FR3067594A1 - USE OF PLANT EXTRACTS FOR THE DERMATOCOSMAL TREATMENT OF INFLAMMATORY CONDITIONS RELATED TO OVERPRODUCTION OF IL-17 - Google Patents

Abstract

The subject of the present invention is the use of an arbutus extract or an aqueous rosehip extract for the treatment of pathologies associated with an overproduction of IL-17 chosen from: acne, psoriasis, vitiligo , rosacea, melasma, contact hypersensitivity and hidrosadenitis, especially to reduce inflammation of acne lesions.

Description

USE OF PLANT EXTRACTS FOR TREATMENT

DERMATOCOSMETICS OF INFLAMMATORY STATES LINKED TO A

OVERPRODUCTION OF IL-17

Field of the invention

The present invention relates to the use of plant extracts for the treatment of pathologies associated with an overproduction of IL-17, in particular inflammatory conditions associated with acne lesions. These extracts, which inhibit the effects of the cytokine IL-17 on the mechanisms of regulation of inflammation, prove to be promising for the treatment of inflammatory conditions of skin and acne lesions.

State of the art

Acne is an inflammatory pathology affecting the pilosebaceous follicle, affecting the face, chest and back. It is an extremely common disease which affects more than 80% of adolescents. In about 50% of people affected by juvenile acne, acne persists into adulthood. This dermatosis also affects infants and pregnant women. With the exception of the most severe cases, it is considered a simple physiological alteration, but it can enormously affect the quality of life of those who suffer from it. In most cases, acne is not an acute condition but a chronic condition, which therefore requires prolonged treatment. In this perspective, it is imperative that the treatments administered have minimal toxicity.

From a clinical point of view, acne is by definition a polymorphic condition which associates retentional lesions (microcysts, blackheads) and / or inflammatory lesions (papules, pustules or nodules). These two types of lesions can coexist or succeed each other during outbreaks.

The etiopathogenesis of acne is multifactorial. Factors playing a role in the development of acne are the increase in the production of sebum (hyperseborrhea) stimulated by the secretion of hormones and conditioned by a genetic predisposition, the obstruction of the pores due to an increase in keratinization follicular and sebum oxidation, proliferation of commensal bacteria of the pilosebaceous follicles Propionibacterium acnes.

Psoriasis is a common disease since it affects around 2% of the French population, and this at all ages. If it is mostly a mild illness, psoriasis can be a handicap that is difficult to live with on a daily basis and have a significant psychological impact.

Psoriasis is caused by chronic inflammation of the skin, for which the innate and adaptive immune systems are deregulated (Ariza et al., 2013). More particularly, it turns out that the dysfunction of the 11-17 axis is a major cause of the inflammatory condition characteristic of this skin pathology. This inflammation, evidenced by the presence in the skin of blood cells of the immune system (lymphocytes) leads to a runaway proliferation of epidermal cells, keratinocytes.

Instead of renewing itself in 28 days, keratinocytes renew themselves in 3 days. This accelerated renewal of the epidermis is accompanied by an abnormality of the cells which do not have time to properly finalize their normal maturation.

Contact hypersensitivity, or irritant dermatitis, is known to be the most common form of immunotoxicity encountered in humans (Kimble et al., 2002). By its allergic nature, this form of contact dermatitis is a hypersensitivity reaction that is atypical in the population. The mechanisms by which these reactions occur are complex, with several levels of control. Their immunological mechanism revolves around the interaction of the immunological regulation of cytokines, in particular IL-17 and TNF-a, and certain subpopulations of T lymphocytes.

Vitiligo manifests as white patches that correspond to areas of skin where the melanocytes have disappeared. Vitiligo plaques are generally asymptomatic.

The data concerning the involvement of the immune system are increasingly important. Studies have shown the role of the expression of certain cytokines such as 11-17, in vitiligo plaques but also in circulating blood. In addition, the levels of INF-α would be increased in the skins affected by vitiligo and in the immediate periphery (Webb et al., 2015).

Rosacea, also known as rosacea, is an incurable skin disease that starts off mildly and manifests itself as chronic redness in the nose, cheeks, sometimes also in the chin and forehead. These symptoms are accompanied by a tingling sensation, especially in the eyes. Small blood vessels, characteristic of spider veins are often visible in the affected areas associated with telangiectasia.

The disease is progressive and can cause acne attacks, especially in cases of stress or fatigue. When rosacea is at a more advanced stage, or subject to various factors, it can also severely affect the vision of the person affected by it (Gerber et al., 2011).

Melasma (also called chloasm or chloasma) is a benign dermatosis of the skin in the form of hyperpigmented spots appearing on areas exposed to the sun, especially in the face, neckline and neck.

Melasma affects mainly women, most often during pregnancy, giving what is commonly called the pregnancy mask, but it can appear outside of it.

Histological analysis has shown that this dermatosis is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells and fibroblasts. Dermal inflammation caused by ultraviolet radiation from the sun could play an important role in hyperpigmentation and the reactivation of melasma damage by the production of cytokines, such as IL-17 and TNF-α, and growth factors (Rodriguez -Arambula et al., 2015).

Hidrosadenitis, or Vemeuil disease, is a chronic skin disease causing the appearance of nodules, abscesses and inflammatory fistulas that affect areas with a certain type of sweat gland called apocrine (armpits, groin, buttocks, breasts) . This inflammatory skin pathology is mainly caused by cytokines such as IL-17 and TNF-α (Lima et al., 2016).

The general understanding of the inflammation associated with skin lesions, especially in the case of acne, is still fragmentary. Inflammation is however responsible for the redness which, although generally transient, is among the most unsightly and feared manifestations of this skin condition. In addition, the inflammation of acne lesions often causes post-inflammatory hyperpigmentation (HPI) which can persist over time and even prove to be permanent, in particular in dark phototypes (skin types IV-VI according to the classification of Fitzpatrick; Davis et al., 2010).

