FR2967065A1 - Non-therapeutic cosmetic use of at least one pomegranate extract, as agent for preventing and/or treating dysesthetic sensations of skin and/or intolerant and/or irritable of scalps, and to treat sensation e.g. tingling - Google Patents

Abstract

Non-therapeutic cosmetic use of at least one pomegranate extract, as agent for preventing and/or treating dysesthetic sensations of skin and/or intolerant and/or irritable of scalps, is claimed. An independent claim is included for a composition comprising in a medium, the extract in association with at least one inhibitor of neuropeptides comprising a neuropeptide Y antagonist, an antagonist of substance P and calcitonin gene related peptide antagonist and/or a probiotic and/or a prebiotic and/or an inhibitor of nitric oxide (NO) synthase comprising an extract of plant of Vitis vinifera, a plant extract of Olea europaeaand an extract from a plant of Gingko bilobaand/or ingredient able to cause irritation such as a desquamating agent, surfactants, preservatives, detergents, perfumes, solvents, and/or propellants. ACTIVITY : Anabolic. MECHANISM OF ACTION : None given.

Description

The present invention is in the field of care of skin and / or intolerant and / or irritable scalp.

It relates in particular to the use of pomegranate extract for the prevention or treatment of dysaesthesic sensations of skins and / or intolerant and / or irritable scalps.

Human skin consists of two compartments, namely a deep compartment, the dermis and a superficial compartment, the epidermis. The epidermis is in contact with the external environment. One of its roles is to protect the body from dehydration and external aggression, particularly related to environmental factors like irritants or pollutants (detergents, pollution, cigarette smoke ...), mechanical stresses (friction, abrasion) , shaving, frequent washing ...), thermal or climatic imbalances (cold, wind, drought, UV radiation ...), xenobiotics (microorganisms, allergens ...), cosmetic or dermatological chemical treatments (peeling, anti-inflammatory treatment) Acne ...), or by physiological factors (age, stress ...). Some people have skin or scalp that are more intolerant or irritable than others. In general, intolerant or irritable skin is defined by a particular reactivity of the skin. However, as opposed to so-called allergic skins, this reactivity is not an immunological process, i.e. does not occur only on skin already sensitized in response to the presence of an allergen. Its mechanism is said to be nonspecific.

This cutaneous reactivity is conventionally translated by the manifestation of signs of discomfort in response to the contacting of the subject with a triggering element which may have various origins. It may be the application of a cosmetic product on the surface of intolerant or irritable skin, the taking of food, exposure to sudden variations in temperature, atmospheric pollution and / or ultraviolet or infrared rays. There are also associated factors like age and skin type.

The appearance of these signs of discomfort, which appear within minutes of contacting the subject with the triggering element, is one of the 40 essential characteristics of intolerant and / or irritable skin. It is mainly dysaesthetic sensations.

The term "dysaesthetic sensations" is understood to mean sensations felt in a cutaneous zone such as tingling, tingling, itching, sensations of warming, discomfort, tightness, etc. These subjective neurosensory signs most often exist in the absence of visible clinical signs such as redness. The sensation of heating or of heat that is felt is not necessarily linked to a real heat production at the level of the cutaneous zone concerned. It is now known that these irritation and cutaneous intolerance reactions are notably related to a release of neuropeptides (substance P, CGRP, VIP, POMC) by the nerve endings of the epidermis and the dermis.

The manifestations of the skin and scalp intolerant and / or irritable, within the meaning of the present invention, appear outside of any inflammation reaction. In particular, no swelling of the skin or scalp intolerant and / or irritable. In addition, the discomfort corresponding to dysaesthetic sensations, which may be one of the characteristics of these skins, can not be described as painful.

For obvious reasons, the absence of visible signs makes it difficult to diagnose these intolerant and / or irritable skins. Most often, this diagnosis is based on the interview of the patient. This symptomatology also has the advantage of making it possible to differentiate those skins associated or not with a dryness, irritation or contact allergy for which there are however visible inflammatory signs. Tools for evaluating the sensory reaction of the skin, well known to those skilled in the art, can also be used to carry out this diagnosis (for example the "stinging test" with lactic acid or the test with capsaicin) .

In the present description, unless it is specified differently, "skin" means the entire coating of the human body, that is to say the skin, mucous membranes and scalp.

An intolerant skin is a skin that reacts with sensations of heating, tugging, tingling and / or redness, to various factors such as the application of cosmetic or dermatological products or soap.

Irritable skin, otherwise known as reactive skin, is a skin that reacts with pruritus, that is to say itching or tingling, to various factors such as the environment, emotions, food, wind , friction, razor, hard water with high concentration of limestone, temperature variations or wool.

