WO2022268643A1

WO2022268643A1 - Use of zerumbone for a cosmetic treatment

Info

Publication number: WO2022268643A1
Application number: PCT/EP2022/066480
Authority: WO
Inventors: Caroline RINGENBACH; Thibault MARCHAND; Philippe Mondon
Original assignee: Sederma
Priority date: 2021-06-22
Filing date: 2022-06-16
Publication date: 2022-12-29
Also published as: FR3124082B1; FR3124082A1

Abstract

According to the invention, zerumbone, derivative and/or analog thereof, or of a plant extract containing it, is used for a treatment of hyperpigmented areas on the skin (to prevent them from appearing and/or to treat them once they are present so that they fade and/or disappear), through the phosphorylation of Akt, ERK-1 and ERK-2 metabolic pathways, and the reduction of PGE2 production, influencing the tyrosinase and melanin production, therefore its transfer from the melanosome to the keratinocytes. The zerumbone or the plant extract containing it is from the Zingiberaceae family and the extraction is carried out using a supercritical fluid.

Description

USE OF ZERUMBONE FOR A COSMETIC TREATMENT

TECHNICAL FIELD

The present invention relates to a new non-therapeutic cosmetic use of the zerumbone molecule, derivative and/or analog thereof, or of a plant extract containing it.

It also relates to novel compositions for this use.

The fields of application of the present invention are the ingredients and compositions for the cosmetic industry, cosmeceutical, dermopharmacy products and personal care and hygiene, zerumbone, derivative and/or analog thereof, or of a plant extract containing it, being used for the treatment of the skin of mammals, human or animals, and its appendages.

BACKGROUND ART

Various phenomena influence the quality of the skin and various parameters make it appear less homogeneous, for example wrinkles, fine lines, dryness, loss of elasticity and pigmentation heterogeneity. Aesthetic treatments make it possible to remove or mask some of these skin imperfections, making it possible to beautify the skin by making it more homogeneous.

One of the causes of skin pigmentation is sun exposure, inducing the associated mechanism called "melanogenesis”. This pigmentation can be homogeneous or inhomogeneous.

Other causes of inhomogeneous pigmentation exist, such as a reaction following a treatment, pregnancy mask, or hyperpigmentation due to an inflammatory reaction of the skin, for example an acne spot, leaving an unsightly pigmented spot which remains more or less long or the periorbital dark circles which contribute to make the person appear older, more tired.

In addition, an acceleration of melanogenesis occurs as the skin ages, resulting in brown spots that are often considered unsightly.

SUMMARY OF THE INVENTION

The aim of the present invention is to provide a non-therapeutic cosmetic treatment and a and an associated product for homogenize the complexion, more precisely, by preventing and/or treating skin hyperpigmentation.

By « hyperpigmentation », means according to the present invention, a pigments spot resulting of a non- homogeneous aspect of the skin color. It is the consequence of the excessive quantities’ melanin production at the level of certain skin areas.

To this end, the subject matter of the present invention is the use of zerumbone, derivative and/or analog thereof, or of a plant extract containing it, for a cosmetic non-therapeutic treatment, adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fade and/or make hyperpigmented areas on the skin disappear.

Preferably, the non-therapeutic cosmetic treatment is a topical treatment.

« Topical treatment » or « topical use » means according to the invention, an application that is intended to act where it is applied: skin, mucosa and/or appendages. Zerumbone is a sesquiterpene (3 isoprene units) with a "humulane" type skeleton. His name is the 2E, 6E, 9E- Humulatrien-8-one. Its developed formula is:

Zerumbone was isolated from roots of Zingiber zerumbet (L.) Smith (synonyms: Amomum zerumbet L, Zingiber amaricans Blume, Zingiber aromaticum Val. Zingiber Morale Val., Zingiber zerumbet (L.) Roscoe), also known as « Shampoo Ginger », « Pinecone Ginger » or « Awapuhi » in Taiwan or « Wild ginger » in China), a plant found in Southeast Asia. Other plants are said to contain zerumbone as Alpinia galanga or Syringa pinnafolia. Zerumbone has anti-inflammatory and anti-radical properties. Effects on cancer in general, especially leukemia, and also effects on the HIV virus are described.

US7588788 describes a nutraceutical composition containing an extract of the roots of Zingiber zerumbet (L.) Smith to regulate the immune system and more particularly to prevent and treat allergic disorders.

FR2985426 describes a topic use of zerumbone for a slimming treatment.

FR2985424 describes a topic use of zerumbone for the treatment of the deficiencies of the capillary network of the skin, resulting in feelings of heaviness and tingling in the lower limbs. It also helps to treat micro- subcutaneous oedemas, including bags and/or dark circles under the eyes.