Acne scars can occur in forms where the inflammation is deep. They can take on the appearance of "microcraters" or, conversely, raised scars which correspond to fibrous changes in the skin. It is therefore desirable to treat the inflammation of acne lesions by acting on the cellular and tissue mechanisms regulating it in order to reduce redness, the formation of HPI and scarring.

Several therapies that are particularly effective in the treatment of acne are based on the anti-inflammatory properties of the drugs used, such as the administration of oral cyclins. Initially, these molecules were assigned an action on bacterial growth. However, it appears that cyclins exert their anti-inflammatory action through a reduction in the production of proinflammatory cytokines (Jain et al., 2002). However, the use of oral antibiotics is increasingly criticized because of the risks of inducing bacterial resistance to antibiotics. Alternatives to antibiotics are therefore necessary to treat inflammation of acne.

It is known that several inflammatory cell types are involved in the formation of inflammatory acne lesions: the infiltration of CD4 + T lymphocytes and macrophages precedes the formation of microcomedons (Jeremy et al., 2003). Polynuclear neutrophils are numerous in acne pustules, and are followed by the appearance of CD8 + T lymphocytes (Layton et al., 1998; Norris et al., 1988).

The cytokine IL-la plays a role in the initiation of microcomedons, because it triggers the induction of thickening of the stratum corneum (hyperkeratinization) (Guy et al., 1998; Jeremy et al., 2003).

The bacterial overgrowth of P. acnes also contributes to the inflammatory process of acne lesions, in which P. acnes acts through the activation of the TollLike Receptor 2 or TLR2 receptor (Dispenza et al., 2012). P. acnes triggers the activation of the oligomeric protein complex known as the inflammasome Nod-like receptor 3 or NLRP3, which leads to the synthesis of the proinflammatory cytokine IL-1 β by monocytes (Kistowska et al., 2014 ; Qin et al., 2014). Recent studies have shown that P. acnes could also play an important role in initiating the inflammatory reaction of the early phase of acne, through the activation of the synthesis of the cytokine IL-17.

IL-17 is a proinflammatory cytokine synthesized mainly by T lymphocytes. This cytokine induces the synthesis of cytokine IL-8, a cytokine involved in the recruitment of neutrophils. At the skin level, IL-17 is overexpressed in psoriatic inflammatory lesions (Cai et al. 2012). In vivo, the IL-17 pathway is activated in acne lesions (Kelhâlâ et al., 2014). Positive IL-17 T lymphocytes are found in the perifollicular infiltrates of comedones in the dermis (Kelhâlâ et al., 2014). P. acnes has been shown to stimulate the synthesis of the IL-17 isoform A in mononuclear cell cultures (Agak et al., 2014). The supernatants of P. acnes incubated with peripheral blood mononuclear cells (PBMC) induce their differentiation into LThl7 (Kistowska et al., 2015). In this study, it was observed that the supernatants of P. acnes can promote mixed Th 17 / Thl responses by inducing the concomitant secretion of IL-17A and IFN-γ by positive CD4 T lymphocytes (Kistowska et al., 2015 ), which confirms once again the proinflammatory role of this bacterium in the context of acne.

IL-17 targets neutrophils but also keratinocytes, endothelial cells, monocytes and fibroblasts to trigger a real proinflammatory cascade: when IL-17 binds to its receptor, it activates three transcription factors (NFkB, AP-1 and C / EBP) leading to the production of a battery of inflammatory mediators (in particular, iNOS, PGE2, GM-CSF, G-CSF and IL-8), which directly contribute to the activation of the system adaptive immune. In addition, IL-17 acts synergistically with TNFα in many situations, exacerbating the production of proinflammatory mediators (Miossec et al., 2012).

The suppression of the activity of IL-17 is therefore a target of choice for dermocosmetic treatments aimed at controlling the inflammatory manifestations without disturbing the balances of the skin and without resorting to broad-spectrum anti-inflammatory drugs, the use of which Systematic is neither desirable nor effective for the treatment of skin lesions, especially acne.

Applications WO2013 / 000869 and W02013 / 000870 describe new markers for the diagnosis of acne, methods of identifying inhibitors of IL-17 and the use of the inhibitors thus identified for the treatment of acne.

However, there is a permanent need to identify new dermocosmetic active agents with minimal toxicity and capable of acting on one or more of the mechanisms mentioned above.

Description of the invention

Surprisingly, the Applicant has shown that extracts obtained from the aerial parts of two plants make it possible to meet these needs, since they can inhibit the effects of IL-17 on human skin cells. These extracts are therefore of obvious interest in the prevention and treatment of pathologies associated with an overproduction of IL-17, in particular in the treatment of acne and its symptoms, and more specifically in the topical treatment of inflammatory conditions (inflammation and redness) acne lesions.

Thus, the subject of the present invention is the use of at least one plant extract chosen from an extract of strawberry tree and an extract of rose hips to treat pathologies associated with an overproduction of IL-17.

The invention also relates to a dermocosmetic composition for topical application containing at least one plant extract chosen from the group consisting of an extract of dog rose and an arbutus extract for its use in the treatment of pathologies associated with an overproduction of IL-17. .

According to another aspect, the invention relates to a method of cosmetic treatment of the skin and / or scalp having the symptoms of a pathology associated with an overproduction of IL-17 consisting in applying to the skin and / or to the leather a composition containing at least one plant extract chosen from the group consisting of an extract of dog rose and an extract of strawberry tree.

In the context of the present application, the term “IL-17” is understood to mean at least one of the cytokines of this family, including in particular IL-17A, IL-17B, IL-17C, IL-17D, IL17E, and IL-17F.

The expression "overproduction of IL-17" is understood to mean an increase in the level of expression and / or synthesis and / or activity of the cytokine or of its receptor, resulting in an over-activation of this pathway.

More specifically, the invention relates to a dermocosmetic composition for topical application containing at least one arbutus extract or an aqueous extract of rose hips for use in the treatment of pathologies associated with an overproduction of IL-17.