The term "intolerant and / or irritable skin" is intended to include intolerant and / or irritable skin which is physiological, that is to say that this intolerance or irritability is an intrinsic natural characteristic of these skins or that it is, for example, other terms, constitutional of these skins. By this expression, we will also target skin made intolerant and / or irritable due to chronobiological factors and / or seasonal factors or following dermatological procedures or cosmetic surgery or related. These gestures can be practiced by a chemical or physical technique. The best known are for example specific procedures such as pre and post peeling or laser, facelifts (ie any operations intended to correct the sagging of the skin), injections of fillers (otherwise called "fillers"), some plasty, liposuction and liposuction.

"Intolerant and / or irritable" scalps have a more univocal clinical symptom: sensations of itching and / or tingling and / or heating are mainly triggered by local factors such as rubbing, soap, surfactants, hard water to high concentration of limestone, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and / or food.

In the context of the present invention, the skins and / or the intolerant and / or irritable scalp considered do not exhibit an inflammatory character.

To this day, we still do not have a totally satisfactory solution to prevent and / or treat the dysaesthetic sensations of skins described as intolerant and / or irritable.

Unexpectedly, the inventors have found that pomegranate extracts can be effective, especially in children and adults, for the prevention or treatment of dysaesthesic sensations of skins and / or intolerant scalps and / or or irritable.

The Applicant has demonstrated that a pomegranate extract has an antagonistic activity of the release of a peptide derived from the calcitonin gene, the Calcitonin Gene Related Peptide or CGRP, which is one of the responsible for the appearance of dysaesthetic sensations.

Pomegranate (pomegranate) is the fruit of the pomegranate (Punica granatum), a shrub of the family Lythraceae.

This fruit, cultivated for several thousand years, has many merits, some of which have been known for a very long time. Its beneficial effects on hypertension have been described as well as its preventive effects of cancers of the prostate and breast or delaying the deterioration of cartilage which is responsible for osteoarthritis.

The patent application JP 09110710 describes the use of a pomegranate extract topically applied as an anti-inflammatory and antiallergic agent. The application US 2003/091665 aims to improve the appearance of the skin and in particular the reduction of wrinkles, sagging skin and pigmentation while the US Patent 6,800,292 aims at the treatment of dermatological disorders. Combinations of this extract with antioxidants are also known to prevent skin dehydration (JP 2002234814). However, none of these documents suggests a possible effect of this extract on dysaesthesic sensations.

Thus, the invention relates firstly to the cosmetic use of an effective amount of at least one pomegranate extract, as an agent for preventing and / or treating dysaesthetic sensations of skins and / or intolerant scalps and / or irritable. Thus, the extract according to the invention is of interest as a soothing agent.

By "effective amount" is meant in the sense of the present invention an amount sufficient to achieve the expected effect.

By "pomegranate extract" is meant as well fruit extracts, Punica granatum seed extracts and mixtures thereof in all proportions. Advantageously, using a fruit extract - or pomegranate extract - this extract can come from all parts of the pomegranate. The preferred pomegranate extract according to the present invention will be a whole fruit extract or even more preferably a whole fruit juice (often called "pomegranate fruit juice extract" by the suppliers).

The pomegranate extract can be obtained from any part of the pomegranate and in particular from the fruit including the seed.

By extract is meant both a crude mixture of parts of the plant roughly reduced in pieces and the extraction solvent that more or less elaborate fractions or preparations of the active principles solubilized during extraction. A total extract can be used, that is to say an extract comprising all parts of the pomegranate, from which the cellulosic (ligneous) parts have been removed. According to another embodiment of the invention, at least one extract enriched in certain fractions will be used.

The extract can be obtained by any method for preparing a plant extract known to those skilled in the art. In particular, the extract may be obtained by maceration of the part of the plant in water, or in a solvent composed of a mixture of water and an organic solvent, for example water-alcohol, or water- acetone, or water-propylene glycol, or water-butylene glycol. The plant / solvent ratio may vary for example and without limitation from 1/4 to 1/20.

Advantageously, the preparation of the extract begins by grinding the parts of the plant followed by maceration in the extraction solvent for several hours. Extraction can be performed with stirring to improve performance. The extraction can be carried out at ambient temperature or by increasing the temperature, for example at 50 ° C. or else at 60 ° C. Once extraction is complete, the solution is filtered.

The solution thus obtained can be concentrated by any method known to those skilled in the art. Similarly, the solution obtained can be lyophilized by any conventional freeze-drying method. A powder is thus obtained.

The extraction from the pomegranate fruit including the seed can result, according to a particular method of realization, in the preparation of an essential oil. The extract in the form of a concentrated solution, as well as the extract in powder form, as well as the extract in the form of an essential oil may be taken up in a suitable medium for oral consumption for humans.

According to an advantageous embodiment of the invention, the extract is chosen from aqueous extracts and alcoholic or hydro-alcoholic extracts of Punica granatum.

