Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9789—Magnoliopsida [dicotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
  • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/16—Emollients or protectives, e.g. against radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/005—Preparations for sensitive skin

Definitions

• the present invention relates to the field of cosmetology and dermatology, more particularly skincare and mucosal skincare cosmetics, in particular skins and / or mucous membranes which are sensitive, sensitized, reactive, fragile, and / or weakened, and use of a protein extract of ungerminated seed deoiled from Moringa.
• the genus Moringa comprises some 14 species of plants (including Moringa peregrina, M. aptera, M. concanensis, M. clroithardii, M. hildebrandtii, M. longituba), of which Moringa pterygosperma (synonym Moringa oleifera) is the best known.
• the different parts of the tree (leaves, roots, bark of roots, flowers, seeds) are used in traditional medicine in the countries where it grows.
• the seeds of Moringa are characterized by the presence of an oil whose content varies between 21 and 53% according to the species and the maturity of the seeds.
• the levels mentioned in the literature range from 21 to 34%.
• Moringa oil also called Behen or Ben oil
• This oil has been used by formulators in cosmetics until the last century and its use has been "rediscovered” recently.
• Moringa seeds have more recently attracted the attention of researchers for their protein extract.
• the application EP1064008 describes the use of a protein extract of Moringa seeds on the skin and the mucous membranes for their softening effect, physiological conditioner, moisturizing, restructuring, repairing, anti-wrinkle and as an antipollution agent.
• Such an extract is in particular marketed by BASF under the name Purisoft® for its purifying and anti-pollution effect.
• the application WO02 / 096448 describes for its part the use of a protein seed extract delipidated or not in the fields of deodorization, elimination of bad odors, cleanliness, personal hygiene, oral hygiene, dental care.
• this document further describes that such an extract has a soothing, softening, moisturizing and reducing the feeling of tiredness.
• this soothing effect is at no time suggested as being related to a decrease in the reactivity of the skin or to a treatment of inflammation of the skin and / or mucous membranes.
• this document indicates that the extract maintains the balance of the bacterial and fungal flora on the surface of the mucous membranes, but only in the sense that it does not, unlike the other conventional deodorants.
• the extract may be used in the treatment of sensitive and sensitized, reactive, fragile, weakened and / or intolerant skins and / or mucous membranes, in particular by reducing inflammation, or that he may have a beneficial effect on the beneficial commensal flora of the skin and / or mucous membranes, by preserving and / or increasing it.
• Application FR2946879 also describes a Moringa extract for its use in cosmetics. However, it is an entire seed extract, that is to say, not deoiled.
• the application CN103223010 also describes the use of a seed extract of Moringa seeds in cosmetics, in particular obtained by extraction with a supercritical fluid, extraction process which extracts the oily compounds.
• the present invention thus relates to a new use of a protein extract of non-germinated seed de-oiled Moringa oleifera that has never been described or suggested in the prior art.
• Increased neuro-sensory activity which is characterized by changes in the nerve endings of the epidermis, neurotransmitter accumulation, or disruption of information transmission in the central nervous system, is also a factor the sensitivity of the skin.
• a third additional cause of skin sensitivity is an increased immune sensitivity comprising in particular a measurable increase in the density of epidermal Langerhans (CL) cells, which can, in the most extreme cases, lead to pathologies such as urticaria. contact, irritative or allergic contact dermatitis, or atopic dermatitis.
• the polymorphism of sensitive skin is reflected by subjective sensations such as redness, feeling of warmth or warmth, tension, tingling, tingling, tightness. These unsightly and / or uncomfortable manifestations are characteristic of sensitive skin. In the most extreme cases, irritations or allergic reactions are also described.
• the non-germinated seed extract of Moringa oleifera dewaxed seed also has an impact on the cutaneous and / or mucosal microbial flora, in particular by activating the growth of commensal beneficial strains, particularly those making it possible to fight against inflammation, such as S. epidermidis and / or A. Iwoljfii (Example 3b), but also by inhibiting the growth of opportunistic pathogenic strains such as Propionibacterium acnes (Example 3a).
• the skin is indeed a complex ecosystem on which proliferate several types of microorganisms such as bacteria and fungi. These microorganisms constitute the cutaneous flora, also called cutaneous microbial flora. We distinguish between: - the commensal beneficial resident flora consisting of microorganisms proliferating conventionally on healthy skin, permanently by drawing their nutrients from the skin, and bringing known benefits to the skin,
• transient flora present on the skin under abnormal conditions, for example by contact with soiled elements, and which can become pathogenic in the event of proliferation.