According to a particular embodiment, a pathology associated with an overproduction of IL-17 is chosen from the following group: acne, psoriasis, vitiligo, rosacea, melasma, contact hypersensitivity and hidrosadenitis, advantageously acne and in particular the inflammatory states of acne lesions.

The dog rose, also called dog rose, hedge rose or dog rose hips (Rosa canina), is a species of thorny shrubs of the Rosaceae family, very common in temperate regions of the Old World.

In practice, rosehip extract can be derived from any part of the rosehip plant.

In a particular embodiment, it is an extract of roots.

In a preferred embodiment, it is an extract of the aerial parts of the rosehip, advantageously chosen from the leaves, fronds, bark, flowers and fruits. Even more advantageously, it is an extract of the fruit of R. canina, also called rose hips.

In a particular embodiment, it is a lipophilic extract, that is to say, obtained using a lipophilic solvent, such as for example propanol or butanol.

Advantageously, it is an aqueous extract.

In another particular embodiment, the extract according to the invention is an ethanolic extract, that is to say that the solvent used is pure ethanol, or else a mixture of water and ethanol in variable proportions: for example, an ethanol / water ratio of 9: 1.4: 1, 2: 1, or 1: 1 can be used.

Alternatively, it is an extract obtained by using pure ethanol as a solvent, that is to say ethanol having a degree of purity equal to or greater than 99%. The ethanolic extract can include hydrophilic and lipophilic molecules.

In practice, following the extraction, the lipophilic or hydrophilic solvent is removed by evaporation and the extract is taken up in an appropriate storage solvent, for example, a mixture of water and propylene glycol.

According to a preferred embodiment, the rosehip extract is a hydrophilic extract, that is to say obtained using a hydrophilic solvent, such as, for example, a polyol or water.

Advantageously, it is an aqueous extract. By way of example, the rosehip extract according to the invention may correspond to the extract designated by the INCI Rosa canina fruit extract.

Preferably, the rosehip extract within the meaning of the invention represents from 0.0001% to 1% by weight of the composition, advantageously from 0.001% to 0.1% by weight of the composition, for example 0.05 %.

The strawberry tree (Arbutus unedo) is a species of shrub in the Ericaceae family common throughout the western Mediterranean rim, but also in the north of the eastern rim.

In practice, the strawberry extract can be obtained from any part of the strawberry plant.

In a particular embodiment, it is an extract of roots.

In an alternative embodiment, it is an extract of the aerial parts of the strawberry tree, advantageously chosen from the leaves, fronds, bark, flowers and fruits. In a preferred embodiment, this is a leaf extract.

According to another particular embodiment, it is a lipophilic extract, that is to say, obtained using a lipophilic solvent, such as for example propanol or butanol.

In another embodiment, the extract according to the invention is an ethanolic extract, that is to say that the solvent used is pure ethanol, or else a mixture of water and ethanol in variable proportions: for example, an ethanol / water ratio of 9: 1, 4: 1, 2: 1, or 1: 1 can be used.

Alternatively, it is an extract obtained by using pure ethanol as a solvent, that is to say ethanol having a degree of purity equal to or greater than 99%. The ethanolic extract can include hydrophilic and lipophilic molecules.

In practice, following extraction, the solvent is removed by evaporation and the extract is taken up in an appropriate storage solvent, for example, a mixture of water and propylene glycol.

In a preferred embodiment, the strawberry extract is a hydrophilic extract, that is to say, obtained using a hydrophilic solvent, such as for example a polyol or water.

Advantageously, it is an aqueous extract. By way of example, the strawberry extract according to the invention may correspond to the extract designated by the INCI Arbutus unedo leaf extract.

Preferably, the strawberry extract within the meaning of the invention represents from 0.0001% to 1% by weight of the composition, advantageously from 0.001% to 0.1% by weight of the composition, for example 0.05 %.

According to a particular embodiment, the composition of the invention contains a mixture of rosehip extract and strawberry extract. According to this embodiment, each plant extract within the meaning of the invention advantageously represents from 0.0001% to 1% by weight of the composition, advantageously from 0.001% to 0.1% by weight of the composition, for example 0, 05%.

According to another aspect, the composition of the invention also comprises at least one other active ingredient, advantageously known for the treatment of the targeted pathology, preferably chosen from:

dihydromyricetin, advantageously isolated and purified from the plant Myrica cerifera;

- a zinc salt, advantageously zinc gluconate;

- Biochanin A, advantageously obtained from an extract of red clover;

- an extract of Ginkgo biloba, advantageously comprising flavonoids;

- a meroterpene, advantageously bakuchiol;

a polyol, advantageously chosen from xylitol, rhamnose, sorbitol and mannitol;

- a lipophilic antioxidant, advantageously chosen from propyl gallate, octyl gallate and dodecyl gallate;

- a keratolytic agent, advantageously chosen from salicylic acid, glycolic acid, citric acid, malic acid, lactic acid and tridecyl salicylic acid, even more advantageously salicylic acid;

- an extract of licorice, advantageously comprising glycyrrhetinic acid and / or flavonoids;

- glycyrrhetinic acid, or one of its hydrophilic or lipophilic derivatives, or one of their salts;

- niacinamide or one of its derivatives;

- benzoyl peroxide;

- at least one tetracycline, advantageously chosen from the group consisting of clindamycin and / or erythromycin;

- at least one retinoid, advantageously chosen from the group consisting of tretinoin, isotretinoin and adapalene;

- butyl-hydroxytoluene (BHT);

- an extract from an ambora;

- an extract of green tea;

- N-palmitoyl-ethanolamide (PEA);

- lipids capable of restoring the skin barrier, advantageously cholesterol, squalane, skin triglycerides, skin free fatty acids and ceramides;

- a soy extract, advantageously an extract of bean sprouts titrated in genistein.

Dihydromyricetin (DHM, ampelopsin or ampeloptin [(2R, 3R) -3,5,7-trihydroxy-2 (3,4,5-trihydroxyphenyl) -2,3-dihydrochromen-4-one; CAS number 27200-12- 0) is a flavonol belonging to the group of flavonoids. Plants or plant extracts serving as a source of DHM are for example the plants Myrica cerifera, Ampélopsis spp., Cercidiphyllum japonicum, Hovenia dulcis, Rhododendron cinnabarinum, Pinus spp, Cedrus spp. and Salix spp.