This extract may be introduced into a composition in the form of a freeze-dried powder, a liquid, an oil and / or if appropriate in a concentrated form. Such extracts are, for example, marketed by DRACO Natural Products under the trade names "Pomegranate Seed Oil" or "Pomegranate Powdered Extract, 40%" or by Naturex under the name "Pomegranate Fruit Juice Extract" or "Pomegranate extract 40%", or by 40 MMP Inc. under the trade name "Pomegranate Juice extract E40" or by the company Blue California under the trade name "Pomegranate Extract 700/0", or by the company Gui / Linen Natural Ingredients under the trade name "Pomegranate Seed PE" or registered for example with CAS number 84961-57-9.

It is understood that the choice of pomegranate extracts is made taking into account the purpose of the composition comprising them, that is to say intended for topical application to the skin or oral administration.

By the word "prevent" is meant to "reduce the risk of developing". By the term "treat", unless otherwise indicated, is meant any action to improve the comfort, well-being of an individual, this term therefore covers as well alleviate, relieve than cure.

In particular, the invention relates to the use of an effective amount of at least one pomegranate extract, as an agent for preventing and / or treating the dysaesthetic sensations of intolerant skin and / or scalp and / or irritable, these sensations being selected from tingling and / or tingling and / or itching and / or sensations of heating and / or skin discomfort and / or tightness of the skin and / or scalp.

These sensations can be caused by the application of a cosmetic product on the surface of the skin or scalp intolerant or irritable, by taking food, by exposure to sudden changes in temperature, by 25 exposure to atmospheric pollution and / or ultraviolet or infrared radiation. There are also associated factors like age and skin type.

The effective amount of the pomegranate extract will preferably be used at a content ranging from 0.0001 to 1000/0 by weight, especially 0.001 to 200/0 by weight or 0.01 to 150/0 by weight. , more particularly from 0.1 to 100/0 by weight, and even more preferably from 0.5 to 50/0 by weight relative to the total weight of the composition containing it.

The pomegranate extract content used for the topical route will preferably be from 0.001 to 200%, more preferably from 0.1 to 100% by weight, and still more preferably from 0.5 to 50% by weight relative to to the total weight of the composition containing it.

The pomegranate extract content used for the oral route will preferably be between 15 and 1000/0 by weight. In oral administration, the composition may therefore be constituted, in a particular embodiment of the invention, only pomegranate extract. However, this pomegranate extract content will be more preferably between 15 and 600/0 by weight and even more preferably between 15 and 300/0 by weight relative to the total weight of the composition containing it.

Another object of the present invention relates to a pomegranate extract for treating disorders associated with an excess of synthesis and / or release of CGRP and in particular the disorders mentioned above. The invention also relates to a pomegranate extract for its use in the treatment of disorders associated with an excess of synthesis and / or release of CGRP. These disorders will preferentially cutaneous disorders and in particular the disorders mentioned above.

The compositions according to the invention are generally administered topically, orally or parenterally. The preferred route of administration will be the oral route.

The topical way makes it possible to deploy all the properties of the assets at the level of a specific site, on the zones to be treated. We can use creams, lotions, ... But also local patches. The oral or parenteral route has the advantage of acting more globally on the entire skin and in these deep layers. For the parenteral route, systemic patch administration will be preferred.

The compositions according to the invention are food, nutritional, cosmetic or dermatological compositions. They will preferably be food compositions.

These compositions may be in any of the galenical forms normally used according to the route of use.

In the case of oral use, it favors the use of an unmanageable carrier. For ingestion, many embodiments of oral compositions and in particular dietary supplements are possible. Their formulation is carried out by the usual methods for producing dragees, capsules, gels, emulsions, tablets, capsules, spray or solutions. In particular, the active (s) according to the invention can be incorporated into all other forms of food supplements or fortified foods, for example food bars, or compacted powders or not. The powders can be diluted with water, in soda, dairy products or soy derivatives, or incorporated into food bars.

The active agents according to the invention may be formulated with the excipients and components customary for such oral compositions or food supplements, namely in particular fatty and / or aqueous components, humectants, thickeners, preservatives, texture agents, flavor and / or coating, antioxidants, preservatives and dyes customary in the field of food.

The formulating agents and excipients for oral composition, and especially for food supplements, are known in this field and are not the subject of a detailed description here.

In particular, the composition according to the invention may be a food composition for human consumption. This may include, in particular, whole nutritional foods, beverages, mineral waters, soups, dietary supplements and substitute foods, nutritional bars, confectionery, milk-based products or fermented milk, yogurt, milk-based powders, enteral nutrition products, children's and / or infants' compositions, cereal-based products or fermented cereal products, ice-cream, food products confectionery, chocolate, coffee, "culinary" products such as mayonnaise, tomato puree or salad dressings.

Particularly suitable as food or pharmaceutical carriers are milk, yoghurt, cheese, fermented milks, fermented milk products, ice creams, fermented cereal products, milk-based powders, formulas for children and infants, especially pet food, tablets, capsules or tablets, suspensions of liquid bacteria, oral supplements in dry form and oral supplements in liquid form.

