Extract of Cistus monspeliensis and compositions comprising same for soothing the skin

Abstract

The present invention relates to the use of an extract of Cistus monspeliensis in the treatment of sensitive skin, in particular in the treatment of neurogenic cutaneous inflammation and / or pruritus, in particular atopic dermatitis.

Description

Title of the invention: Extract of Cistus monspeliensis and compositions comprising it for soothing the skin TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to an extract of Cistus monspeliensis which may be useful in the protection and / or treatment of sensitive skin, atopic dermatitis, in particular by a combined action on cutaneous neurogenic inflammation and pruritus. The invention also relates to cosmetic or dermatological compositions comprising such an extract as an active agent. STATE OF THE ART

[0002] Cistus monspeliensis L. is a shrub from the Mediterranean region commonly called "Montpellier Cistus" or "Montpellier Rockrose". In France, it colonizes dry land, scrubland and garrigues on the Mediterranean coasts and in Corsica. The plant, glutinous, secretes a sticky and aromatic exudate. Its branches are erect and bear persistent, rough, sessile or subsessile leaves, linear-lanceolate or narrowly elliptical, three-veined, with revolute margins. The inflorescences are in unilateral scorpioid cymes composed of flowers 2 to 3 cm in diameter, with 5 white petals, never spotted with purple. The fruits are rounded capsules, easily crushed by finger pressure (Source: TISON J.-M. 2014, Flora Gallica - Flore de France. Biotope Editions, 1195).

[0003] Montpellier rockrose is one of the so-called "pioneer" plants. Its adaptability and resistance to poor soils, salt, and drought allow it to colonize degraded land in Mediterranean coastal areas and slow down their erosion. It often establishes itself in former cultivated land or abandoned pastures.

[0004] Several traditional uses of Cistus monspeliensis L. are referenced in the Mediterranean region, notably topically. In Morocco, the leaves are used in the form of poultices applied to wounds, as an antidiarrheal and for its anti-inflammatory properties. The use of Montpellier rockrose as an infusion, as a spice or in cases of asthma is reported (Demetzos et al., 2001, Planta Medica 67: 614-618). Extracts of Cistus monspeliensis L. are also found in several anti-aging cosmetic references.

[0005] The aerial parts of Cistus monspeliensis L. contain labdane-type diterpenes, among which 8-hydroxylabdan-15-oic acid or manoyl oxide may be mentioned. Clerodane-type diterpenes are also documented, such as 15-acetoxy-cis-clerodan-3-ene-18-oic acid (Papaefthimiou et al., 2014, Frontiers in Chemistry 2(35): 1-19).

[0006] Cistus monspeliensis L. also contains several families of polyphenols including flavanoids, tannins, in particular ellagic tannins, and phenolic acids (Santagati et al., 2008, Journal of Chromatography Science 46(2): 150-156).

[0007] The aerial parts of Cistus monspeliensis L. are also a source of essential oil whose major constituents are of the terpenic and phenolic type (Loizzo et al, 2013, Food and Chemical Toxicology 59:586-594).

[0008] Different extracts of Cistus monspeliensis L. have been the subject of in vitro and in vivo pharmacological studies. The antimicrobial and antifungal properties are documented (Bouamama et al., 2006, Journal of Ethnopharmacology 104: 104-107) as is the anti-Leishmania activity carried by the diterpenes of Montpellier Cistus (Fokialakis et al., 2006, Biological and Pharmaceutical Bulletin 29(8): 1775-1778).

[0009] The antioxidant activity of a methanolic extract of Cistus monspeliensis L. was demonstrated in tubo with in particular an IC50 of 3 pg / ml on a DPPH (2,2-diphenyl 1-picrylhydrazyl) test. The antioxidant activity of an aqueous extract, its protective activity with respect to DNA cleavage, and its inhibitory activity on lipid peroxidation have also been shown. Furthermore, the antioxidant activity of Cistus monspeliensis L. essential oil has also been documented in a study aimed at evaluating its interest in the prevention of neurodegenerative diseases (Loizzo et al., 2013).

[0010] In vitro, an inhibitory action of the alpha-glucosidase and alpha-amylase enzymes of aqueous and hydro-methanolic extracts of Cistus monspeliensis L. has also been demonstrated, linking the plant to a potential hypoglycemic activity (Sayah et al., 2017, BioMed Research International, 2789482: 1-7).

[0011] It has been reported that hexane and aqueous extracts of Cistus monspeliensis L. have antiproliferative activity on different cell lines (Angelopoulou et al., 2001, Planta Medica, 67(2): 168-202), ex vivo myorelaxant activity has been demonstrated with an aqueous extract of Cistus monspeliensis L. (Attaguile et al., 2004, Journal of Ethnopharmacology, 92: 245-250).

[0012] An anti-inflammatory activity of aqueous and ethanolic extracts of leaves of Cistus monspeliensis L. has been revealed on different early and generic markers of inflammation on in vitro tests on human cells (Taila et al., 2008, Journal of Pharmacie and Pharmacology, Suppl 1: A-62, 158).

[0013] The anti-inflammatory and analgesic properties of an aqueous extract of the aerial part of Cistus monspeliensis L. have been demonstrated in vivo by administration oral administration to mice and rats (Sayah et al., 2017, South African Journal of Botany, 113:160-163). Interestingly, analgesic activity is achieved after oral administration in conventional animal pain models such as the acetic acid injection writhing test.

[0014] Extracts of Cistus monspeliensis L. have been the subject of patent applications for cosmetic use, particularly in the field of anti-aging. Patent FR2819718 cites the extract of Cistus monspeliensis among lipid extracts intended for cosmetic use to combat skin aging. Patent FR2868307 discloses an extract of Cistus monspeliensis in the treatment of wrinkles associated with muscle contractions. Patent JP2011162504 cites that an extract of Cistus monspeliensis induces ATP production. Patent application GB2443388 describes a combination of hydrolyzed algin with at least one extract of Lavandula stoechas, He-lichrysum italicum and Cistus monspeliensis obtained by microwave-assisted vacuum hydrodistillation in the topical treatment of acne.

[0015] Finally, patent application WO 2020128223 relates to new cosmetic and dermatological uses of an extract of Cistus monspeliensis in maintaining or strengthening the barrier function, in particular by maintaining or increasing cell differentiation. The effects disclosed in this patent application only concern healthy skin, with so-called sensitive, pathological skin such as atopic skin or skin affected by dermatitis being explicitly excluded.

[0016] Thus, to the applicant's knowledge, no prior art document discloses that an extract of Cistus monspeliensis L., let alone an extract of the aerial parts of this plant, has an activity in the protection and / or treatment of sensitive skin, of atopic dermatitis, in particular by a combined action on neurogenic cutaneous inflammation and pruritus.

[0017] The skin constitutes a barrier against external attacks, in particular chemical, mechanical or infectious.