In practice, DHM can be used in the composition of the invention in the form of purified or isolated DHM, preferably of purity at least equal to 60%, 70%, 80%, 90% or even at least equal to 95%. Alternatively, it can be in the form of a plant extract comprising DHM, advantageously representing from 1% to 70% by weight relative to the total weight of the extract.

According to a particular embodiment, the DHM is derived from an extract of the Myrica cerifera plant, in particular from the leaves, flowers or barks. According to a preferred embodiment, DHM is isolated and purified from the Myrica cerifera plant, such as for example the product titled DHM, sold by the company PROVITAL under the name TELOCAPIL SPE ™ or MYRICELINE ™.

Preferably, the DHM typically represents from 0.0001% to 10% by weight of the composition, advantageously from 0.001% to 2% by weight of the composition, even more advantageously 0.01% by weight of the composition.

Biochanin A (5,7-dihydroxy-3- (4-methoxyphenyl) -chromen-4-one; CAS number 491-80-5) is a flavonoid of interest, particularly for the treatment of acne.

Biochanin A is generally obtained from plants or plant extracts comprising this active ingredient. Plants or plant extracts serving as a source of biochanin A are for example Glycine max (soybean), Cicer arietinum (chickpea) Medicago sativa (alfalfa) or Trifolium pratense (red clover).

In practice, biochanin A can be provided by the addition of purified biochanin A, preferably having a degree of purity at least equal to 60%, or even at least equal to 70%, 80%, 90% or even at least equal to 95%, or by adding a plant extract comprising biochanin A. Extracts highly concentrated in biochanin A can be obtained, for example, using a mixture of propylene glycol and water to extract the hydrophilic fraction aerial parts of the above plants. The extracts thus obtained are subsequently clarified and subjected to sterilizing filtration.

According to a particular embodiment, the composition comprises a plant extract comprising biochanin A, preferably up to 0.1 g / L to 10 g / L of biochanin A relative to the plant extract.

According to one embodiment, the plant extract comprising biochanin A is an extract from the plant Trifolium pratense (red clover). Preferably, the plant extract comprising biochanin A is an extract from the aerial parts of red clover, advantageously from the leaves. In a particular embodiment, the extract comprising biochanin A is a titrated extract corresponds to the INCI Trifolium pratense (clover) leaf extract. By way of example, the hydroglycolic extract of red clover leaves marketed by the company GREENTECH can be used in the context of the invention.

Preferably, the extract comprising biochanin A represents from 0.001% to 1% by weight of the composition, advantageously from 0.01% to 0.1% by weight of the composition. In a particularly advantageous manner, the extract comprising biochanin A is a dry extract.

Zinc salts are known antibacterial agents and can help limit the proliferation of P. acnes and therefore reduce the inflammatory conditions of acne lesions later.

Advantageously according to the invention, the zinc is provided in the form of zinc salt 'S I making it possible to release the zinc in its ionic form Zn. Several zinc salts, alone or in combination, are suitable for use in compositions according to the invention.

Preferably, the zinc salt is chosen from zinc gluconate, zinc sulphate and zinc oxide. In a preferred embodiment, the zinc salt is zinc gluconate. According to a particular embodiment, the zinc salt is not a zinc oxide, moreover known for their use as sunscreens.

Preferably, the zinc salt represents from 0.1% to 10% by weight of the composition, advantageously from 1% to 5%, even more advantageously 1%, 2% or 3% by weight of the composition.

According to another aspect, the composition according to the invention comprises an extract of Ginkgo biloba.

Advantageously, the Ginkgo biloba extract is an extract of Ginkgo biloba comprising flavonoids, advantageously titrated in flavonoids. The extract of Ginkgo biloba is advantageously an extract of leaves. In a particular embodiment, the Ginkgo biloba extract corresponds to the INCI Ginkgo biloba leaf extract. By way of example, the glycolic extract of Ginkgo biloba leaves at 5% in dry matter marketed by the company GREENTECH can be used in the context of the invention.

Preferably, the extract of Ginkgo biloba represents from 0.0001% to 1% by weight of the composition, advantageously from 0.001% to 0.1% by weight of the composition.

According to another aspect, the composition according to the invention comprises a soy extract, advantageously an extract of soya bean titrated in genistein. In accordance with the teaching of FR 2 885 301, genistein is capable of inhibiting the secretion of the vasodilating epidermal factor Vascular Endothelial Growth Factor or VEGF, which makes it possible to reduce redness, in particular in subjects suffering from rosacea. Preferably, the soy extract represents from 0.01% to 5% by weight of the composition, advantageously from 0.1% to 2%. Thus, the ISOFLAVONE 40 raw material sold by the company ACS can be used as a source of genistein in the compositions according to the invention.

According to another aspect, the composition according to the invention comprises a meroterpene. Meroterpenes are also useful for reducing sebum oxidation and suppressing the activity of elastases and collagenases, enzymes involved in the formation of atrophic acne scars. Meroterpenes are also provided with an antimicrobial action, and can therefore limit the proliferation of P. acnes and thus reduce the inflammation of acne lesions.

Meroterpenes are generally obtained from plants or plant extracts. They can also be obtained from mushrooms or even be synthesized. Plants serving as a source for the meroterpenes are for example Psoralea coryfolia, Psoralea spp. and Otholobium pubescens.

In practice, meroterpene can be provided by the addition of isolated and purified meroterpene, preferably having a degree of purity at least equal to 60%, or even at least equal to 70%, 80%, 90% or even at least equal to 95%, or by adding a plant extract including meroterpene.

According to a preferred embodiment, the composition comprises a plant extract comprising meroterpene, preferably from 1% to 70% by weight of meroterpene relative to the total weight of the extract. The plant extract comprising meroterpene is advantageously a plant extract chosen from P. coryfolia, P. spp. and O. pubescens.