For a topical application is meant an application on the skin in the broad sense, that is to say on any cutaneous surface of the body, whether or not it is covered with hair or hair, in particular mucosa, semi-mucosa , scalp. Such topical application allows topical treatment of irritable and / or intolerant skin, including irritable or intolerant lips and scalps, and signs that may be associated with them.

The dermocosmetic compositions, applicable topically, based on compounds according to the invention are preferably intended for the treatment of skin and mucous membranes and may be in the form of ointment, creams, milks, ointments, powders , soaked swabs, solutions, gels, sprays, lotions, or suspensions. They may also be in the form of microspheres or nanospheres or lipid or polymeric vesicles or polymeric patches and hydrogels allowing controlled release. These compositions topically can be in either anhydrous form or in aqueous form according to the dermocosmetic indication.

As regards the products intended to be applied topically in order to produce the desired effect in the context of the invention, they may be aqueous, hydroalcoholic or oily solutions, dispersions of the type of solutions or dispersions of the type lotion or serum, emulsions of liquid or semiliquid consistency of the milk type, suspensions or emulsions, cream type, aqueous or anhydrous gel, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic type and / or nonionic

The cosmetic and / or dermatological compositions, more particularly concerned by a topical application, may especially be in the form of aqueous, hydroalcoholic or oily solutions, dispersions of the type of solutions or dispersions of the lotion or serum type, of emulsions of liquid consistency. or semi-liquid of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (HIE) or vice versa (W / O), or suspensions or emulsions of soft, semi-solid or solid consistency of the cream type, aqueous or anhydrous gel, or microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and / or nonionic type. These compositions are prepared according to the usual methods.

These compositions may in particular constitute creams for cleaning, protection, treatment or care for the face, for the hands, for the feet, for large anatomical folds or for the body, (for example, day creams, night creams). , make-up removing creams, foundation creams, sunscreen creams), make-up products such as fluid foundations, make-up removing milks, protective or skincare body milks, after-sun milks, lotions, gels or skin care foams, such as cleaning or disinfecting lotions, sunscreen lotions, artificial tanning lotions, bathing compositions, deodorant compositions containing a bactericidal agent, aftershave gels or lotions , depilatory creams, or compositions against insect bites. The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars. They may also be used for hair in the form of aqueous, alcoholic or aqueous-alcoholic solutions, or in the form of creams, gels, emulsions, foams or in the form of aerosol compositions also containing a propellant under pressure. When the composition of the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetics and / or dermatological field. The emulsifier and the co-emulsifier may be present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition. .

When the composition of the invention is an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition.

In known manner, the cosmetic and / or dermatological composition of the invention may also contain adjuvants customary in the pharmaceutical and / or dermatological cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, fragrances, fillers, filters, bactericides, odor absorbers and dyes. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase and / or into the aqueous phase.

Fats which may be used in the invention include mineral oils such as, for example, hydrogenated polyisobutene and liquid petroleum jelly, vegetable oils such as, for example, a liquid fraction of shea butter, sunflower oil and almonds. apricot, animal oils such as perhydrosqualene, synthetic oils including Purcellin oil, isopropyl myristate and ethyl hexyl palmitate, and fluorinated oils such as perfluoropolyethers. It is also possible to use fatty alcohols, fatty acids such as stearic acid and, for example, waxes such as paraffin, carnauba and beeswax. It is also possible to use silicone compounds such as silicone oils and, for example, cyclomethicone and dimethicone, waxes, resins and silicone gums. These compounds can be functionalized or not.

As emulsifiers that may be used in the invention, mention may be made, for example, of glycerol stearate, polysorbate 60, the cetylstearyl alcohol / cetylstearyl alcohol mixture oxyethylenated with 33 moles of ethylene oxide sold under the name Sinnowax AOO by Henkel, the mixture of PEG-61PEG-32 / Glycol Stearate sold under the name of TefoseO 63 by Gattefosse, PPG-3 myristyl ether, silicone emulsifiers such as cetyldimethicone copolyol and sorbitan mono- or tristearate, PEG stearate -40, oxyethylenated sorbitan monostearate (200E).

As solvents that can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, and propylene glycol.

As hydrophilic gelling agents, mention may be made of carboxylic polymers such as carbomer, acrylic copolymers such as copolymers of acrylates / alkyl acrylates, polyacrylamides and in particular the polyacrylamide mixture, C13-14-Isoparaffin and Laureth-7 sold under the name Sepigel 3050 by the company SEPPIC, polysaccharides such as cellulose derivatives such as hydroxyalkylcelluloses and in particular hydroxypropylcellulose and hydroxyethylcellulose, natural gums such as guar, carob and xanthan and clays.

As lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, or else ethylcellulose and polyethylene.

Of course, the compositions according to the invention may contain several other active ingredients.

As active agents that can be used in combination with the pomegranate extract according to the invention, mention may be made of vitamins B3, B5, B6, B8, C or PP, retinol (vitamin A) and its derivatives, tocopherol ( vitamin E) and its derivatives, niacin, neuropeptide inhibitors, probiotics, prebiotics, NO-synthase inhibitors and ingredients that may cause irritation.