The treatment according to the invention makes it possible to act on three causes intended to prevent the appearance of hyperpigmented areas on the skin and/or to fade them and/or make them disappear: phosphorylation of Akt metabolic pathways (or protein kinase B, essential protein in mammalian cell signaling), ERK-1 and ERK-2 (or « Extracellular signal-regulated kinases », add phosphate groups to other proteins to activate them) reducing the transcriptional activity of MITF (or « Microphthalmia- Associated Transcription Factor », transcription factor involved in melanocyte development and the survival of these cells) in charge to synthesize melanocytes enzymes; reduce PGE2 production (or prostaglandin E2), responsible for the formation and extension of dendrites of the melanocytes; and reduce tyrosinase production (enzyme with an intermediate role to form melanin) and melanin.

The appearance of pigmented spots on the skin is due to the production of melanin. For this purpose, the cellular protein MITF of the melanocyte synthesizes enzymes such as tyrosinase and TRP1 and 2 (or « Tyrosinase Related Proteins »).

The cellular protein MITF controlled by the CREB protein (or « C-AMP Response Element-Binding Protein », essential protein for the regulation of gene expression), which, when phosphorylated, combines with the CRE protein (or «C-AMP Response Element », enzyme for carrying out specific recombination) and triggers the formation of MITF. To be active, cellular protein MITF must then adopt a particular shape to match the region of the genes encoding the proteins to be produced. This conformational change is driven by GSK3-b (« Glycogen synthase kinase 3 beta » or a phosphorylating protein or cellular protein MITF).

Thus, if Akt is phosphorylated, it inactivates GSK3-b, and, by rebound effect, cellular protein MITF remains inactive. Moreover, if the ERK-1 and ERK-2 proteins are phosphorylated, they transfer their phosphorus to other areas of MITF, which falls prey to the cell's degradation system, the proteasome These phosphorylations help to reduce tyrosinase quantity, and therefore of melanin.

The epidermis, almost entirely composed of keratinocytes is a strong producer of PGE2. Fibroblasts, adipocytes and even melanocytes all produce PGE2. The PGE2 produced, even in tiny amounts, regulates certain functions of the melanocyte. In particular, it stimulates the formation and extension of dendrites but also the tyrosinase activity of the melanocyte via the CREB pathway. Thus, moderating the production of PGE2 in the keratinocyte will down-modulate overproduction of melanin, which represents another regulatory pathway of interest. Preferably, according to the invention, there is used as zerumbone source a plant extract of the family Zingiberaceae. Preferably, according to the invention, there is used a plant extract of the genus Zingiber, in particular an extract of Zingiber zerumbet (L.) Smith., d 'Alpinia galanga or de Syringa pinnafolia.

A plant extract according to the invention can be obtained either directly from the plant or by plant cell culture. Biological material (plant or plant cell culture) is extracted by any method of extraction, for example a conventional aqueous and/or organic solvent (e.g., alcoholic) extraction or by subcritical or supercritical fluid, microwave or ultra-sounds.

Preferably according to the invention, subcritical or supercritical fluid extraction is used. For example, liquid C02 is an excellent solvent for lipidic products. Inert, it hardly reacts with the molecules extracted and leaves no residue since it is evaporated at the end and captured to be reused. It provides an optimal yield and concentration of zerumbone.

The extraction can be performed on the whole plant or specific parts of the plant. Preferably according to the invention, the extract is obtained from the roots or rhizomes of the plant.

The present invention also encompasses derivatives of zerumbone including:

Simple substitutions on the skeleton: o OH and OAc in position 1; 5; 8; 14; 15 o COOH in position 14; 15 o O in position 5; 8 o CHO in position 14

Oxidation of the double bonds in epoxide, as for zerumbone oxide or some humulatrien-15,1 -elides (Asteriscunolide A to D) having a lactone ring between positions 1 (OH) and 15 (COOH).

The present invention also encompasses compounds close or analogs to zerumbone including:

The monoenes and dienes (e.g., Buddledone A (or 2E, 9E-Humuladien-8-one));

Compounds having a derivative cyclic structure close to the structure of b-Caryophyllene where carbons 2 and 10 are connected with migration of the double bonds in 9-10 in 10-2 and 2-3 to 3-15: Zerumbone, pure or the extract containing it, can be used pure or diluted in a physiologically acceptable medium or matrix. The nature of the medium or matrix is defined according to the properties of zerumbone or the extract, nature of the extraction solvent used for the extract production and also depending on the purpose of the composition formed: single ingredient, galenic form more sophisticated of a consumer final composition.

The present invention thus also proposes the use of zerumbone, derivative and/or analog thereof, or of a plant extract containing it, for the preparation of a cosmetic composition adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fade them and/or to make the hyperpigmented areas on the skin disappear.

To simplify the following description, we will use the term "zerumbone" unique to encompass "zerumbone, derivative and/or analog thereof ".

DETAILED DESCRIPTION

The present invention will be better understood in the light of the following description of an embodiment and in vitro tests.

1) Composition preparation for implementing the present invention

The present invention also relates to a cosmetic composition containing zerumbone and a physiologically acceptable medium, adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fad and/or remove hyperpigmented areas on the skin.

The expression "physiologically acceptable medium" means according to the present invention, without limitation, an aqueous or hydroalcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a micro-emulsion, an aqueous gel, an anhydrous gel, a serum, a dispersion of vesicles or a powder.