For example, the meroterpenes described in document WO2008 / 143761 and WO2008 / 140673 can be used in the context of the present invention.

According to a preferred embodiment, the meroterpene used in the context of the invention is bakuchiol.

Advantageously, the bakuchiol is provided by the addition of a plant extract comprising it, preferably an extract of seeds of P. coryfolia.

According to another embodiment, the bakuchiol is isolated and purified from the P. coryfolia plant, advantageously from its seeds, such as for example the product titrated in bakuchiol, sold by the company SYTHEON LTD under the name Sytenol®. In this product, bakuchiol has a purity greater than 95%.

Preferably, the meroterpene represents from 0.01% to 5% by weight of the composition, advantageously from 0.1% to 2% by weight of the composition, even more advantageously 0.25% by weight of the composition.

The composition according to the invention can also comprise a polyol, advantageously chosen from xylitol, rhamnose, sorbitol and mannitol, optionally as a mixture. Preferably, the polyol is xylitol.

The xylitol can be powdered xylitol, for example of vegetable origin, in particular obtained from wood by hydrogenation of xyloses, preferably having a purity greater than 95%. The mannitol can for example be powdered mannitol, of vegetable origin (corn, potato, wheat), preferably having a purity greater than 98%.

For example, the company IMCD markets the product Pearlitol® which can be used in the context of the invention.

Suitably, the polyol represents from 0.0001% to 10% by weight of the composition, advantageously from 0.001% to 2% by weight of the composition, even more advantageously from 0.005% and 1%, for example 0.1% by weight of the composition.

Advantageously, the composition according to the invention can also comprise a lipophilic antioxidant.

By way of example, the lipophilic antioxidants described in document FR 2 857 266 can be used in the context of the invention. The lipophilic antioxidant is preferably chosen from propyl gallate, octyl gallate and dodecyl gallate, advantageously propyl gallate.

According to one embodiment, the lipophilic antioxidant represents from 0.001% to 1% by weight of the composition, advantageously from 0.01% to 0.5% by weight of the composition.

According to another embodiment, the composition according to the invention comprises a keratolytic agent, preferably chosen from salicylic acid, glycolic acid, citric acid, malic acid, lactic acid and the acid salicylic tridecyl, preferably salicylic acid.

Preferably, the keratolytic agent represents from 1% to 10% by weight of the composition, advantageously from 2% to 8% by weight of the composition, even more advantageously 5% by weight of the composition.

According to another embodiment, the composition according to the invention comprises an extract of licorice, advantageously comprising glycyrrhetinic acid and / or flavonoids.

In practice, it may be an extract of Glycyrrhiza, preferably chosen from Glycyrrhiza uralensis, Glycyrrhiza inflata and Glycyrrhiza glabra.

According to a particular embodiment, it is an extract of roots.

Advantageously, the composition according to the invention comprises glycyrrhetinic acid or one of its derivatives (hydrophilic or lipophilic) or a salt thereof. Glycyrrhetinic acid is a soothing agent, useful for the treatment of inflammatory lesions in acne. In practice, the glycyrrhetinic acid can be provided by the addition of the purified compound, preferably of purity at least equal to 90%, or by the addition of a plant extract comprising it or titrated in this active.

For example, the raw material marketed by INDENA or MARUZEN under the name INCI glycyrrhetinic acid can be used in the context of the invention.

Advantageously, the glycyrrhetinic acid, or one of its derivatives or salts, or the liquorice extracts represents from 0.01% to 1% by weight of the composition, advantageously from 0.1% to 0.5 % by weight of the composition, even more advantageously 0.3% by weight of the composition.

The composition according to the invention may also comprise an effective dose of other active agents commonly used for the topical treatment of acne, such as for example niacinamide and its derivatives, benzoyl peroxide, at least one tetracycline, advantageously chosen from the group consisting of clindamycin and erythromycin, and / or at least one retinoid, advantageously chosen from the group consisting of tretinoin, isotretinoin and adapalene. In known manner, these molecules act as antimicrobial agents and / or as anti-inflammatories.

Preferably, the benzoyl peroxide and the tetracyclines individually represent from 0.1 to 15% by weight of the composition, advantageously from 1 to 10% by weight of the composition. Advantageously, the retinoid represents from 0.01 to 1% by weight of the composition, preferably from 0.05% to 0.1%.

Thus, vitamin B3 (also known as vitamin PP, niacinamide or nicotinamide) stimulates the synthesis of lipids of the stratum corneum, such as ceramides, and is provided with anti-inflammatory properties, which can prove useful in the treatment acne and other conditions listed.

Advantageously, the composition therefore contains vitamin B3 and / or one of its derivatives. By way of example of vitamin B3 derivatives, mention may be made of tocopheryl nicotinate or methyl nicotinate.

In practice, vitamin B3 and / or one of its derivatives preferably represent between 0.001% and 2% by weight of the composition, advantageously between 0.01% and 0.1%.

Ambora extracts (Drum issa trichophylla), as described in WO 2010/037545, can also be added to a composition according to the invention.

In practice, the ambora extract can represent between 0.00005% and 1% by weight of the composition, advantageously between 0.001% and 0.1%, even more advantageously 0.05%.

Preferably, the ambora extract is an extract from the leaves of the plant. Preferably, the ambora extract according to the invention is rich in polyphenols, advantageously rich in rutin, nicotiflorin, and / or epicatechin and in gallic acid polymers.

Advantageously, the total polyphenols of the ambora extract consist mainly of tannins of gallic acid. Preferably, the ambora extract according to the invention contains between 45% and 75% of polyphenols, by weight relative to the weight of the extract.

A suitable ambora extract is an extract corresponding to the INCI designation Tambourissa trichophylla leaf extract. By way of example, the product marketed by BAYER HEALTHCARE under the name ROSABORA can be used in the context of the invention.