[0018] The skin is made up of three main parts, the superficial one, the epidermis, the internal part, the dermis and a deeper layer, the hypodermis, which interact.

[0019] The natural human epidermis is composed mainly of three types of cells which are keratinocytes, which are the vast majority, melanocytes and Langerhans cells. Each of these cell types contributes through its own functions to the essential role played in the body by the skin, in particular the role of protecting the body from external aggressions.

[0020] The dermis provides the epidermis with a solid support. It is also its nourishing element. It is mainly made up of fibroblasts within an extracellular matrix composed mainly of a substance, called ground substance, also containing collagen and elastin. These components are synthesized by the fibroblasts. Leukocytes, mast cells and tissue macrophages are also found there. Finally, the dermis is crossed by blood vessels and nerve fibers, including free sensory fibers or those connected to sensors.

[0021] Finally, the hypodermis is the deepest and thickest layer of the skin. It is a continuation of the dermis without any real separation between the two tissues. The hypodermis constitutes a shock-absorbing cushion that acts as mechanical protection for the underlying structures. This fatty layer also helps insulate the body from thermal variations. If the dermis can be considered a water reserve, the fats stored within the adipocytes of the hypodermis constitute an energy reserve.

[0022] A dysfunction of the epidermal cellular structural organization, or a defect in the chemical barrier function of the epidermis, can result in a cutaneous inflammatory state.

[0023] Inflammatory dermatoses are conditions of the skin and mucous membranes, often painful, which are characterized by unsightly manifestations such as redness and scaling patches. Several pathologies are grouped under the name of inflammatory dermatoses. Examples which may be cited, but are not limited to: atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigo, seborrheic dermatitis and acne.

[0024] Pruritus can be observed in many skin dermatoses, we speak of pruritic dermatoses such as atopic dermatitis, contact dermatoses, psoriasis, lichen planus, and ectoparasitoses and insect bites.

[0025] Atopic dermatitis is the cutaneous manifestation of atopy. It is a chronic inflammatory dermatosis, occurring on a genetically determined terrain. It affects 15 to 30% of children and 2 to 10% of adults. Its prevalence is constantly increasing in industrialized countries, it has doubled or even tripled over the last three decades and it is now considered a major public health concern. Atopic dermatitis is often associated with other atopic disorders, such as allergic rhinitis and asthma. This condition most often appears during early childhood and is characterized by repeated eruptions over several years. It progresses in flare-ups interspersed with spontaneous remissions. The lesions are characterized by significant skin dryness associated with inflammatory manifestations: papular, vesicular, scaly and very pruritic erythematous eruptions. Histologically, atopic dermatitis is characterized, like many dermatoses, by an infiltration of lymphocytes, monocytes and eosinophilic polymorphonuclear cells around small vessels and capillaries; biochemically, it is characterized by the expression of cytokines such as Thymia Stromal Lym- phopoietin (TSLP), a major protein in triggering inflammation associated with atopic dermatitis. Furthermore, it has been

[0026] showed that chemokines, including interleukin 8 (IL8) and lipid mediators of inflammation such as prostaglandin 6KFla, are strongly involved in dermatoses such as atopic dermatitis and in chronic inflammatory diseases in general. Acne is a common skin pathology, resulting from inflammation of the pilosebaceous follicles due largely to the colonization of Cutibacterium acnes in the infundibulum (Dréno et al., JEADV 2018, 32 (Suppl 2) 5-14). Furthermore, it is also known that the Thl7 pathway is highly activated in lesions of patients with acne (Kelhala et al., PLOS One, 9(8): el05238, 2014).

[0027] Pruritus is defined as an unpleasant sensation that causes the need to scratch. The concept of pruriceptors, specific receptors that allow the perception of pruritus, has recently emerged, but their distinction from the family of nociceptive receptors remains debated. Indeed, these pruriceptors use intraepidermal fibers of the Aô type and especially those of the C type. They secrete neuropeptides: substance P, calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP). Recently, the role of proteases in the induction of pruritus has been clearly established. Indeed, their PAR-2 ​​receptor has been defined as a major pathway for the activation of pruritus. It has also been identified as an important player in many inflammatory skin pathologies or inflammatory dermatoses, particularly atopic dermatitis.

[0028] The involvement of new non-histaminergic pruritus cellular receptors, the "Mas-related G protein-coupled receptor" (MRGPR), has recently been demonstrated, which have been clearly identified as being involved in pruritus and inflammation.

[0029] Cutaneous neurogenic inflammation is defined as the induction and / or amplification of a primary inflammatory process by nerve endings, thus it is an inflammation of the skin induced by the activation of intra-epidermal nerve fibers which secrete neuropeptides such as substance P. Cutaneous neurogenic inflammation is particularly involved in sensitive skin, reactive intolerant skin and even in pruritic inflammatory dermatoses. Recently, the role of proteases (trypsin, cathepsin G, thrombin etc.) in the induction of pruritus has been clearly established. Indeed, their receptor PAR-2 ​​has been defined as the second major pathway of activation of pruritus. Intradermal nerve fibers interact directly or indirectly with skin cells and cells of the endocrine, lymphatic and immune systems. These communications led to the definition of a neuro-immuno-endocrine-cutaneous system.To function, this . system requires a common language made up of molecules of different natures, neurotransmitters, cytokines and growth factors. These molecules are synthesized and released by skin cells, resident and recruited immune cells, and intraepidermal nerve endings. Epidermal and dermal cells can also produce neurotransmitters, enzymes, neurotrophins, cytokines, chemokines, and growth factors. These mediators regulate cutaneous innervation and the inflammatory response. In the event of inflammation, immune cells in transit or constitutively present in the skin can become activated by the action of these mediators secreted by sensory nerve endings and skin cells. This process leads to a second wave of cytokine and neurotransmitter release, which generates an amplification loop of inflammation. A new concept has recently emerged, suggesting that keratinocytes are also major players in cutaneous neurogenic inflammation.Neurogenic cutaneous inflammation generated by neuropeptides is involved in the reactivity of sensitive skin and also intolerant skin. The concept of sensitive skin reflects the level of sensitivity of each individual's skin. While sensitive skin is possible at any age, it is extremely common among babies and the elderly. Babies' skin is about one-fifth the thickness of adult skin and is therefore extremely sensitive to chemical, physical, and microbial aggressions, as well as UV rays. The barrier function of adult skin, on the other hand, gradually weakens with age, in parallel with the slowing of metabolic processes. Aging skin gradually leads to a lipid deficiency, making it more easily irritated by alkaline substances such as soap.When the skin has a very low sensitivity threshold, meaning it reacts in an exacerbated manner to the slightest external aggression, we speak of intolerant skin, or even reactive intolerant skin. Intolerant skin is more vulnerable to external aggressions and is characterized by daily discomfort and high irritability. Certain signs, more or less marked, allow us to recognize it. Intolerant skin on the face, for example, presents redness and tingling. It feels tight, hot or itchy. It can also cause burning sensations. Intolerant skin generally has an allergic background and is therefore particularly sensitive to the components of cosmetic care. Sensitive skin is in fact skin prone to tingling, heating, tingling and itching, sometimes accompanied by redness.These feelings of discomfort appear in an exacerbated manner in reaction to stimuli that would not trigger irritation on normal skin. This hypersensitivity of the skin results from a reduction in its tolerance threshold. The more sensitive the skin, the lower its tolerance threshold and when the tolerance threshold is at its lowest, we speak of intolerant skin. This hyper-sensitivity can be explained by different factors: - An inflammatory reaction that develops upon contact with irritating chemical substances such as certain soaps, household detergents or pollution; the triggering threshold of these substances thus making it possible to evoke sensitive skin or intolerant skin. - An alteration of the barrier function of the epidermis. This phenomenon then promotes dehydration of the skin and especially the penetration of potentially irritating agents; - Psychological factors, such as stress; - Hormonal factors; - Physical factors such as the sun, temperature changes (hot / cold), wind, air conditioning, heating, hard water.