"Physiologically acceptable" means that the compositions are suitable for topical use, in contact with mucous membranes, nails, scalp, hairs and skin of mammals, particularly human, without risk of toxicity, incompatibility, instability, allergic response, and others.

This "physiologically acceptable medium" forms what is commonly called the excipient of the composition. Zerumbone according to the invention or a composition containing it may be applied locally on areas.

A composition according to the invention can be applied to the face, body, decollete, scalp, hair, eyelashes, body hair, in any form or vehicle known to those skilled in the art, in particular in the form of a solution, dispersion, emulsion, paste or powder, individually or as a premix or vehicled individually or as a premix in a bound form, incorporated or adsorbed in vectors such as macro-, micro-, or nanocapsules, macro-, micro- or , nanospheres, liposomes, oleosomes or chylomicrons, macro-, micro-, or nanoparticles or macro-, micro or nanosponges, micro- or nanoemulsions, or adsorbed on organic polymer powders, talcs, bentonites, spores or exines, and other inorganic or organic supports.

In cosmetics, applications can be proposed in particular in the ranges of skin care for the face, body, hair and body hair and ranges of make-up treatments.

The effective amount of zerumbone according to the invention, that is to say its dosage, depends on the destination of the composition. It depends on various factors, such as the age, the condition of the patient, the severity of the disorder or disease and the administration mode. An effective amount means a non-toxic amount enough to achieve the desired effect.

All percentages and ratios used herein are by weight of the total composition and all measurements are made at 25°C unless it is otherwise specified.

For indication, for a cosmetic face treatment, the European standard dosage of a cream is 2.72 mg/cm²/day/person and for a cosmetic body treatment the European standard dosage of a lotion is 0.5 mg/cm²/day/person.

According to other features, the cosmetic treatment method according to the invention can be combined with one or more other treatment methods targeting the skin such as luminotherapy, heat or aromatherapy treatments.

It is possible to offer devices with several compartments or kits may be proposed to apply the method described above which may include for example and non-restrictively, a first compartment containing a composition comprising zerumbone, and in a second compartment a composition containing another active ingredient and/or excipient, the compositions contained in the said first and second compartments in this case being considered to be a combination composition for simultaneous, separate or stepwise use in time, particularly in one of the treatment methods recited above.

In a cosmetic composition according to the invention, zerumbone, to be present in an effective amount, is generally present in an amount ranging from 0.000001% (0.01 ppm) and 15% (150000 ppm) based on the total weight of the composition, preferably ranging from 0.00001% (0.1 ppm) and 10% (100 OOOppm), depending on the destination of the composition and the more or less pronounced desired effect.

The excipient choice of the composition is made according to the constraints of the zerumbone or the extract containing it (stability, solubility, etc.), and if necessary, according to the intended galenic form envisaged afterwards

Zerumbone is soluble in particular in oil and in an alcohol. It can be incorporated in a composition by means of physiologically acceptable conventional solubilizers, for example and without limiting to this list: ethanol, propanol, isopropanol, propylene glycol, glycerin, butylene glycol, orpolyethylene glycol or any combination thereof. It may also be interesting to solubilize the extract using emulsifiers.

All galenic forms that can contain zerumbone and additional ingredients if present can be used, i.e. solution, emulsion, dispersion, suspension, unguent, cream, lotion, milk, ointment, gel, paste, powder, anhydrous preparation (for example oil for stick, "roll-on"), foam, essence, serum, spray, sprayable formulation, brushable, patch, adhesive material, individually or as a premix or vehicled individually or as a premix in a bound form, incorporated or adsorbed in vectors such as macro-, micro-, or nanocapsules, macro-, micro- or , nanospheres, liposomes, oleosomes or chylomicrons, macro-, micro-, or nanoparticles or macro-, micro or nanosponges, micro- or nanoemulsions, or adsorbed on organic polymer powders, talcs, bentonites, spores or exines, and other inorganic or organic supports.

The composition may be incorporated onto a non-woven or woven material, with natural or synthetic fibers, wool, or any material intended to come into contact with skin and that can be used in clothing, including tights and socks, shorty, day or night underwear, tissues, handkerchiefs or fabric to exert its cosmetic effect via the contact skin/textile and enable continuous topical delivery (cosmetic-textiles).

According to the invention, it is thus also proposed a woven or non-woven fabric comprising zerumbone for use in a topical non therapeutical cosmetic treatment of hyperpigmented areas of the skin.

The galenical formulations can enter in different product ranges for personal care and/or beauty products including skin care, cleaning, makeup, cleansing, sunscreen, artificial tanning, pre-shave, shaving or aftershave, moisturizer, humectant, emollient, conditioning, exfoliating, astringent, depilatories or antiperspirant, deodorant, deodorant, etc.

The Personal Care Products Council ("International cosmetic ingredient dictionary & handbook" (13th Ed. 2010) published by the "Cosmetic, Toiletry, and Fragrance Association, Inc.”, Washington, D.C.) describes a non limited wide variety of cosmetic and pharmaceutical ingredients conventionally used in the skin care industry that can be used as additional ingredients in the compositions for the present invention, as long as they are physically and chemically compatible with the other ingredients of the composition and especially with the active ingredients of the present invention. Also, the nature of these additional ingredients should not unacceptably alter the benefits of the active ingredient of the invention. These additional ingredients can be synthetic or natural such as plants extracts or issued from a bio-fermentation process.

