9, wherein the treatment of alopecia comprises promoting or improving the growth of new keratin fibers, or slowing down or reducing the loss of keratin fibers. Combination of active agents according to claim 12, in which the keratin fibers are hair, eyelashes, body hair, and / or eyebrows. Combination of active agents according to any one of claims 9 and 12 to 13, in which said at least one gingerol is chosen from: [6]-gingerol, [8] gingerol and [10] gingerol.