[0030] The object of the present invention is to meet these needs, that is to say to propose compositions which protect and / or improve the condition of sensitive skin, by reducing neurogenic cutaneous inflammation on the one hand and pruritus on the other hand. Summary of the invention

[0031] The present invention relates to an extract of Cistus monspeliensis for its use in the prevention and / or treatment of skin disorders linked to neurogenic cutaneous inflammation.

[0032] The present invention also relates to an extract of Cistus monspeliensis for its use in the prevention or treatment of cutaneous pruritus.

[0033] Finally, the present invention relates to a dermatological composition comprising as active ingredient an extract of Cistus monspeliensis, with at least one dermatologically acceptable excipient for its use in the prevention and / or treatment of skin disorders linked to neurogenic cutaneous inflammation.

[0034] Other aspects of the invention are as described below and in the claims. Definitions

[0035] In the present invention, the plant Cistus monspeliensis L. may be designated for short by the term Cistus monspeliensis.

[0036] By “extract of Cistus monspeliensis”, we mean in the present invention, the extraction product of all or part of the Cistus monspeliensis plant.

[0037] For the purposes of the present invention, the term "extraction product" means the product obtained after extraction of the plant or a part of the plant, with a solvent called extraction solvent, i.e. a product present in the extraction solvent which may then optionally be in a concentrated or dry form after partial or total evaporation of the extraction solvent. It may be a dry extract.

[0038] For the purposes of the present invention, the term “dry extract” means an extract free of extraction or carrier solvent, or containing only insignificant traces thereof. Such a dry extract thus contains only material from Cistus monspeliensis. It may also contain insignificant traces of extraction solvent.

[0039] By "approximately", it is meant, within the meaning of the present invention, that the value concerned may be lower or higher by 10%, in particular by 5%, in particular by 2%, more particularly by 1% than the indicated value.

[0040] For the purposes of the present invention, the term "moderately polar solvent" means a solvent chosen from the group consisting in particular of C1 to C5 alcohols, glycols such as propylene glycol, butylene glycol, butanediol, or pentylene glycol, glycerol, acetone, alkyl esters such as ethyl acetate, isopropyl acetate, triethyl citrate, water-miscible solvents (a hydro-alcoholic mixture or an acetone / water mixture, for example). This group also includes alternative solvents of the hydrotropic type (water-soluble amphiphilic molecules which, from a sufficient concentration, can extract moderately polar compounds as described in the characterization of the extract).

[0041] For the purposes of the present invention, the term "apolar solvent" means a solvent chosen, for example, from heptane, hexane, limonene, ethyl oleate, halogenated hydrocarbons (for example, chlorinated hydrocarbons C1 to C3 such as chloroform or dichloromethane), supercritical CO2, a mixture of supercritical CO2 and ethanol, and mixtures of these solvents. Mention may also be made of 100% bio-sourced solvents, such as, for example, EcoXtract LIPOCOS (Supplier Pennakem Europe).

[0042] For the purposes of the present invention, "supercritical CO2 extraction" means extraction with CO2 in a supercritical state, that is to say, under a pressure and a temperature higher than its critical point. The temperature must therefore be higher than 31°C and the pressure higher than 74 bar. In its supercritical phase, CO2 is a completely neutral, non-toxic, non-polluting, non-flammable solvent allowing the extraction of lipophilic compounds. The polarity of supercritical CO2 can be modified by the addition of a polar co-solvent such as ethanol in order to broaden the polarity range of the extracted molecules. Supercritical CO2 extraction thus constitutes a preferred alternative to petrochemical solvents such as hexane or heptane.

[0043] For the purposes of the present invention, the term "diterpene" means C20 compounds derived from the metabolism of 2E, 6E, 10E-geranyldiphosphate. The structure of diterpenes is very variable and dependent on their biogenesis.

[0044] By "labdane-type diterpene" is meant, within the meaning of the present invention, a class of diterpenes having a bicyclic skeleton to which is attached a chain 6 carbon atoms (cyclic or acyclic) which may or may not contain an oxygen atom.

[0045] For the purposes of the present invention, the term “topical application” means an application to the skin (including the scalp) and the mucous membranes.

[0046] For the purposes of the present invention, the term "cosmetically acceptable" or "dermatologically acceptable" means that which is useful in the preparation of a cosmetic or dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for cosmetic or dermatological use.

[0047] For the purposes of the present invention, the term “topical application” means an application to the skin (including the scalp) and / or the mucous membranes. DETAILED DESCRIPTION OF THE INVENTION

[0048] Surprisingly and unexpectedly, the inventors have demonstrated that an extract of aerial parts of Cistus monspeliensis L. has anti-pruritus and nociception pathway modulating activity. This extract is therefore particularly interesting in the prevention and treatment of inflammatory dermatoses, in particular pruritic inflammatory dermatoses, for example atopic dermatitis or psoriasis. More generally, the extract is particularly useful in the protection and / or treatment of sensitive skin.

[0049] The extract of Cistus monspeliensis useful in the context of the present invention may be as defined below. Cistus monspeliensis extract

[0050] In the context of the present invention, the extract of Cistus monspeliensis is obtained from one or more parts of the Cistus monspeliensis plant selected from the whole plant, the roots, the aerial parts, the leaves, the trichomes, the fruits, the flowers, and / or the stems.

[0051] Advantageously, the extract of Cistus monspeliensis is obtained from vegetative-stage aerial parts, flowered aerial parts or fruiting-stage aerial parts of the Cistus monspeliensis plant.

[0052] More advantageously, the extract of Cistus monspeliensis is obtained from flowered aerial parts of the Cistus monspeliensis plant.

[0053] The Cistus monspeliensis plant or part of the plant may be fresh or dried, whole, cut or ground and then subjected to an extraction step. Advantageously, the Cistus monspeliensis plant or part of the plant is dried and ground before being subjected to an extraction step.