Further skin care actives that are particularly useful combined with the composition can be found in Sederma's commercial literature and on the website www.sederma.fr, in Croda's commercial literature and on the website www.croda.fr.

Commercially available actives widely used in cosmetic compositions can also be mentioned as examples: betain, glycerol, Actimoist Bio 2™ (Active organics), AquaCacteen™ (Mibelle AGCosmetics), Aquaphyline™ (Silab), AquaregulK™ (Solabia), Carciline™ (Greentech), Codiavelane™ (Biotech Marine), Dermaflux™ (Arch Chemicals, Inc), Hydra'Flow™ (Sochibo), Hydromoist L™ (Symrise), RenovHyal™ (Soliance), Seamoss™ (Biotech Marine), Essenskin™ (Sederma), Moist 24™ (Sederma), Argireline™ (commercial name of the acetyl hexapeptide-3 from Lipotec), spilanthol or an Acmella oleracea extract known under the trade name Gatuline Expression™, a Boswellia serrata extract known under the trade name Boswellin™, Deepaline PVB™ (Seppic), Syn-AKE™ (Pentapharm), Ameliox™, Bioxilift™ (Silab), PhytoCellTec™Argan (Mibelle), Papilactyl D™ (Silab), Preventhelia™ (Lipotec), or one or more of the following active ingredients sold by Sederma : Subliskin™, Venuceane™, Moist 24™, Vegesome Moist 24™, Essenskin™, Juvinity™, Revidrat™, Resistem™, Chronodyn™, Kombuchka™, Chromocare™, Calmosensine™, Glycokin factor S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide H03™, Legance™, Intenslim™, Prodizia™, Beautifeye™, Pacifeel™, Zingerslim™, Meiritage™, Sebuless™, Apiscalp™, Rubistem™, Citystem™, Neonyca™, NG Insaponifiables de Beurre de Karite™, Majestem™, Hydronesis™, Poretect™, Amberstem™, Synchrolife™, or mixture thereof. Among plant extracts (in the form of classical plant extracts or prepared by an in vitro process) can be used as additional actives, there may more particularly be mentioned extracts of Ivy, for example English Ivy ( Hedera helix), of Bupleurum chinensis, of Bupleurum falcatum, of arnica (Arnica montana L), of rosemary ( Rosmarinus officinalis N.), of marigold ( Calendula officinalis), of sage ( Salvia officinalis L), of ginseng ( Panax ginseng), of gingko biloba, of St.-John's-Wort ( Hyperycum perforatum), of butcher's- broom ( Ruscus aculeatus L), of European meadowsweet ( Filipendula ulmaria L), of big- flowered Jarva tea ( Orthosiphon stamincus Benth.), of artichoke ( Cynara scolymus), of algae ( Fucus vesiculosus), of birch (Betula alba), of green tea, of cola nuts (Co/a nipida), of horse-chestnut, of bamboo, of Centella asiatica, of heather, of fucus, of willow, of mouse-ear, of escine, of cangzhu, of Chrysanthellum indicum, of the plants of the Armeniacea genus, Atractylodis platicodon, Sinnomenum, pharbitidis, Flemingia, de Coleus as C. forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C. barbatus, such as the extract of root of Coleus barbatus, extracts of Ballote, of Guioa, of Davallia, of Terminalia , of Barringtonia, of Trema, of Antirobia, Cecropia, Argania, Dioscoreae such as Dioscorea opposite or Mexican, extracts of Ammi visnaga, of Siegesbeckia, in particular Siegesbeckia orientalis, vegetable extracts of the family of Ericaceae, in particular bilberry extracts (Vaccinium angustifollium) or Arctostaphylos uva ursi, Aloe vera, plant containing sterols (e.g., phytosterol), Manjistha (extracted from plants of the genus Rubia, particularly Rubia cordifolia), and Guggal (extracted from plants of the genus Commiphora, particularly Commiphora mukul), kola extract, chamomile, red clover extract, Piper methysticum extract (Kava Kava™ from Sederma), Bacopa monieri extract (Bacocalmine™ from Sederma) and sea whip extract, extracts of Glycyrrhiza glabra, of mulberry, of melaleuca (tea tree), of Larrea divaricata, of Rabdosia rubescens, of Euglena gracilis, of Fibraurea recisa hirudinea, of Chaparral sorghum, of sun flower, d 'Enantia chlorantha, of Mitracarpe of Sperm acocea genus, of Buchu barosma, of Law sonia inermis L, of Adiantium capillus-veneris L, of Chelidonium majus, of Luffa cylindrica, of “Japanese Mandari” ( Citrus reticulata Blanco var. unshiu), of Camelia sinensis, of Imperata cylindrica, of Glaucium Flavum, of Cupressus sempervirens, of Polygonatum multiflorum, of Loveyly hemsleya, of Sambucus nigra, of Phaseolus lunatus, of Centaurium, of Macrocystis pyrifera, of Turnera diffusa, of Anemarrhena asphodeloides, of Portulaca pilosa, of Fiumuius lupulus, of Coffea arabica, of Ilex paraguariensis, or of Globularia cordifolia, of Oxydendron arboretum, of Albizzia julibrissin, of Zingimber zeru bet smith, of Astragalus membranaceus , of Atractylodes macrocephalae, of Plantago lanceolata, of Leontopodium alpinum (or edelweiss), of Mirabilis jalapa, of Apium graveoiens, of Marrubium vulgare, Buddleja davidii Franch, Syringa vulgaris or orchids.