Specific examples of probiotic microorganisms are Bifidobacterium adolescentis, Bifidobacterium animes, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus (e.g. strain LC1, NCFB 1748); Lactobacillus amylovorus, Lactobacillus casei (eg Shirota strain), Lactobacillus rhamnosus (eg LGG strain), Lactobacillus brevis, Lactobacillus crispatus, Lactobacillus delbrueckii (subsp bulgaricus, lactis), Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus paracasei , Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus salivarius), Lactobacillus alimentarius, Lactobacillus curvatus, Lactobacillus casei subsp. casei, Lactobacillus sake, Lactococcus lactis, Enterococcus (faecalis, faecium), Lactococcus lactis (subsp lactis or cremoris), Leuconostoc mesenteroides subsp dextranicum, Streptococcus salivarius subsp. thermophilus, Streptococcus thermophilus, Saccharomyces cerevisiae, Saccharomyces boulardii, Propionibacterium freudenreichii, and mixtures thereof.

The probiotic will preferably be chosen from bacteria of the genera Bifidobacterium and / or Lactobacillus and in particular from bacteria of the species Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animes, Bifidobacterium lactis, Bifidobacterium infantis or Bifidobacterium adolescentis.

Preferentially, the probiotic will be Lactobacillus paracasei.

Particularly suitable bacteria are the strains of Lactobacillus johnsonii, Lactobacillus paracasei, Bifidobacterium adolescentis, Bifidobacterium longum and Bifidobacterum lactis NCC 2818 (also designated Bb12 or ATCC 27536) respectively deposited according to the Budapest Treaty to the National Collection of Cultures of Microorganisms (28 rue du Docteur Roux, F-75024 Paris cedex 15) 30/06/92, 12/01/99, 15/04/99, 15/04/99, 07/06/05 under the following designations CNCM 1-1225 , CNCM 1-2116, CNCM 1-2168 and CNCM 1-2170 and CNCM 1-3446, and the Bifidobacterium longum strain BB536. Bifidobacterium lactis strain CNCM 1-3446 can be obtained from Hansen (Hansen AIS Chr., 10-12 Boege AIIe, PO Box 407, DK-2970 Hoersholm, Denmark).

The microorganisms may be formulated as powders, i.e., in a dry form, or as suspensions or solutions.

More particularly, the prebiotics may be chosen from oligosaccharides, produced from glucose, galactose, xylose, maltose, sucrose, lactose, starch, xylan, hemicellulose, inulin, gums, of the acacia type, for example, or one of their mixtures. More particularly, the oligosaccharide comprises at least one fructooligosaccharide. More particularly, this prebiotic may comprise a mixture of fructooligosaccharide and inulin.

According to another of its objects, the invention relates to a composition, preferably useful according to what is defined above, comprising, in a physiologically acceptable medium, at least one pomegranate extract present at a rate of 0.0001% to 30% by weight relative to the total weight of the composition, in combination with at least one neuropeptide inhibitor, in particular a neuropeptide Y antagonist, a substance P antagonist, a CGRP antagonist and / or a probiotic and / or a prebiotic and / or a NO-synthase inhibitor and / or an ingredient capable of causing irritation. Obviously, the neuropeptide inhibitor mentioned above will therefore be a different active ingredient than pomegranate extract.

According to the invention, a "physiologically acceptable medium" is a cosmetically or pharmaceutically acceptable medium compatible with the skin, the mucous membranes, the nails and / or the hair.

By "cosmetically acceptable medium" means a medium without unpleasant appearance, and which does not generate tingling, tightness or redness unacceptable to the user.

Examples of NO-synthase inhibitors suitable for use in the present invention include in particular a plant extract of the Vitis vinifera species which is in particular marketed by Euromed under the name Leucocyanidines of extra grapes, or by Indena under the name Leucoselece, or finally by Hansen under the name Extract of marc of grapes; a plant extract of the species Olea europaea which is preferably obtained from olive leaves and is especially marketed by VINYALS in the form of dry extract, or by Biologia & Technologia under the trade name Eurol BT®; and an extract of a plant of the species Gingko biloba which is preferably a dry aqueous extract of this plant sold by Beaufour under the trade name "Ginkgo biloba extract standard".

The composition according to the invention comprising a NO-synthase inhibitor as defined above can advantageously be used to prevent or treat skins and / or intolerant and / or irritable scalps.

Among the compounds likely to cause skin irritation, mention may in particular be made of cosmetic compounds or active agents, dermatological compounds or active agents, surfactants, in particular anionic surfactants, preservatives, detergents, perfumes, and in particular alcoholic perfuming solutions, solvents, and the like. , propellants and mixtures thereof.

More particularly, as dermatological or cosmetic active agents, mention may be made of certain desquamating agents which may also be peeling agents.