[0054] In one embodiment of the invention, the ground dry plant may be wetted in water before extraction.

[0055] In a particular embodiment of the invention, the Cistus monspeliensis extract is obtained from a culture of Cistus monspeliensis cells.

[0056] According to a preferred embodiment of the invention, the extract of Cistus monspeliensis is an extract obtained by supercritical CO2 extraction, in particular an extract obtained by supercritical CO2 extraction with or without the addition of ethanol as cosolvent, of flowering aerial parts of the Cistus monspeliensis plant.

[0057] According to a preferred embodiment of the invention, the extract of Cistus monspeliensis according to the invention can be obtained by a process as described below.

[0058] A process for preparing an extract of Cistus monspeliensis useful in the context of the invention, comprises a step of extracting all or part of the Cistus monspeliensis plant using a moderately polar to apolar solvent, preferably an apolar solvent.

[0059] In one embodiment, the extraction solvent may be chosen from supercritical CO2 with or without ethanol co-solvent, hexane, heptane, agro-sourced solvents of the EcoXtract LIPOCOS type, ethyl oleate, ethyl acetate, isopropyl acetate, triethyl citrate, a C3 to C5 glycol, a C1 to C5 alcohol, an alcohol / water mixture, a hydrotropic solution or a mixture thereof.

[0060] Advantageously, it will be supercritical CO2 with or without ethanol co-solvent, or ethyl acetate.

[0061] Advantageously, it will be supercritical CO2 with or without ethanol co-solvent.

[0062] More advantageously, it will be supercritical CO2 with ethanol co-solvent.

[0063] Even more advantageously, this supercritical CO2 / ethanol mixture will be characterized by a supercritical CO2 / ethanol proportion of 70:30 to 99:1 (m / m).

[0064] And even more advantageously, the apolar solvent is a supercritical CO2 / ethanol mixture in the proportion 92:8 (m / m).

[0065] According to another particular embodiment, the extraction by supercritical CO2 is carried out at a temperature between 32 and 55°C, at a pressure between 200 and 600 bars. The plant weight / supercritical CO2 volume ratio can vary from 1 / 10 to 1 / 100, for a duration of 1 minute to 48 hours. The extraction can be repeated 2 to 3 times.

[0066] In another particular embodiment, at the end of the extraction, the extraction continues with supercritical CO2 alone in order to dry the plant.

[0067] According to another particular embodiment, the extract obtained is then filtered in order to recover a clear liquid phase free of particles. The liquid phase obtained can be more or less concentrated, up to the point of obtaining a dry extract.

[0068] In another embodiment, a support may be added during the step of concentration so as to obtain an extract containing from 1 to 80% by weight of dry extract. The support may be maltodextrin, lactose, silica, glycerin, a glycol, a vegetable oil, triethyl citrate, ethyl oleate, dicaprylyl carbonate, octyldodecanol, a hydrotrope, a water / solubilizer or water / surfactant mixture, or any other cosmetologically acceptable support which solubilizes the extract, preferably of bio-sourced origin such as for example bio-sourced glycols (1,2-pentanediol; 1,3-butanediol; 1,3-propanediol, etc.), esterified fatty acids and also hydrotropes such as for example alkyl glycosides (Sepiclear, Apyclean, APXC4, etc.).

[0069] According to a particular embodiment, the extract of Cistus monspeliensis can be decolorized, for example on activated carbon. Compositions

[0070] The extract of Cistus monspeliensis can be used to formulate cosmetic or dermatological compositions. Such compositions comprise at least one extract of Cistus monspeliensis as described above, with at least one cosmetically or dermatologically acceptable excipient. The cosmetic or dermatological compositions, in addition to the extract of Cistus monspeliensis and a cosmetically or dermatologically acceptable excipient, may also contain surfactants, complexing agents, preservatives, antioxidants (such as tocopherols), stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, colorants, matting agents, chemical or mineral filters, moisturizing agents, thermal waters, etc.

[0071] The compositions are in a form suitable for use by topical application. The cosmetic or dermatological compositions may thus be presented in the forms which are usually known for topical administration, that is to say in particular lotions, milks, emulsions, serums, balms, masks, creams, dispersions, gels, mousses, sprays, shampoos.

[0072] According to a particular embodiment of the invention, the dermo-cosmetic or dermatological composition, comprising at least one extract of Cistus monspeliensis as described above and at least one cosmetically or dermatologically acceptable excipient, comprises from 0.01 to 5% by weight, preferably 0.01 to 4% by weight, preferably from 0.02 to 2% by weight, more preferably from 0.02 to 1.5% of extract of Cistus monspeliensis, by weight of dry extract relative to the total weight of the composition. This % by weight of dry extract is understood to be exclusive of the weight of the possible drying support, if there is one, and only concerns the dry plant extract.

[0073] Uses of Cistus monspeliensis extract and compositions comprising a such extract

[0074] Hereinafter, the extract of Cistus monspeliensis may be as described in detail above.

[0075] Hereinafter, the term “composition” refers to a cosmetic or dermatological composition as described above.

[0076] Cistus monspeliensis extract is particularly useful for the protection and / or treatment of sensitive skin. Thus, the present invention relates to a Cistus monspeliensis extract or a composition comprising such an extract for its use in the protection and / or treatment of sensitive skin. Cistus monspeliensis extract or compositions comprising such an extract soothe(s) the skin and increase(s) skin comfort.

[0077] The term "sensitive skin" refers to skin exhibiting increased non-immunological reactivity to normally well-tolerated physical or chemical stimuli. The increased reactivity is typically manifested by signs of skin discomfort, such as tingling, burning sensations, prickling, tightness, or itching.

[0078] Cistus monspeliensis extract reduces tingling sensations, burning sensations, tingling, tightness and / or itching of the skin. Thus, the present invention also relates to the use of a Cistus monspeliensis extract or a composition comprising it for reducing tingling sensations, burning sensations, tingling, tightness and / or itching. Cistus monspeliensis extract or a composition comprising it is particularly useful for the prevention and / or treatment of cutaneous pruritus. Thus, the present invention relates to a Cistus monspeliensis extract or a composition comprising such an extract for use in the prevention and / or treatment of cutaneous pruritus.

[0079] The invention relates in particular to an extract of Cistus monspeliensis or a composition comprising such an extract for its use in the prevention and / or treatment of skin disorders linked to / induced by cutaneous neurogenic inflammation. In other words, the extract of Cistus monspeliensis or a composition comprising such an extract can be used in the prevention and / or treatment of cutaneous neurogenic inflammation. Examples of skin disorders linked to / induced by cutaneous neurogenic inflammation include inflammatory dermatoses, such as psoriasis, acne and atopic dermatitis.