The compositions of the present invention may include other peptides than the preferred peptides mentioned above, including, without limitation, di-, tri-, tetra-, penta-and hexapeptides and their derivatives. According to a particular embodiment, the concentration of the additional peptide(s), in the composition, ranges from 1x10⁷% and 20%, preferably from 1x10⁶% and 10%, preferably between 1x10⁵% and 5% by weight.

The term “peptide" refers here to peptides containing 10 amino acids or less, their derivatives, isomers and complexes with other species such as a metal ion (e.g., copper, zinc, manganese, magnesium, and others). The term "peptides" refers to both natural peptides and (bio)synthetic peptides. It also refers to compositions that contain peptides and which are found in nature, and/or are commercially available.

Suitable dipeptides for use herein include but are not limited to Carnosine (bAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM or PP.

Suitable tri peptides for use herein include, but are not limited to RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KbAK, KAbuK, KAcaK, KPK, KMOK, KMO2K (MO2 being a di-oxygenated sulfoxide methionine), KVK, PPL, PPR, SPR, QPA, LPA or SPA. Mention may also be made of non-limiting examples of tripeptides comprising: a lysine with its lateral chain grafted with a proline as K(P)HG or K(P)GH, K(P); a lysine with its lateral chain grafted with a pyroglutamic acid as K(Pyr)HG or K(Pyr)GH, K(Pyr); a lysine with the amine function of the lateral chain acetylated as K(Ac)HG or K(Ac)GH, K(Ac); a lysine with its lateral chain grafted with a hydroxyproline K(Hyp)HG or K(Hyp)GH, K(Hyp) as disclosed in WO2016/097965.

Suitable non limitative examples of tetrapeptides are KTFK (SEQ ID NO: 1), GQPR (SEQ ID NO: 2), RSRK (SEQ ID NO: 3), KTAK (SEQ ID NO: 4), KAYK (SEQ ID NO: 5), KFYK (SEQ ID NO: 6), or TKPR (SEQ ID NO: 7). A suitable non limitative example of pentapeptide is KTTKS (SEQ ID NO: 8) and KTSKS (SEQ ID NO: 9) and examples of hexapeptides are GKTTKS (SEQ ID NO: 10) and VGVAPG (SEQ ID NO: 11).

Other suitable peptides for use according to the present invention can be selected, this list being not limitative, from: lipophilic derivatives of peptides, preferably palmitoyl (Pal) derivatives or myristoyl (Myr), and metal complexes as aforementioned (e.g., copper complex of the tripeptide HGG or GHK). Preferred dipeptides include for example N-Palmitoyl^-Ala-His, N-Acetyl-Tyr-Arg-hexadecylester (Calmosensine™, Idealift™ from Sederma), Pal-RT or Pal-KT (from Sederma). Preferred tripeptide derivatives include for example Pal-GKH and Pal-GHK (from Sederma), the copper derivative of HGG (Lamin™ from Sigma), Lipospondin (N-Elaidoyl-KFK) and its analogs of conservative substitution, N-Acetyl-RKR-NH2 (Peptide CK+), N-Biot-GHK (from Sederma), Pal-KAvaK, Pal-^AIaK, Pal-KAbuK, Pal-KAcaK, or Pal-KM0₂K (Matrixyl®synthe’6® from Sederma), Pal-KVK (Syn-Coll™ of DSM), and derivatives thereof.

Mention may also be made here of the anti-aging tripeptides of general Formula X-Pro*-Pro*-Xaa-Y described in WO2015181688 application with Xaa selected from Leu, Arg, Lys, Ala, Ser, and Asp, at the N-terminus , X chosen from H, -CO-R¹ and -SO2-R¹ and at the C-terminal end Y chosen from OH, OR¹, NH2, NHR¹ or NR¹R², R¹ and R² being, independently of one another, chosen from a alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfurized, said group possibly possessing in its backbone a heteroatom particularly O, S and/or or N, and Pro* corresponding to Proline, an analogue or derivative thereof; comprising, for example, Myr-PPL-OH and Myr- PPR-OH.