The term "peeling" is the French word "peel" which means "peel". A peeling thus classically denotes a controlled action of irritation of the surface of the skin by a chemical substance or by a physical process.

A peel-like operation may for example consist in applying a chemical substance to the skin in order to cause limited and controlled destruction of the epidermis and the superficial layers of the dermis, in order to improve certain disorders of the cutaneous appearance.

Among the agents specifically for peeling, mention may be made of abrasive / exfoliating particles of mineral, organic, natural or synthetic sources. Mention may be made more particularly of particles of pumice stone, silica, polyethylene balls, nylon and powders of fruit cores. Among these desquamating agents, the following compounds are capable of causing irritation of the skin: saturated monocarboxylic acids (acetic acid) and unsaturated acids, saturated and unsaturated dicarboxylic acids, saturated and unsaturated tricarboxylic acids; α-hydroxy acids and R-hydroxy acids of monocarboxylic acids; the α-hydroxy acids and R-hydroxy acids of the dicarboxylic acids; α-hydroxy acids and R-hydroxy acids, tricarboxylic acids, ketoacids, α-ketoacids, R-ketoacids of polycarboxylic acids, polyhydroxy monocarboxylic acids, polyhydroxybicarboxylic acids and polyhydroxy tricarboxylic acids.

Among desquamating agents, those capable of acting on the enzymes involved in the desquamation or degradation of corneodesmosomes may also be capable of causing skin irritation.

Among these, there may be mentioned the chelating agents of inorganic salts such as aminosulphonic compounds and in particular (N-2-hydroxyethylpiperazine-N-2-ethane) sulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid derivatives (procysteine); glycine-type alpha amino acid derivatives (as described in EP 0 852 949, as well as sodium methyl glycine diacetate marketed by BASF under the trade name TRILON M®); honey ; sugar derivatives such as O-octanoyl-6-D-maltose, 0-Iinoleyl-6-D-glucose and N-acetyl glucosamine.

Retinoids are also compounds that can cause skin irritation. For example, retinol and its esters, retinal, retinoic acid and its derivatives, such as those described in documents FR 2 570 377, EP 0 199 636, EP 0325 540, EP 0 402 072, may be mentioned among them, and adapalene.

Salts and derivatives, such as cis or trans forms, racemic mixtures, dextrorotatory or levogenic forms of the compounds mentioned above are also considered as compounds capable of causing irritation of the skin.

As surfactants, mention may be made of anionic, cationic and amphoteric surfactants, more particularly anionic surfactants such as alkyl sulphates and alkyl ether sulphates, for instance lauryl sulphate and lauryl ether sulphate, and their salts, especially sodium salts.

According to a preferred embodiment of the invention, the compound likely to cause irritation of the skin is chosen from retinoids, ahydroxyacids, R-hydroxy acids, saturated and unsaturated dicarboxylic acids such as octadecene dioic acid or Arlatone DIOC DCA sold by Uniqema, anionic, cationic or amphoteric surfactants, n-octanoyl 5-salicylic acid, antiperspirant active agents such as aluminum salts, (N-2-hydroxyethylpiperazine-N-2- acid) ethane) sulfonic acid (HEPES) and cinnamic acid.

The compound capable of causing skin irritation may be present in the composition according to the present invention in an amount sufficient to cause a skin irritation reaction. By way of example, it may be present in a content ranging from 0.0001% to 700% by weight, preferably from 0.01% to 500% by weight and better still from 0.1% to 300% by weight. relative to the total weight of the composition.

According to another of its objects, the present invention relates to a cosmetic process for treating dysaesthesic sensations of intolerant and / or irritable skins and / or mucous and / or semi-mucous membranes and / or scalp, comprising at least one step of topical application to the skin and / or the scalp and / or oral administration of an effective amount of at least one pomegranate extract or a composition as defined above, according to the technique of usual use of these compositions.

For example: the topical application can be made by spreading on an area of the body, or even by massage to penetrate, creams, gels, serums, lotions, cleansing milks or after-sun compositions on the skin or on dry hair, application of a hair lotion on wet hair, shampoos, or application of toothpaste on the gums.

The method according to the invention may comprise a single application or a single administration. According to a particular embodiment, the administration or the application is repeated for example 2 to 3 times daily over a day or more and generally over an extended period of at least 4 weeks, or even 4 to 15 weeks, with the case one or more periods of interruption.

This process is advantageously carried out before and / or after a mechanical or chemical peeling step, or exfoliation of the skin. Indeed, by its soothing properties, the pomegranate extract according to the invention prevents, relieves or treats any discomfort reaction such as dysaesthesic sensations. In the case where the pomegranate extract is administered orally, the daily doses of pomegranate extract are preferably between 0.5 and 2500 mg / day, more precisely between 5 and 500 mg / day.

In the following description and examples, unless otherwise indicated, percentages are percentages by weight and ranges of values in the form "between ... and ..." include the specified lower and upper bounds. The ingredients are mixed, before they are shaped, in the order and under conditions easily determined by those skilled in the art. The following examples are presented by way of illustration and not limitation of the scope of the invention.