[0080] Thus, the extract of Cistus monspeliensis or a composition comprising such an extract can be used in the prevention and / or treatment of inflammatory dermatoses, in particular pruritic inflammatory dermatoses such as atopic dermatitis, contact dermatoses, psoriasis, lichen planus, ectoparasitoses and insect bites.

[0081] The invention also relates to a dermatological method for the prevention and / or the treatment of skin disorders linked to / induced by neurogenic cutaneous inflammation, in particular inflammatory dermatoses, especially pruritic inflammatory dermatoses, comprising administering to a person in need thereof an effective amount of an extract of Cistus monspeliensis or a dermatological composition comprising at least one extract of Cistus monspeliensis with at least one dermatologically acceptable excipient

[0082] The invention also relates to a cosmetic or dermatological method for the protection and / or treatment of sensitive skin, in particular in the case of atopic dermatitis, in particular by reducing neurogenic cutaneous inflammation and / or by reducing pruritus, comprising administering to a person in need thereof an effective amount of an extract of Cistus monspeliensis or a cosmetic or dermatological composition comprising at least one extract of Cistus monspeliensis with at least one cosmetically or dermatologically acceptable excipient.

[0083] The following examples illustrate the invention without limiting its scope. EXAMPLES Example 1: Supercritical CO2 extraction

[0084] 300 grams of crushed dry flowering aerial parts of Cistus monspeliensis are extracted by supercritical CO2 at a pressure of 250 bars and a temperature of 40°C at a flow rate of 10 kg / h for 180 minutes. After expansion to atmospheric pressure and return to room temperature, the installation is rinsed with ethanol to recover all of the extract. The extract is filtered on a K900 filter plate and the ethanol is evaporated to obtain 34 grams of a greenish wax with a mass yield of 11%.

[0085] Example 2: extraction by supercritical CO^ with ethanol co-solvent

[0086] 300 grams of crushed dry flowering aerial parts of Cistus monspeliensis are extracted by supercritical CO2 with 96° ethanol co-solvent at a pressure of 200 bars and a temperature of 40°C at a flow rate of 10 kg / h in CO2 and 0.8 kg / h in 96° ethanol for 180 minutes. After expansion to atmospheric pressure and return to room temperature, the extract is filtered on a K900 filtration plate and the ethanol is evaporated to obtain 35 grams of a greenish wax with a mass yield of 12%.

[0087] Example 3: extraction by supercritical CO with ethanol co-solvent and decolorization with activated carbon

[0088] 5 kilograms of crushed dry flowering aerial parts of Cistus monspeliensis are extracted by supercritical CO2 with 96° ethanol co-solvent at a pressure of 200 bars and a temperature of 40°C at a flow rate of 10 kg / h in CO2 and 0.8 kg / h in 96° ethanol for 180 minutes. After expansion to atmospheric pressure and return to At room temperature, the extract is filtered through a K900 filter plate and then decolorized with activated carbon (0.2% w / v solution). After further filtration through K900, the ethanol is evaporated to obtain 524 grams of an orange wax with a mass yield of 10%.

[0089] Example 4: extraction by supercritical CO2 with ethanol co-solvent and decolorization with activated carbon and placement on a fluid support

[0090] 10 kilograms of crushed dry flowering aerial parts of Cistus monspeliensis are extracted by supercritical CO2 with 96° ethanol co-solvent at a pressure of 200 bars and a temperature of 47°C at a flow rate of 40 kg / h in CO2 and 3.2 kg / h in 96° ethanol for 7 hours. After expansion to atmospheric pressure and return to room temperature, the extract is filtered on a K900 filtration plate then decolorized with activated carbon (0.5% w / v of solution). After further filtration on K900, the extract is dried on 1,2-pentanediol to obtain 5 kg of extract in the form of an orange viscous liquid. Example 5: Hexane extraction

[0091] 20 grams of crushed, dry, fruiting aerial parts of Cistus mons peliensis are extracted at room temperature with stirring by 200mL of hexane for 1 hour in a reactor. The extract is then filtered on a K900 filtration plate and the solvent is evaporated to obtain 2.2 grams of greenish wax with a mass yield of 11%. Example 6: evaluation of an extract of Cistus monspeliensis according to the invention in a model of TH 17 lymphocytes

[0093] It is now clearly known that the adaptive immune response plays a key role in the onset of psoriatic lesions and new treatments targeting interleukins IL-12, IL-23 or IL-17 show high clinical efficacy in patients with moderate to severe plaque psoriasis. Nevertheless, these systemic treatments remain restrictive and a topical approach still offers significant advantages: a perfectly limited treatment sparing the healthy perilesional skin, better skin hydration with protection against scratching, better patient acceptability and better tolerance. In addition, local treatments constitute the basis for the management of mild psoriasis, i.e. patients with involvement limited to less than 10% of the body surface area.

[0094] The aim of this study is to evaluate the potential activity of an extract of Cistus monspeliensis according to the invention to modulate the production of cytokines involved in psoriasis and atopic dermatitis. To do this, Thl7 lymphocytes isolated and amplified from the circulating blood of donors are used as an in vitro model of psoriasis immunopathogenesis.

[0095] Protocol:

[0096] The Cistus monspeliensis extract tested is prepared according to example 3 and was solubilized in DMSO (dimethyl sulfoxide) then placed in the culture medium of purified Thl7, at concentrations of 12.5; 25 and 50 pg / ml.

[0097] T lymphocytes are sorted from blood cells recovered from blood bags supplied by the French Blood Establishment, to obtain the following phenotype: CD4+ CD45RA- CXCR3- CCR6+. The number of Thl7 lymphocytes thus obtained is increased by culturing these cells in the presence of a mixture of cytokines (IL-2, anti-TNFa and anti-INFg) for two weeks.

[0098] The test is carried out on isolated and amplified human Thl7 lymphocytes in the absence (control conditions) or in the presence (treated) of the compounds to be tested and are stimulated or not by the anti-CD3 / anti-CD28 stimulation factors. The levels of pro-inflammatory cytokines of Thl7 (IL-17 and IL-22) are quantified 24 hours after stimulation. Lymphocytes are treated with the test compounds 30 minutes before stimulation and for 24 hours.

[0099] Nicardipine, a non-selective calcium channel blocker, was tested (10 pg / ml), also solubilized in DMSO, and is used as a positive control.

[0100] Each experimental condition was carried out in triplicate and repeated using blood from different donors.

[0101] Pro-inflammatory cytokines of lymphocytes Thl7, IL-17 and IL-22 are measured by ELISA kits according to the supplier's instructions.

[0102] Statistical analysis is determined on the percentage of inhibition after verification of normality and equality of variances, using a one-way ANOVA (ANnalysis Of Variance) followed by Dunnett's test as a post test. Results

[0103] The release of IL-17 (pg / ml) after treatment of Thl7 lymphocytes with anti-CD3 / anti-CD28 beads is shown in Table 1. These are so-called "coated" beads, on which the antibodies mentioned are fixed, in order to stimulate the lymphocytes.