Here can further be cited also the propigmenting and/or pro-mec dipeptides and tripeptides of general Formula X-(Xaai)n-Pro*-Xaa2-Y disclosed in WO2014/080376, with n=0, 1 or 2, Xaai an hydrophobic aminoacid selected from Ala, Val, Met, Leu, Iso, Phe, Pro, and analogs and derivatives thereof; or a polar aminoacid selected from Ser, Thr, Tyr, Asp, Glu and analogs and derivatives thereof; and when n=2 the two aminoacids Xaai being the same or different; Xaa2 being an hydrophobic aminoacid selected from Ala, Val, Met, Leu, Iso, Phe, and analogs and derivatives thereof, or a basic aminoacid selected from Arg, Lys, His, and analogs and derivatives thereof; at the N terminal end X being selected from H, -CO-R1 and -SO2-R1; at the C terminal end Y being selected from OH, OR1, NH2, NHRi or NR1R2; Ri and R2 being, independently from each other, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy et aryloxy group, that can be linear, branched, cyclic polycyclic, saturated, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, said group having or not an 0, S and/or N heteroatom in its skeleton and Pro* corresponding to a Proline, analog or derivative thereof; comprising for example the following peptides Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPA-OH, Myr-SPA- OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

Suitable tetrapeptides derivatives for use as additional peptides according to the present invention include, but are not limited to, Ela-KTAK (SEQ ID NO: 12), Ela-KAYK (SEQ ID NO: 13), Ela-KFYK (SEQ ID NO: 14), Pal- GQPR (SEQ ID NO: 15) or Pal-KTFK (SEQ ID NO: 16).

Suitable pentapeptides derivatives for use as additional peptides herein include, but are not limited to,

Pal-KTTKS (SEQ ID NO: 17) (MATRIXYL™, Sederma), Pal-KTSKS (SEQ ID NO: 18), Pal-YGGFXaa (SEQ ID NO: 19) with Xaa being Trp, Phe, Tyr, Tic, 7-hydroxy-Tic or Tpi, or mixtures thereof.

Suitable hexapeptides derivatives for use herein include, but are not limited to, Pal-HLDIIXaa (SEQ ID NO: 20) with Xaa being Trp, Phe, Tyr, Tic, 7-hydroxy-Tic or Tpi, Pal-GKTTKS (SEQ ID NO: 21), Pal-VGVAPG (SEQ ID NO: 22) (DERMAXYLT™, Sederma), or mixtures thereof The preferred compositions available commercially and sold by Sederma: tripeptides or a derivative include Biopeptide-CL™, Maxilip™, or Procapil™ containing GHK; tetrapeptides or a derivative include RIGIN™, Eyeliss™ containing Pal-GQPR (SEQ ID NO: 15) and an excipient, Crystalide™ containing Pal-KTFK (SEQ ID NO: 16) vehicle (solvated in microemulsion); pentapeptide or a derivative as Matrixyl ™ containing Pal-KTTKS (SEQ ID NO: 17).

Can also be mentioned:

- the mixture of Pal-GHK and Pal-GQPR (SEQ ID NO: 15) (Matrixyl™ 3000), and

- the mixture of Pal-GHK and Pal-VGVAPG (SEQ ID NO: 22) (Biobustyl ™).

The following marketed peptides can be mentioned as well as additional active ingredients:

Vialox™ (I NCI name = Pentapeptide-3 (synthetic peptide comprising alanine, arginine, isoleucine, glycine and proline)), Syn-ake™ (b-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys-Val-Lys-OH) marketed by Pentapharm;

Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (INCI name = Acetyl hexapeptide-3) (SEQ ID NO: 23), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 24), Aldenine™ (Gly-His-Lys), Trylagen™ (INCI name = Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline (reaction product of Citrulline and Tripeptide-10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine)), Tripeptide-1), Eyeseryl™ (Ac^-Ala-His-Ser- His)(SEQ ID NO: 25), Serilesine™ (Ser-lle-Lys-Val-Ala-Val) (SEQ ID NO: 26) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline = reaction product of Citrulline and Tripeptide-10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine) marketed by Lipotec;

Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO: 27)) or Quintescine™ (Cys-Gly) marketed by Vincience;

Cytokinol™LS (casein hydrolysate) marketed by Les Laboratoires Serobiologiques/Cognis;

- Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name = Monofluoroheptapeptide-1: reaction product of acetic acid and a synthetic peptide comprising arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan) marketed by Nnstitut Europeen de Biologie Cellulaire;

Neutrazen™ (Pal-His-D-Phe-Arg-NH2) marketed by Innovations; or

BONT-L-Peptide™ (INCI name = Palmitoyl Hexapeptide-19: reaction product of palmitic acid and Hexapeptide-19 (synthetic peptide constituted of asparagine, aspartic acid, lysine and methionine), Timp-Peptide™ (INCI name = Acetyl Hexapeptide-20: reaction product obtained by acetylation of Hexapeptide-20 (synthetic peptide constituted of alanine, glycine, lysine, valine and proline) or ECM Moduline™ (INCI name = Palmitoyl Tripeptide-28: reaction product of palmitic acid and Tripeptide-28 (synthetic peptide constituted of arginine, lysine and phenylalanine) marketed by Infinitec Activos.

It is also possible to envisage combining the invention with one or more cyclic peptides, in particular those extracted from linseed oil described in the Applicant's patent application FR1850845.