EXAMPLES

Example 1: Composition Examples 1.1. Unidose gel composition20 Active ingredient% weight Pomegranate extract: Whole fruit juice 1 (Naturex) 1010 cfu Lactobacillus johnsonii Excipient Sugar syrup 50 Maltodextrin 17 Xanthan gum 0.8 Sodium benzoate 0.2 Water gsp100 You can take a dose of 200 to 400 ml a day. 1.2. Capsule composition mg / capsule Pomegranate extract: Whole fruit extract 1010cfu (Draco) 5 Lactobacillus paracasei Glycerin 150 Magnesium stearate 0.02 Natural flavor One to three of these capsules per day can be taken. 1.3. Capsule composition

In the formulation of Example 2 is added a vitamin complex comprising 60 mg of vitamin C, 100 μg of vitamin E and 6 mg of β-carotene.

1.4. Capsule Composition The formulation of Example 2 is supplemented with a vitamin complex comprising 100 mg vitamin C, 100 μg vitamin E and 6 mg lycopene per capsule.

1.5. Composition of body lotion in the form of spray (% by weight) Pomegranate extract: Whole fruit juice (Naturex) 5.00 Vitamin E 0.05 10 20 Isopropanol 40.00 Preservative 0.35 Water qs 100.00 1.6 . Composition of face cream (% by weight) Pomegranate extract: Whole fruit extract 5.00 (Draco) Vitamin E 0.05 Isopropanol 40.00 Glycerol stearate 1.00 Cetyl stearyl alcohol / alcohol 3.00 cetylstearyl oxyethylenated 33 mole EO (Sinnowax AO sold by Henkel) Cetyl alcohol 1,00 Dimethicone (DC 200 Fluid sold by the Dow Corning company) Vaseline oil 6,00 Isopropyl myristate (Estol IPM 1514 3,00 sold by Uniquema) Glycerin 20.00 Preservative 0.30 Water qs 100.00 1.7. Gel composition for facial care 0/0 by weight Pomegranate extract: Whole fruit juice 3.00 (Naturex) Vitamin E 0.05 Vitamin C 2.50 Isopropanol 40.00 Preservative 0.30 Water qs 100.00 Example 2 - Demonstration of the activity of the pomegranate extract according to the invention The effects of the pomegranate extract provided by the company Naturex (Avignon, France) on the amount of "Calcitonin Gene-Related Peptide" (CGRP) released by sensory neurons (NS) maintained in culture after stimulation with capsaicin (10-6 M) were studied.

The effects of this extract were evaluated by ELISA measuring the release of CGRP by NS.

Materials and method 10 - Biological model Cell type: Sensory neurons (NS) Culture conditions: 37 ° C, 5% CO2 Culture medium: DMEM / HAM F12 supplemented with Glutamine 2 mM Penicillin 50 U / ml Streptomycin 50 μg / ml Nerve growth factor (NGF) 20 ng / ml Neurotrophin 3 (NT3) 5 ng / ml Supplement N2 1 Test medium: DMEM / HAM F12 - Compounds tested, reference and stimulation factor Compound tested Appearance / Solution Dilution Concentrations Storage stock tested Extract Powder 100 mg / mi Trial medium From 8x10-3 mg / ml pomegranate: Storage juice in DMSO 6.25x10.5 mg / mi whole fruit at + 4 ° C with a factor of (Naturex, the dilution shelter 2 Avignon, France) light Reference Stock Solution Dilution Tested Concentration Capsazepine 10-2 M ethanol Test Medium 10-5 M 15 Stock Solution Factor Dilution Concentration Stimulation Tested Capsaicin 10-2 M Ethanol Medium test 10-6 M - Culture and processing

Sensory neurons (NS) were cultured in 96-well plates for 8 days.

The cells were then pre-incubated or not (control) for 30 minutes with the compounds under test. After preincubation, the cells were incubated for 20 minutes in test medium containing the stimulation factor (capsaicin at 10-6 M) and containing or not (control) the compounds under test, the reference (capsazepine 10-5 M) or solvent control (DMSO at 0.2%, 0.02% and 0.008%). An uninduced control was also performed in parallel. All the treatments were performed in n = 6.

After incubation, the culture supernatants were collected and stored in order to assay the amount of secreted CGRP. In addition, a viability test was performed on the cell mats according to a standard MTT reduction protocol.

- Quantification of CGRP by ELISA

The amount of CGRP was evaluated in the culture supernatants using an ELISA kit and according to the supplier's specifications. ELISA kit Reference Limit of detection limit lower detection superior CGRP SPI bio, 15.6 pg / ml 500 pg / ml ref. A05482 The results are expressed in pg / ml of CGRP and in percentage of the release compared to the control series. - Evaluation of cell viability

Transformation of the colorless tetrazolium salt (MTT: 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) into blue formazan crystals, soluble in DMSO, is proportional to activity of succinate dehydrogenase (a mitochondrial enzyme). As a result, transformation of MTT into formazan crystals by succinate dehydrogenase is proportional to the number of living cells. The cells were incubated in the presence of MTT and then dissociated and the formazan crystals solubilized. The optical density (OD) at 540 nm, representative of the number of living cells, was measured on a plate reader (SoftMax, Molecular Devices).