[0104] [Tables 1] Groups Concentration IL-17 (mean) (pg / ml) Standard Error % Inhibition Stats VS. stim Control - 159 53 - P<0.001 Stimulation - 1187 109 - - Nicardipine lOpg / ml 721 63 43 P<0.001 Extract according to the invention 12.5pg / ml 537 187 58 P<0.001 25 pg / ml 671 42 47 P<0.01 50pg / ml 371 151 79 P<0.001

[0105] Table 1: effect of an extract of Cistus monspeliensis (extract according to the invention) on the production of IL-17

[0106] Exposure of Thl7 lymphocytes to anti-CD3 / anti-CD28 beads induces a marked and statistically significant increase in IL-17 release (Table 1). Nicardipine (100g / ml) reduces this IL-17 production by 43%. This result provides evidence of the good reactivity of the isolated and amplified Thl7 lymphocyte model, this result allows validation of the test.

[0107] Treatment of Thl7 lymphocytes with the Cistus monspeliensis extract according to the invention surprisingly shows an inhibition of IL-17 release. This inhibition appears statistically significant at the 3 concentrations tested, with nearly 80% inhibition at 50pg / ml of Cistus monspeliensis.

[0108] IL-22 release (pg / ml) after treatment of Thl7 lymphocytes with anti-CD3 / anti-CD28 beads is shown in Table 2.

[0109] [Tables2] Groups Concentration IL-22 (mean) (pg / ml) Standard Error % Inhibition Stats VS. stim Control - 92 16 - P<0.05 Stimulation - 945 357 - - Nicardipine lOpg / ml 440 88 37 NS Extract according to the invention 12.5pg / ml 252 72 51 NS 25 pg / ml 401 114 46 NS 50pg / ml 270 52 64 P<0.01

[0110] Table 2: effect of an extract of Cistus monspeliensis (extract according to the invention) on the production of IL-22 [YES] Exposure of Thl7 lymphocytes to anti-CD3 / anti-CD28 beads induced a marked and statistically significant increase in IL-22 release (Table 2). Nicardipine (100g / ml) reduced IL-22 production, but the inhibition did not reach the threshold of statistical significance. Indeed, in the stimulated group, a large variability of results was observed.

[0112] Treatment of Th 17 lymphocytes with the Cistus monspeliensis extract according to the invention also shows an inhibition of IL-22 release. Indeed, at a concentration of 50 pg / ml, the Cistus monspeliensis extract according to the invention significantly reduces IL-22 production by 64%. At lower concentrations, the inhibitory effect does not reach statistical significance, although the effect reaches 50%.

[0113] The inventors have thus shown that stimulated Thl7 lymphocytes induce a massive release of IL-17 and IL-22. In this model, the inventors demonstrate that an extract of Cistus monspeliensis according to the invention is very effective in limiting this release of inflammatory interleukins, a key marker in psoriasis, acne and atopic dermatitis, demonstrating a protective role in these pathologies, in particular through a soothing effect.

[0114] Example 7: evaluation of an extract of Cistus monspeliensis on the production of IL-8 and TSLP in a model of atopic dermatitis

[0115] The inventors evaluated the effects of a Cistus monspeliensis extract on cytokine production, induced by a mixture of inflammatory ligands on normal human epidermal keratinocytes. This inflammatory mixture is used to mimic the two phases of atopic dermatitis, namely the initiation phase and the chronic phase. In this model, the cytokine TSLP (Thymia Stromal LymphoPoietin), which plays a crucial role in the development of atopic dermatitis (Ziegler and Artis, 2010, Nat. Immunol. 11 (4): 289-293), is produced by this inflammatory mixture. 11-8 is also strongly induced by these conditions. The aim of this study is to evaluate the putative role of a Cistus monspeliensis extract in inhibiting the secretion of TSLP and IL-8.

[0116] The extract of Cistus monspeliensis was prepared according to example 3, it was tested at 3, 10 and 30 pg / ml, solubilized in 0.03% DMSO and placed in the culture medium of the kera-tonocytes.

[0117] Normal human epidermal keratinocytes are pre-incubated for 1 hour in a test medium containing or not (control) the compound to be tested or the reference product (Bafilomycin at 30 nM). These cells are then stimulated with the inflammatory mixture composed of Poly(I:C), PAM3CSK4, IL-4 and IL-13. Poly(I:C) is a TLR (Toll-Like Receptors) ligand, PAM3CSK4 is a TLR2 / TLR1 agonist, and IL-4 and IL-13 are two Th2 type interleukins.

[0118] A control, non-stimulated condition is also carried out in parallel.

[0119] The cells are then incubated for 24 hours.

[0120] Three independent experiments are carried out.

[0121] The culture supernatant is then removed, centrifuged and frozen at -20°C. TSLP and IL-8 production are quantified by ELISA, according to the supplier's instructions (R&D Systems).

[0122] Fluorescence detection is performed using the Flex station 3 system (Molecular Devices). Fluorescence quantification is done using the Soft Max Pro algorithm which provides Areas Under the Curve for each experimental condition.

[0123] All experiments are done in triplicate.

[0124] A statistical analysis is performed to evaluate the stimulated condition versus the untreated condition using an unpaired T-test. The inter-group comparison is made by a one-way ANOVA in repeated measures followed by a Dunnett post test. These statistical analyses are produced by PRISM software. Results

[0125] The results on TSLP production are summarized in Table 3.

[0126] Treatment of normal human epidermal keratinocytes with the inflammatory mixture induced a strong, statistically significant and reproducible production of TSLP. These results were expected and validate the test.

[0127] In the presence of DMSO (0.03%), TSLP production is statistically unaffected, showing that DMSO is not responsible for the observed effect.

[0128] [Tables3] Concentration Mean ± sem*(pg / ml) Inhibition (%) P Control - 4 + 2 - - Stimulation - 138 + 19 - - DMSO 0.03% 169 + 21 - NS Extract according to the invention 3pg / ml 121 + 14 29 NS lOpg / ml 99 + 9 42 P<0.05 30pg / ml 41+4 77 P<0.01

[0129] * sem: standard error of the mean

[0130] NS: Not significant

[0131] Table 3: effect of an extract of Cistus monspeliensis (extract according to the invention) on the TSLP production

[0132] When normal human epidermal keratinocytes are incubated in the presence of an extract of Cistus monspeliensis, the inventors demonstrate a concentration-dependent inhibition of TSLP production.

[0133] This inhibition appears statistically significant from the Opg / ml of Cistus monspeliensis. At 30pg / ml, Cistus monspeliensis extract reduces the production of TSLP induced by the inflammatory mixture by almost 80%.

[0134] The results on IL-8 production are summarized in Table 4.

[0135] Treatment of normal human epidermal keratinocytes with the inflammatory mixture induced a strong, statistically significant and reproducible production of IL-8. These results were expected and validate the test.