Zerumbone according to the invention or composition containing it can be preferentially combined with at least one compound chosen among vitamin B3, compounds as niacinamide or tocopherol, retinoids compounds as retinol, hexamidine, olipoic acid, resveratrol or DHEA, hyaluronic acid, peptides, in particular N-acetyl-Tyr-Arg- O-hexadecyl, Pal-VGVAPG (SEQ ID NO : 20), Pal-KTTKS (SEQ ID NO : 16), Pal-GHK, Pal-KM0₂K, Pal-GQPR (SEQ ID NO : 14) and Pal-K(P)HG (MATRIXYL™ Morphomics™, Sederma) that are classic active agents used in topical cosmetic or dermo-pharmaceutical compositions. Preferably, tetrapeptide(s) according to the invention combined with Ac-YR-hexadecyl ester peptides (IDEALIFT™, Sederma), Pal-GHK and/or Pal-GQPR (SEQ ID NO: 14). a) Example for obtaining a zerumbone extract for the invention implementation

Plant: Zingiber zerumbet (L.) Smith.

Part of the plant: dried and crushed roots (rhizomes).

Protocol: C0₂ subcritical or supercritical extraction

Extraction pressure: 70-1000 bars, preferably 70-350 bars.

Temperature: 10-100°C, preferably 20-70°C.

Duration: 24 to 48 hours.

Purification (filtration, centrifugation, crystallization). b) Galenic

An example of a galenic formulation is given below containing zerumbone as the active molecule. Furthermore, these formulations can also contain additional cosmetic active ingredients, the latter coming for each case in support and/or complement of the activity of the active ingredient according to the invention. These ingredients can be of any class according to their(s) function(s), site of application (body, face, neck, chest, hands, etc ), the desired end effect and the target consumer, for example anti-aging, moisturizing, slimming, anti- redness, anti-stretch marks, etc.

Active ingredient of the invention: CO2 supercritical extract of Zingiber zerumbet (L.) Smith, prepared according to above example a), comprising between 0.2% and 0.5%, preferably approximately 0.35% (3500 ppm) in weight of zerumbone based on the total weight of the ingredient in a butylene glycol matrix.

Preferably, formulations will contain between 0.5% and 5% in weight based on the total weight of the formulation for a final dosage of zerumbone between 0.001% (10 ppm) and 0.025% (250 ppm) in weight based on the total weight of the formulation.

Additional ingredients given as examples, that can be added alone or in combination.

Example: Cream Table 1:

Protocol

Mix phase A. Add phase B to phase A, mix. Add phase C to A+B, mix. Mix phase D, then add phase A+B+C, mix. Examples of additional ingredients that can be added to this formulation (sold by Sederma):

VENUCEANE™: active ingredient comprising a Thermus thermophiles biotechnological extract, that prevents visible signs of photo-aging (spots, wrinkles, dryness . ), protects cell structures from damages caused by UV and strengthens skin integrity; AQUALANCE™: osmoreceptor moisturizing active ingredient; CALMOSENSINE™: soothing active.

2) In vitro tests a) Akt and ERK phosphorylated Principle

Akt, ERK-1 and ERK-2 phosphorylated cause the inactivation of the cellular protein MITF, responsible from the synthesis of tyrosinase. Thus, this influences the reduction of melanin quantity produce.

Protocol

Mouse pigment cells called B16, and Normal Human Melanocytes (NHM), at confluence, were placed in contact with the product according to the invention. At the end of this contact period, the cells were rinsed, ground, the extracted and measured proteins by the bicinchoninic acid (BCA) method in order to standardize the quantity of proteins deposited on gels used to separate the extracted proteins by electrophoresis. B16 mouse pigment cells were placed in contact with the product according to the invention for 2 hours. NHM were placed in contact with the product according to the invention for 24 hours. The MITF and TRP1 proteins (on NHM) were revealed using antibodies specific for these proteins. For the phosphorylated forms of Akt, ERK-1 and ERK-2, specific antibodies recognizing the new form of these proteins were used.

In both cases, Labelling, followed by image analysis, were performed to determine the relative quantity of each protein studied and/or its phosphorylation, linked to the effect of a product, compared to a control without product b-actin labelling ensured the homogeneity of the deposits. Results

Table 2:

Effect of zerumbone according to the invention on Akt, d'ERK-1 and d'ERK-2 phosphorylated, in B16 mouse cells (n=3); after 2hours:

These results show that the Akt, d'ERK-1 and d'ERK-2 phosphorylated are significantly increased by 6 ppm of the product according to the invention compared to the control case, +335% (p<0.01) and +35.3% (p<002) respectively.

Table 3: Effect of zerumbone according to the invention on MITF, in mouse B16 cells, and on TRP1, in NHM (n=3); after 24hours:

These results show that the MITF activity in B16 mouse cells and TRP1 activity in NHM are strongly reduced by 6 ppm of the product according to the invention compared to the control case, -77.9% and -55.7% respectively

(p<0.01). The results of the reduction of melanin production in the two cell systems studied (NHM and B16 mouse cells) shows a good degree of similarity.