Green tea extracts can also be added. The leaves of the tea plant (Camellia sinensis), especially those of green tea, contain more than 60% of polyphenols by weight of dry matter. Among the polyphenols of the flavanol class, there are more particularly catechins, such as catechin, epicatechin, epigallocatechin 3-O-gallate (EGCG). Preferably, the green tea extract is an extract of leaves from the tea plant.

Preferably, the green tea extract contains more than 15% of polyphenols of the catechin subfamily by weight relative to the weight of the extract, advantageously between 19% and 25%.

Preferably, the green tea extract comprises epigallocatechin 3-O-gallate, advantageously at least 13% of EGCG by weight relative to the weight of the extract.

The green tea extract according to the invention is, by way of example, an extract corresponding to the designation INCI Camellia sinensis leaf extract. By way of illustration, the product marketed by INDENA under the name of Greenselect® can be used in the context of the invention.

In practice, the green tea extract can represent between 0.00005% and 1% by weight of the composition, advantageously between 0.001% and 0.1%, even more advantageously 0.03%.

Among other compounds of interest which can be added to the composition of the invention, mention will be made in particular of butyl-hydroxytoluene (BHT), butyl-N-palmitoyl-ethanolamide (PEA), and lipids capable of restoring the barrier. skin.

PEA is well known to exert biological properties in relation to chronic pain and inflammation.

Advantageously, the composition of the invention also contains PEA. By way of example, the cosmetic raw materials having the designation INCI palmitamide MEA can be used in the context of the invention.

In practice, the PEA can represent between 0.1% and 1.0% by weight of the composition, advantageously 0.3%.

Advantageously, the cosmetic composition also comprises lipids capable of restoring the skin barrier, preferably natural constituents of the hydrolipidic film, advantageously chosen from the group consisting of cholesterol, squalane, skin triglycerides, fatty acids skin free and ceramides.

In an advantageous embodiment, the lipid capable of restoring the skin barrier is squalane.

The squalane is advantageously of plant origin. For example, the PHYTOSQUALAN® raw material sold by the company SOPHIM can be used in the context of the invention.

In practice, the lipids capable of restoring the skin barrier preferably represent between 0.1% and 5% by weight of the composition, advantageously between 1% and 3%.

In an advantageous embodiment, the composition according to the invention also contains at least one sunscreen. Within the meaning of the invention, the term "sun filter" includes organic and mineral compounds capable of filtering visible light, UV-A, UV-B and / or UV-C.

Examples of sunscreens, suitable for use in cosmetic compositions containing a plant extract within the meaning of the invention, are:

broadband filters, that is to say filters which absorb both UV-A and UV-B, such as filters corresponding to the INCI designations tris biphenyl triazine and bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbutylphenol, ethylhexyl triazone and diethylhexyl butamido triazone;

The organic UV filters liquid at room temperature, particularly advantageous within the meaning of the present invention, are the liquid filters at room temperature corresponding to the following INCI designations: homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl methoxycinnamate and isoamyl p20 methoxycinnamate, a- (trimethylsilyl) -œ- (trimethylsilyloxy) poly [oxy (dimethyl) silylene] -co- [oxy (methyl) (2- {4- [2,2bis (ethoxycarbonyl) vinyl] phenoxy} -1 -methyleneethyl) silylene] -co [oxy (methyl) (2- (4- [2,2-bis (ethoxycarbonyl) vinyl] phenoxy) prop-l-enyl) silylene], corresponding to the designation INCI polysilicone-15;

Inorganic mineral filters, in particular metal oxides and / or other compounds which are hardly soluble or insoluble in water, in particular the oxides of titanium (TiCL), zinc (ZnO), iron (FejOs), zirconium ( Ζ1Ό2), silicon (S1O2), manganese (for example MnO), aluminum (AI2O3), cerium (Ce2O3);

The UV-A filters in particular are the dibenzoylmethane derivatives, in particular the filters corresponding to the INCI designation Butyl methoxydibenzoylmethane and the filter corresponding to the INCI designation diethylamino hydroxybenzoyl hexyl benzoate;

Water-soluble filters, such as the filter corresponding to the designation INCI Disodium phenyl dibenzimidazole tetrasulfonate or the filter corresponding to the designation INCI Phenylbenzimidazole sulfonic acid.

The list of UV filters mentioned that can be implemented within the meaning of the present invention is of course given for information and not limitation.

In a preferred embodiment, the compositions according to the invention also comprise at least one sunscreen chosen from the group consisting of organic filters corresponding to the INCI designations tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl methoxycinnamate, diethylamino hydroxybenzoyl hexyl benzoate, butyl methoxydibenzoylmethane, disodium phenyl dibenzimidazole tetrasulfonate, phenylbenzimidazole sulfonic acid, as well as mineral filters corresponding to titanium oxides (TiO2), zinc oxides, ZnO).

The preparations according to the invention advantageously contain substances which absorb UV radiation in the UV-A, UV-B and / or UV-C range in a total amount, for example from 0.1% by weight to 30% by weight. weight, preferably 0.5 to 20% by weight, in particular 1.0 to 15.0% by weight, respectively relative to the total weight of the preparations, in order to provide cosmetic compositions which protect the skin or the integuments of the whole range of UV radiation.

Advantageously, these different ingredients are added, alone or in combination, in the concentration ranges mentioned above in relation to each of them.

Of course, any other active ingredient of cosmetic or pharmaceutical grade, having an activity of interest in the context of the applications targeted by the present application, can be incorporated into a composition according to the invention, such as vitamin derivative, lipophilic antioxidant, anti - broad spectrum inflammatory.

According to the invention, the composition is a cosmetic or dermatological composition, in other words is intended for cosmetic or dermatological use. Consequently and advantageously, all of the ingredients present in such a composition must be acceptable in these fields of application.

In view of the intended applications, a composition according to the invention is preferably intended to be applied topically, advantageously to the skin and / or scalp.

Thus and in a preferred manner, the composition according to the invention is in a form suitable for administration by the topical skin route: cream, emulsion, advantageously oil in water (O / W), water in oil (W / O) or water in silicone (I / O), solution, suspension, gel, milk or lotion, micellar water, preferably in the form of a cream, gel or lotion.