[0136] In the presence of DMSO (0.03%), TSLP production is statistically unaffected.

[0137] [Tables4] Concentration Mean ± sem* (pg / ml) Inhibition (%) P Control - 0 + 0 - - Stimulation - 36,780 + 4,146 - - DMSO 0.03% 39,842 + 3,844 - NS Extract according to the invention 3pg / ml 36,832 + 4,679 9 NS 10pg / ml 15,616 + 1,111 61 P<0.01 30pg / ml 1,599 + 283 96 P<0.01

[0138] * sem: standard error of the mean

[0139] NS: Not significant

[0140] Table 4: effect of an extract of Cistus monspeliensis (extract according to the invention) on the production of IL-8

[0141] When normal human epidermal keratinocytes are incubated in the presence of an extract of Cistus monspeliensis, the inventors demonstrate a concentration-dependent and very marked inhibition of the production of IL-8.

[0142] This inhibition appears statistically significant from 10pg / ml of Cistus monspeliensis. At 30pg / ml the extract of Cistus monspeliensis almost completely reduces (96% inhibition) the production of IL-8 induced by the inflammatory mixture.

[0143] The inventors therefore clearly demonstrate that an extract of Cistus monspeliensis is capable of strongly reducing the production of TSLP and IL-8 induced by a mixture of inflammatory ligands which mimics a dermatitis environment. atopic.

[0144] Thus the inventors demonstrate that an extract of Cistus monspeliensis has soothing and relieving effects in atopic dermatitis.

[0145] Example 8: evaluation of an extract of Cistus monspeliensis on receptors involved in the pruritus signaling pathway

[0146] The inventors evaluated the effects of a Cistus monspeliensis extract on two targets closely linked to pruritus, PAR-2 ​​and MRGPRX2.

[0147] PAR-2 ​​are G protein-coupled receptors. PAR-2 ​​modulates inflammatory responses, plays a role in obesity, metabolism and cancers. PAR-2 ​​acts as a sensor for proteolytic enzymes generated during infection. PAR-2 ​​is reportedly found in epidermal keratinocytes in the stratum granulosum layer. Functional PAR-2 ​​is also expressed in several immune cell types, such as eosinophils, neutrophils, monocytes, macrophages, dendritic cells, mast cells and T cells. PAR-2 ​​is activated by proteolytic cleavage by tryptase, which is the main protease of mast cells, and kallikrein, which is involved in inflammatory processes and epidermal homeostasis. Moreover, proteolytic cleavage of PAR-2 ​​induces calcium signaling if expressed in neurons participating in the afferent pathway.Activation of MRGPRX2 (Mast-Related G-Protein coupled Receptor) leads to degranulation of mast cells with subsequent pseudo-allergic reactions.

[0148] In order to determine the possible antagonistic or agonistic activities on these targets, these recombinant receptors were expressed in a heterologous model and coupled to a second messenger pathway.

[0149] The extract of Cistus monspeliensis was prepared according to Example 3, it was tested at ten concentrations ranging from 3.0 ng / ml to 100 pg / ml solubilized in DMSO.

[0150] The reference agonist for PAR-2 ​​is the peptide SLIGRL-NH2 with an EC50 value of 524 nM.

[0151] The reference agonist for MRGPRX2 is the neuropeptide Cortistatin-17 with an EC50 value of 269 nM.

[0152] Agonist and antagonist activities on human PAR-2 ​​and MRGPRX2 receptors were tested using Aequorin assays.

[0153] In order to validate the specificity of the observed antagonist activities, a first agonist activity was tested on the parental cell line, CHO-K1 mt aequorin, for all the compounds tested on these targets.

[0154] Recombinant cells were cultured for 18 hours prior to testing in antibiotic-free media, then detached by gentle rinsing with PBS-EDTA (5 mM EDTA), recovered by centrifugation, and resuspended in "buffer test". Cells were incubated at room temperature for at least 4 hours with luciferin: Coelenterazine h (Molecular Probes). Dose-response curves with the reference compounds were performed before testing the compounds.

[0155] For the agonist test, 50 μl of cell suspension were injected onto 50 μl of the test compound or reference agonist in a 96-well plate. After a 15-minute incubation following the first injection, 100 μl of the reference agonist at a concentration corresponding to its EC80 were injected onto the 100 μl of the mixture of cell suspension and test compound, for the antagonist test.

[0156] Three experiments (N = 3) were performed on different days in duplicate (n = 2).

[0157] The compounds were tested for their agonist and antagonist activity at the human PAR-2 and MRGPRX2 receptors in Aequorine-based assays.

[0158] The resulting light emission was recorded using the Hamamatsu Functional Drug Screening System 6000 (FDSS 6000).

[0159] The agonist activity of the test compounds was expressed as a percentage of the activity of the reference agonist at its EC100 concentration. The antagonist activity of the test compound was expressed as a percentage of the inhibition of the activity of the reference agonist at its EC80 concentration.

[0160] Each day of experimentation and before testing the compounds, the reference compounds were tested at several concentrations in duplicate (n=2) to obtain a dose-response curve and an estimate of the EC50 and / or IC50 values.

[0161] The reference values ​​thus obtained for the test were compared with the historical values ​​obtained for the same receiver and used to validate the experimental session.

[0162] A session was considered valid only if the reference value was within an interval of 0.5 log relative to the historical value. For repeated determinations, the maximum variability tolerated in the test was ±20% around the mean.

[0163] The dose - response data of the tested compounds were analyzed with the XLfit (IDBS) software using non - linear regression applied to a sigmoid dose - response model.

[0164] The agonist activity of the tested compounds is expressed as a percentage of the activity of the reference agonist at its EC50 concentration. The antagonist activity of the tested compound is expressed as a percentage of the inhibition of the activity of the reference agonist at its EC80 concentration.

[0165] Means and SEMs (standard error of the mean) were calculated with the data obtained from the three separate experiments. Results

[0166] PAR - 2 Activity

[0167] It was verified that the cistus monspeliensis extract showed neither activity on the parental line CHO-K1 nor agonist activity on the recombinant line CHO-K1 mt aequorin.

[0168] The results on the antagonistic activity of the cistus monspeliensis extract according to the invention on PAR-2 ​​are presented in Table 5.

[0169] [Tables5] Average % inhibition at maximum concentration IC50 (pg / ml) Individual value 90.5 26.8 96.7 21.2 97.1 14.0 Mean 94.8 + 2.1 20.7 + 3.7

[0170] The inventors thus clearly demonstrate that an extract of Cistus monspeliensis according to the invention exhibits antagonistic activity on PAR-2 ​​(IC50 of 20 pg / ml). MRGPRX2 activity

[0171] It was verified that the cistus monspeliensis extract did not exhibit activity on the parental line CHO-K1 nor agonist activity on the recombinant line CHO-K1 mt aequorin.

[0172] The results on the antagonistic activity of the cistus monspeliensis extract according to the invention on MRGPRX2 are presented in Table 6.