The mechanistic study shows that Akt phosphorylation is increased, as is that of ERK-1 and ERK-2. These phenomena are known to reduce the transcriptional activity of MITF or to activate its degradation. This leads to a reduction in the production of tyrosinase (visible by the reduction in its overall activity in both cell systems) and of TRP1 on NHM, and leading to a decrease in the production of melanin. b) Reduced PGE2 production Principle

PGE2, produce by many cells (keratinocytes, fibroblasts, melanocytes, etc.) regulates certain functions of the melanocyte, as the stimulation of the formation and extension of dendrites or the tyrosinase activity. Reduce the presence of PGE2 therefore reduces the melanin quantity transferred from the melanosome to the keratinocytes. Protocol

Human keratinocytes and Normal Human Fibroblasts (NHF), at confluence, were placed in contact with the product according to the invention for 24 hours. After this contact period, their medium was replaced with a buffer and the cells were irradiated with UVB to promote PGE2 synthesis. The cells were then placed in contact with the product according to the invention for another 24-hour period, the media were then harvested to measure the quantity of PGE2 released by these cells. The cell nuclei were stained using the Hoechst 33258 dye to estimate the number of cells and to standardize the results.

Results Table 4:

Effect of zerumbone according to the invention on PGE2 production, by NHF and keratinocytes (n=3):

These results show that the UV-induced PGE2 synthesis in NHF and keratinocytes is strongly reduced by 5 ppm of the product according to the invention compared to the control case, -89% and -66% (p<0.01) respectively. c) Reduced tyrosinase activity and melanin production Principle

Tyrosinase activity and melanin production are linked to both mechanisms mentioned above (phosphorylation of Akt, ERK-1 and ERK-2, as well as PGE2 synthesis). Phosphorylation increase and PGE2 synthesis decrease leads to a decrease in tyrosinase activity and melanin production, responsible for skin pigmentation.

Protocol Mouse pigment cells called B16, were cultured, then they were in contact with the product according to the invention for 2 days. Cell numbers did not vary significantly in all cases, as the product was neither toxic nor did it activate multiplication.

At the same time, NHM were cultured, and they were in contact with the product according to the invention for 10 days. The culture media were changed every 2-3 days to provide these cells with the necessary nutrients for their survival and metabolism. At the end of this contact, photographs were taken of the cell mats. Next, the mats were ground, and melanin was extracted from the cells. The quantity of melanin was assessed by spectrophotometry at 490 nm, using a standard range established previously from a melanin solution and compared to the control. A protein assay using the BCA method was performed to estimate the quantity of cells and to standardize the data obtained.

Results

Table 5: Effect of zerumbone according to the invention on melanin production and tyrosinase activity, in B16 mouse cells (n=4):

These results show that the melanin production and tyrosinase activity by B16 mouse cells is strongly reduced by 6 ppm of the product according to the invention, -67% and -49% respectively (p<0.01).

Table 6: Effect of zerumbone according to the invention on melanin production and tyrosinase activity, in NHM (n=4):

These results show that the melanin production and tyrosinase activity in NHM is strongly reduced by 2 ppm of the product according to the invention, -28.6% and -29.0% respectively (p<0.01). No cytotoxicity was observed

Claims

1 Use of zerumbone, derivative and/or analog thereof, or of a plant extract containing it, for a cosmetic non-therapeutic treatment, adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fade and/or make hyperpigmented areas on the skin disappear.

2 Use according to claim 1, characterized in that the non-therapeutic cosmetic treatment is a topical treatment.

3. Use according to claim 1 , characterized in that the zerumbone, derivative and/or analog thereof, or of a plant extract containing it, is adapted to act on the phosphorylation of Akt, ERK-1 and ERK-2 metabolic pathways, reduce PGE2 production and/or reduce tyrosinase production and melanin.

4. Use of zerumbone, derivative and/or analog thereof, or of a plant extract containing it, for the preparation of a cosmetic composition adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fade them and/or to make the hyperpigmented areas on the skin disappear.

5. Cosmetic composition containing between 0.000001% (0.01 ppm) and 15% (150000 ppm) of zerumbone or a plant extract containing it, based on the total weight of the composition, and a physiologically acceptable medium, adapted to prevent the appearance of hyperpigmented areas on the skin and/or adapted to fad and/or remove hyperpigmented areas on the skin.

6. Uses according to any of claims 1 to 4, or composition according to claim 5, characterized in that the zerumbone or the plant extract is derived from a plant of the Zingiberaceae family.

7. Use or composition according to claim 6, characterized in that the plant is Zingiber Zerumbet (L.) Smith.

8. Use or composition according to claim 6 or 7, characterized in that the solvent use for the extraction is a subcritical or supercritical fluid.

9. Use or composition according to claim 8, characterized in that the solvent use for the extraction is supercritical CO2.

10. A woven or non-woven material, comprising a composition according to any of claims 5 to 9, for prevent the appearance of hyperpigmented areas on the skin and/or for fade and/or make hyperpigmented areas on the skin disappear.