Consequently, the present composition may contain any additive or excipient suitable for its formulation and its application, such as, for example, suspending agents, emulsifiers, anionic, cationic or nonionic polymers, amphoterics, proteins, vitamins, surfactants, mineral or vegetable oils, antioxidants, waxes, gums, resins, thickening agents, acidifiers or alkalinizers, pH stabilizers, antiUV agents, filters and sunscreens, preservatives, perfumes, dyes, abrasives, conventional adjuvants in cosmetics and dermatology .

As already said, the composition according to the invention is particularly suitable for the treatment of skin pathologies associated with the presence of P. acnes. More generally, it is of interest in the care of subjects presenting at least one of the symptoms of acne, whatever its stage of development, or likely to develop it, in particular in subjects with oily skin and / or prone to acne.

According to another aspect, the invention therefore relates to a composition as described above for its use in the prevention and / or treatment of acne.

The composition of the invention can also be used in non-therapeutic applications, such as cosmetic applications, in particular those targeting oily skin or acne-prone scalps. Thus and according to another aspect, the invention relates to a cosmetic treatment process for oily or acne prone skin and / or scalp with acne prone consisting in applying to the skin and / or to the scalp a composition as defined above.

In the context of the present application and as will be illustrated below, interesting and novel properties of plant extracts according to the invention have been highlighted.

Examples of realization

The manner in which the invention can be implemented and the advantages which result therefrom will emerge more clearly from the following exemplary embodiments, given by way of non-limiting example, in support of the appended figures.

Legends of figures

Figure 1: Effect of rosehip and strawberry extracts and a positive inhibition control (dexamethasone ΙμΜ) on IL8 synthesis induced by IL-17 in combination with TNFα.

1 / Examples of formulation:

The quantities indicated are given in percentage by weight.

1-1 oil in water emulsion (O / W)

INC name /

Aqua / Water / Water

Propylheptyl caprylate

Dipropylene glycol

Glycerin____ _

Zinc gluconate___ _

Salicylic acid

Sodium hydroxide __

Arachidyl alcohol _

Behenyl alcohol

Glyceryl stearate

69.895

9,995

...... :::: ........... Z5oj ³ '°°

2.00

1.68

1,375

0.75

0.50

Peg-100 stearate 0.50 Silica 0.50 Xanthan gum 0.40 Arachidyl glucoside 0.375 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer 0.37 squalane 0,255 Bakuchiol 0.20 Glycyrrhetinic acid 0.20 Propylene glycol 0.164 Sodium metabisulfite 0.10 xylitol 0.10 Polysorbate 60 0,055 Arbutus unedo leaf extract 0.05 Ginkgo biloba leaf extract 0.016 Sorbitan isostearate 0,015 tocopherol 0.005

1-2 Gel

INCI name

Aqua / water / eau_ _ _

Glycolic acid_____

Zinc gluconate _____

Ammonium acryloyldimethyltaurate / vp copolymer Dipropylene glycol

92.008

2,002

2.00

1.00

1.00

Sodium hydroxide Hydroxyethylcellulose Stearyl glycyrrhetinate Mannitol

Propylene glycol Propyl gay late Rosa canina fruit extract Ginkgo biloba leaf extract

1-3 Lotion

INCI name

Aqua / Water / Water

Lactic acid

Peg-11 methyl ether dimethicone

Glycerin

Sodium citrate

Sodium hydroxide

Propylene glycol

Arbutus unedo leaf extract

Rosa canina fruit extract__

Ginkgo biloba leaf extract ___

0.80

0.70

0.20

0.10

0.082

2ξο | ι

Ζθϊ ^, Ι

0.008 ____ 91.7935

2.9865

2.00 ................ 1.50

ZLZZ the 0.50 · ⁰⁰ ___

0.164

0.02

ZZZZZZZ ° '° ² 0.016

II / Evaluation of the anti-inflammatory activity of rosehip extract and strawberry extract on the synthesis of IL-8 induced by IL-17 in normal human keratinocytes

The aim of the study is to evaluate the anti-inflammatory effect of rosehip extract and strawberry extract on inflammation (synthesis of IL-8) induced by IL-17 in association with TNF-α on keratinocyte cultures.

Π-l Materials and methods

Hacat human keratinocytes were used as a cellular model. The association of inflammatory cytokines IL-17 (30 ng / ml) and TNF-a (5 ng / ml) was used to induce the synthesis of IL-8 in keratinocyte cultures (Table 1). The inducer doses have been validated beforehand so as to have an optimal action of IL-17 on the induction of IL-8.

Table 1: IL-8 inducers tested in the study

inductors References Lots suppliers solutions mothers Conc. finals tested TNF- 300-01A 0906CY2 5 PreproTech 100 pg / ml 5 ng / ml IL-17 200-17-25UG 061184F0 815 PreproTech 100 pg / ml 30 ng / ml

The assay of IL-8 in keratinocyte supernatants was carried out using the Enzyme Linked Immunosorbent Assay kit (ELISA; Ref: DY208, R&D Systems, France),

24 hours after adding the inductors.

The doses of rosehip extract, arbutus extract and positive inhibition control tested are shown in Table 2.

Table_2: Assets tested and positive inhibition control

No commercial References Lot Stock solution (W / v) Dose tested in (W / V) Extract rosehip ROCC1410L1- AQSC - clean 2%, 0.66% and 0.22% Extract arbutus 900255 - clean 0.37%, 0.12% and 0.041% dexamethasone 9-fluoro- 11β, 17,21trihydroxy-16améthylprégnal, 4-diene-3,20 dione D8893 SLBN5236 V 0.1% ETOH 1 pM = 0.00004%

The effect of rosehip extract and strawberry extract on the viability of human keratinocytes (Hacat) was assessed by the MTT test after 24 hours of contact. The results represent the data obtained from an experiment with 3 wells per condition.

The results are expressed as a percentage of cell viability in Table 3 below.