- Data processing

The raw data has been transferred and processed under Microsoft Excel® software.

Intergroup comparisons were performed using the Student's T-test. Statistical analyzes can be interpreted if n> _5. However for n <5, the calculated data are provided for information only.

The percentage inhibition is calculated according to the following formula: Stimulated Control Mean - Inhibition Value (%) = X 100 Stimulated Control Mean - Mean Basal Control The standard error of the mean (esm) represents the deviation from the mean of the sample against the average of the true population. The esm is calculated by dividing the Sd by the square root of the sample size.

The percentage of viability is obtained according to the following formula = (compound DO DO) x 100-

25 RESULTS

The results showing the effect of a pomegranate extract on capsaicin-induced release of CGRP after 30 minutes of preincubation of the compound and 20 minutes of incubation in the presence of capsaicin are presented in the appendix as a table (FIG. 1).

Stimulation of sensory neurons (NS) by capsaicin (10-6 M) markedly increased CGRP release. This effect was strongly inhibited by treatment with capsazepine (10-5 M). These results were expected and validate the test.

DMSO, tested between 0.0080 / 0 and 0.20 / 0 and used for the preparation of the compounds under test, did not modify the release of capsaicin CGRP-induced sensory neurons. In addition, no cytotoxic effect was observed following this treatment. Pomegranate extract, tested between 2.5 x 10-4 and 8 x 10-3 mg / ml, significantly and significantly inhibited capsaicin-induced CGRP release. This inhibitory effect was observed without the cytotoxic effect of the compound. At lower concentration, this effect was no longer visible.

CONCLUSION

In conclusion, pomegranate extract markedly inhibited the release of CGRP by capsaicin-stimulated sensory neurons. This extract, by virtue of its inhibition of the release of CGRP by cutaneous sensory neurons, therefore has an effect on the appearance of dysaesthetic sensations.

Claims (10)

REVENDICATIONS1. Non-therapeutic cosmetic use of an effective amount of at least one pomegranate extract, as an agent for preventing and / or treating the dysaesthetic sensations of skins and / or intolerant and / or irritable scalp. 2. Use according to claim 1, for treating sensations selected from tingling and / or tingling and / or itching and / or sensations of heating and / or skin discomfort and / or tightness of the skin and / or scalp. 3. Use according to any one of the preceding claims, characterized in that the extract is present in a composition in a proportion of 0.0001 to 100% by weight relative to the total weight of said composition. 4. Use according to any one of the preceding claims, characterized in that the pomegranate extract is an extract of whole fruit. 20 5. Use according to any one of the preceding claims, characterized in that said extract is associated with at least one compound selected from vitamins B3, B5, B6, B8, C or PP, retinol and its derivatives, tocopherol and derivatives, niacin, neuropeptide inhibitors, probiotics, prebiotics, NO-synthase inhibitors and ingredients which may cause irritation. 6. Use according to any one of the preceding claims, characterized in that said extract is associated with a probiotic selected from bacteria of the genera Bifidobacterium and / or Lactobacillus. 7. Use according to the preceding claim, characterized in that said probiotic is chosen from bacteria of the species Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis or Bifidobacterium adolescentis and mixtures thereof. 8. Composition, useful according to any one of claims 3 to 7, 40 comprising, in a physiologically acceptable medium, at least one pomegranate extract present in a proportion of 0.0001% to 30% by weight relative to the poidstotal of the composition, in combination with at least one neuropeptide inhibitor selected from a neuropeptide Y antagonist, a substance P antagonist and a CGRP antagonist and / or a probiotic and / or a prebiotic and / or a NO-synthase inhibitor selected from a plant extract of the species Vitis vinifera, a plant extract of the species Olea europaea and an extract of a plant of the species Gingko biloba and / or an ingredient likely to cause irritation selected from a desquamating agent, surfactants, preservatives, detergents, perfumes, solvents, propellants and mixtures thereof. 9. Composition according to Claim 8, characterized in that it is in the form of aqueous solutions, hydroalcoholic or oily, dispersions of the type solutions or dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency. of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (HIE) or vice versa (W / O), or suspensions or emulsions of soft, semi-solid or solid consistency of the cream type, of aqueous or anhydrous gel or microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and / or nonionic type. 10. Non-therapeutic cosmetic method for treating dysaesthetic sensations of skins and / or intolerant and / or irritable scalps comprising at least one stage of topical application to the skin and / or the scalp and / or oral administration an effective amount of at least one pomegranate extract or a composition comprising a pomegranate extract.