[0173] [Tableauxô] Average % inhibition at maximum concentration IC50 (pg / ml) Individual value 96.7 20.8 96.9 34.1 98.2 13.7 Mean 97.3 + 0.5 22.9 + 6.0

[0174] The inventors thus clearly demonstrate that an extract of Cistus monspeliensis according to the invention exhibits antagonistic activity on MRGPRX2 (IC50 of 23 pg / ml).

[0175] In this study, the inventors were able to demonstrate that an extract of cistus monspeliensis according to the invention had antagonistic properties on PAR-2 ​​and MRGPRX2 receptors, revealing a soothing effect, particularly in a pruritogenic context.

[0176] Example 9: evaluation of an extract of Cistus monspeliensis on a model of sensory neurons

[0177] The aim of this study is to evaluate the modulatory properties of a cistus monspeliensis extract in cutaneous neurogenic inflammation.

[0178] To do this, the inventors developed an in vitro experimental approach. An original model of human sensory neurons was developed after cellular reprogramming of human pluripotent stem cells. This model makes it possible to study the inhibitory properties of the release of substance P by the compounds to be tested, studied after stimulation. This neuropeptide, substance P, is the main neuromediator involved in the sensitization pathways in neurogenic inflammation, pain and pruritus.

[0179] The initial step is the reprogramming of human pluripotent stem cells by the successive use of different cocktails of growth factors. Phenotypic and morphological characterizations have allowed verification of the pattern of sensory neurons, particularly with the expression of specific receptors such as TrKA, 5HT-2, P2RX3 or channels such as TRPV1, Navl.7, Navl.8, TRPM8 with colocalization with neuronal markers (Tujl, Bm3A). These characterizations make it possible to establish a reprogramming duration to achieve an optimal pattern, which is between J40 and J47 after the start of treatments with the growth factor cocktail. Experimental conditions and treatment

[0180] The test is carried out on the model of sensory neurons in culture in a mixture of medium (RPMI / N2 / B27 / Glutamax) in the absence (control conditions) or in the presence (treated groups) of the products to be tested. These two conditions are tested in the presence of Veratridine or in its absence. Veratridine (tested at 3pM, diluted in DMSO, final molar concentration 0.006%) is a polycyclic alkaloid extracted from the rhizome of the lily Veratrum album. It causes persistent activation of voltage-dependent sodium channels. The levels of the neuropeptide substance P are quantified ten minutes after the addition of Veratridine.

[0181] The sensory neurons are treated for three hours with an extract of Cistus monspeliensis prepared according to Example 3, and tested at concentrations of 3 and 30 pg / ml in the best culture of the neurons, and for 10 minutes under stimulation (by Veratridine). Simultaneously, in another group, the sensory neurons are treated with lidocaine (a blocker of voltage-dependent sodium channels) at 100 pM (diluted in ethanol, final molar concentration 0.1%), used as a positive control. Each experimental condition is carried out on two separate batches of sensory neurons, and repeated at separate times between D40 and D47 in order to have experiments at n=2.

[0182] The released substance P is measured in the incubation media of the untreated group (control) and the treated groups after or without Veratridine stimulation. It is quantified by ELISA according to the supplier's instructions.

[0183] The level of substance P (pg / ml) is calculated by interpolation from a standard curve. Raw data and inhibition percentages are analyzed using Microsoft Excel and GraphPad Prism software. Data normality was assessed by Shapiro-Wilk and Kolmogorov-Smirnov normality tests. To validate the experiments, a paired Student t test is performed between unstimulated and stimulated conditions. Finally, to validate the activity of the reference compound and the test product, inter-group statistical comparisons are performed from the raw data by a one-way ANOVA associated with a Dunnett test as posttest. Results

[0184] Veratridine at 3 pM, as expected, strongly and significantly increases the release of substance P. Lidocaine, tested at 100 pM, significantly reduces the release of substance P induced by Veratridine stimulation. These results were expected, they allow this test to be validated.

[0185] The results of this release of substance P for all groups are summarized in Table 7.

[0186] [Tables?] Raw data Groups Concentration Mean ESM Control 47.67 16.71 Veratridine 96.26 19.66 Lidocaine 100pM 34.76 14.23 Cistus mons-peliensis extract 3 pg / ml 91.97 35.24 30pg / ml 44.83 8.31

[0187] The extract of Cistus monspeliensis tested at 3 pg / ml has no effect on the release of substance P, on the other hand at 30 pg / ml, it significantly reduces this release (P<0.05).

[0188] These results demonstrate the interest of an extract of Cistus monspeliensis according to the invention for modulating the nociception pathways.

[0189] With all of these results, the inventors demonstrate that an extract of Cistus monspeliensis according to the invention is useful in the treatment of atopic dermatitis thanks to its anti-pruritus action and modulator of nociception pathways. This extract of Cistus monspeliensis according to the invention is therefore particularly recommended for its soothing activity on sensitive skin.

Claims

Claims

1. Extract of Cistus monspeliensis for its use in the prevention and / or treatment of skin disorders linked to neurogenic cutaneous inflammation, the skin disorders being pruritic inflammatory dermatoses.

2. Extract of Cistus monspeliensis for use according to claim 1, wherein the pruritic inflammatory dermatosis is atopic dermatitis.

3. Extract of Cistus monspeliensis for use according to claim 1 or 2, characterized in that the extract of Cistus monspeliensis is obtained from the flowering aerial parts of the plant.

4. Extract of Cistus monspeliensis for use according to any one of claims 1 to 3, characterized in that the extract of Cistus monspeliensis is obtained by supercritical CO2 extraction, preferably with the addition of ethanol as co-solvent.

5. Cistus monspeliensis extract for use in the prevention or treatment of cutaneous pruritus.

6. Dermatological composition comprising as active ingredient an extract of Cistus monspeliensis, with at least one dermatologically acceptable excipient, for use in the prevention and / or treatment of skin disorders linked to neurogenic cutaneous inflammation, the skin disorders being pruritic inflammatory dermatoses.

7. A dermatological composition for use according to claim 6, wherein the pruritic inflammatory dermatosis is atopic dermatitis.

8. Dermatological composition for use according to claim 6 or 7, characterized in that the extract of Cistus monspeliensis is obtained from the flowering aerial parts of the plant.

9. Dermatological composition for use according to any one of claims 6 to 8, characterized in that the extract of Cistus monspeliensis is obtained by supercritical CO2 extraction.

10. Dermatological composition for use according to any one of claims 6 to 9, characterized in that the extract of Cistus monspeliensis is obtained by supercritical CO2 extraction with the addition of ethanol as co-solvent.

11. Dermatological composition for its use according to one of any of claims 6 to 10, characterized in that it comprises 0.01 to 5%, preferably 0.02 to 2% of Cistus mons-peliensis extract by weight of dry extract relative to the total weight of the composition.