Table 3: Effects of the active ingredients and controls on the viability of human keratinocytes (Hacat) evaluated by the MTT test

Condition tested (HACAT 24h) DO 540 nm Way do DO AND Viability (%) AND VIABIL ity No. l # 2 # 3 witnesses No treaty 2,882 2,796 2,707 2,803 0.059 100.0 2,088 2,827 2,825 2,779 Extract arbutus 1.10% 1,237 1,290 1,411 1,313 0.089 46.8 3.2 0.37% 3,285 3,397 3,348 3,343 0,056 119.3 2.0 Extract rosehip 2% 2,714 2,582 2,559 2,618 0.084 93.4 3.0 0.66% 2,672 2,624 2,776 2,691 0.078 96.0 2.8 0.22% 2,820 2,742 2,738 2,767 0,046 98.7 1.6 0.074% 2,954 3,025 2,974 2,984 0,036 106.5 1.3 0.024% 3,111 3,084 3,039 3,078 0,036 109.8 1.3

II-2 Results and discussion

The results of the effect of extracts of dog rose and strawberry tree and of a positive inhibition control (dexamethasone ΙμΜ) on the synthesis of IL8 induced by IL-17 in association with TNFa, are presented in FIG. 1 .

The "untreated" control corresponds to the level of inflammation in basal condition, without induction by a cytokine. No IL-8 synthesis is detected in this condition.

The condition "TNF-α 5ng / ml" represents the pro-inflammatory effect of this cytokine alone. It reveals a 62% induction of IL8 synthesis.

The condition "IL-17 30 ng / ml" represents the pro-inflammatory effect of this cytokine alone. It shows that only IL-17 does not induce synthesis of IL8.

The combination "IL-17 (30 ng / ml) + TNF-a (5 ng / ml)" arbitrarily represents 100% of inflammation induction. Under these conditions, there is a synergy of the pro-inflammatory effect of the two cytokines.

Dexamethasone 1 μΜ is the positive control for inhibition of inflammation. The association "IL-17 30 ng / ml + TNF-α 5ng / ml + Dexamethasone 1 μΜ" reveals a significant inhibition of 19.3% of the inflammation induced by the association of cytokines.

Rosehip extract, tested at 2%, 0.66% and 0.22%, induces a significant and dose-dependent inhibition of the inflammation induced by IL-17 30 ng / ml in combination with TNFα 5ng / ml, equal to 85%, 31.6% and 5.5%, respectively.

Likewise, the strawberry extract significantly inhibits the inflammation induced by IL17 at 30 ng / ml in combination with TNF-α at 5ng / ml. The inhibition induced is equal to 100%, 96.4% and 76.3 at the respective doses in extract of 0.37%, 0.12% and 0.041%. The inhibition induced is dose-dependent.

In conclusion, this study shows that the extracts of chosen rosehip and strawberry tree exert a significant, significant and dose-dependent inhibition on the synthesis of IL8 induced by IL-17 in association with TNF-α. The inhibition induced by these two extracts is greater than that induced by a very effective anti-inflammatory, the corticosteroid dexamethasone.

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Claims (8)

1 / Dermocosmetic composition for topical application containing at least one aqueous extract of dog rose for use in the treatment of pathologies associated with an overproduction of IL-17 chosen from: acne, psoriasis, vitiligo, rosacea, melasma, contact hypersensitivity and hidrosadenitis, advantageously acne. 2 / Composition for its use according to claim 1, characterized in that the extract comes from the aerial parts of the dog rose. 3 / Composition for its use according to one of claims 1 to 2, characterized in that the rosehip extract is derived from fruits. 4 / Composition for its use according to one of the preceding claims, characterized in that the extract represents from 0.0001% to 1% by weight of the composition, advantageously from 0.001% to 0.1% by weight of the composition . 5 / Composition for its use according to one of the preceding claims, characterized in that it also comprises at least one ingredient chosen from: dihydromyricetin, advantageously isolated and purified from the plant Myrica cerifera; a zinc salt, preferably zinc gluconate; biochanin A, advantageously obtained from an extract of red clover; an extract of Ginkgo biloba, advantageously comprising flavonoids; a meroterpene, advantageously bakuchiol; a polyol, advantageously chosen from xylitol, rhamnose, sorbitol and mannitol; a lipophilic antioxidant, advantageously chosen from propyl gallate, octyl gallate and dodecyl gallate; a keratolytic agent, advantageously chosen from salicylic acid, glycolic acid, citric acid, malic acid, lactic acid and tridecyl salicylic acid, even more advantageously salicylic acid; a licorice extract, advantageously comprising glycyrrhetinic acid and / or flavonoids; glycyrrhetinic acid, or a hydrophilic or lipophilic derivative, or a salt thereof; niacinamide or one of its derivatives; benzoyl peroxide; at least one tetracycline, advantageously chosen from the group consisting of clindamycin and / or erythromycin; at least one retinoid, advantageously chosen from the group consisting of tretinoin, isotretinoin and adapalene; butyl hydroxytoluene (BHT); an ambora extract; green tea extract; N-palmitoyl-ethanolamide (PEA); lipids capable of restoring the skin barrier, advantageously cholesterol, squalane, skin triglycerides, skin free fatty acids and ceramides. ; a soy extract, advantageously an extract of soybeans titrated in genistein; an arbutus extract, advantageously an aqueous extract, even more advantageously obtained from the leaves. 6 / Composition for its use according to one of the preceding claims, characterized in that it further comprises at least one sun filter chosen from the group consisting of organic filters corresponding to the INCI designations tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl methoxycinnamate, diethylamino hydroxybenzoyl hexyl benzoate, butyl methoxydibenzoylmethane, disodium phenyl dibenzimidazole tetrasulfonate, phenylbenzimidazole sulfonic acid, as well as mineral filters Z (oxides), their mixtures. 7 / Composition for its use according to one of the preceding claims, characterized in that it is in the form of a cream, a gel or a lotion. 8 / Composition for its use according to one of the preceding claims, characterized in that it is applied to oily or acne-prone skin, and / or to acne-prone scalp.