• strain Staphylococcus epidermidis and the strain Acinetobacter Iwoljfii. These strains are found especially in the face on healthy skins where they participate in maintaining the balance of commensal skin flora.
• the strain Staphylococcus aareus may be considered part of the transient skin flora potentially pathogenic to human skin and the strain Propionibacterium acnes as part of the resident opportunistic pathogenic flora.
• Staphylococcus aureus and Propionibacterium acnes in case of proliferation can indeed cause a microbial imbalance in the skin flora, making it more vulnerable to infections and fungi, induce inflammation, including redness, swelling or even pimples and a burning sensation and / or localized heat accompanied by pain, pigmentation spots or scars for example following acne and therefore an inhomogeneity of the complexion, and finally may be the cause of actual infectious skin diseases such as skin infections such as boils, folliculitis, ulcers, abscesses, sycosis impetigo, ecthyma, erysipelas or acne.
• a disturbance of the commensal flora can also be at the origin of mycoses of the skin such as candidiasis.
• a disturbance of the flora of the oral mucosa, in particular of the gingival mucosa, can be the cause of gingivitis.
• Cosmetic or dermatological solutions are already known to act on the cutaneous microbial flora. On the other hand, their actions are often antiseptic. These modes of action are thus not targeted because they are not directed against a strain of specific microorganism.
• There are solutions for acting on the cutaneous microbial flora by targeting a group such as bacteria in the field of pharmaceutical ingredients. Examples include antibiotics.
• antibiotics have the disadvantage of not always being tolerated especially in oral administration and further induce the development of resistance.
• antibiotics in general act not only on the pathogenic microbial flora, but also on the commensal microbial flora, which can result in the appearance of fungal infections. Therefore, there is a significant need in the field of cosmetic and dermatology to provide active ingredients on the cutaneous microbial flora, especially by targeted action on a particular microbial strain or by protection of commensal flora, which are readily available and do not have the disadvantages or side effects described above.
• the present invention therefore relates to the cosmetic use of a protein extract of non-germinated seed deoiled Moringa oleifera, preferably a protein extract ungerminated seed delipidated, in particular a protein extract of deoiled cake, more particularly delipidated, non-germinated seeds, more advantageously non-germinated seed almonds, Moringa oleifera, for the treatment of skin and / or sensitive mucosa, sensitized, fragile and / or fragile.
• a protein extract of non-germinated seed deoiled Moringa oleifera preferably a protein extract ungerminated seed delipidated, in particular a protein extract of deoiled cake, more particularly delipidated, non-germinated seeds, more advantageously non-germinated seed almonds, Moringa oleifera, for the treatment of skin and / or sensitive mucosa, sensitized, fragile and / or fragile.
• sensitive skins and / or mucous membranes may be defined as skins which, by nature, tolerate only very little aggressive agents, especially environmental agents such as pollutants, climatic factors (wind , cold, heat), UV exposures, emotional factors including stress and / or chemical agents (heavy metals, detergents, compounds contained in cosmetic treatments such as perfumes, preservatives, alcohols, pH, AHA or dermatological such as vitamin A acid) and / or aggressive conditions including sweating and mechanical aggression such as waxing, shaving, rubbing and even water especially limestone.
• Sensitive skins are not skins with pathological characters unlike allergic skins.
• the "sensitive skin” character can be esteemed by the subject himself with subjective skin sensations or by the dermatologist with objective cutaneous reactions.
• Unsightly and uncomfortable manifestations can be generalized to the whole body, but most of the time they can have well-defined localizations such as, for example, the scalp, the face, the skin folds, the buttocks in the infant, etc. It can therefore be areas of skin and / or sensitive mucosa.
• the sensitized skin is skins made momentarily sensitive so not pathological as such.
• Reactive skin, or hyperreactive or intolerant or irritable skin is a skin whose threshold of tolerance has decreased and which reacts excessively.
• Fragile or fragile skin that is to say, temporarily fragile, is a skin whose barrier function is weakened.
• This condition may be related to the condition of the individual, the elderly and infants with fragile skin for example. This condition can result from chemical or physical aggression (abrasion, friction, cuts).
• the term "cosmetic" is intended to mean a non-pharmaceutical, non-therapeutic use which is not intended for the prevention and / or treatment of skins and / or mucous membranes qualified as pathological by a specialist in the field, such as as a dermatologist. It is therefore a use on healthy skin and / or mucous membranes.
• Skin and / or healthy mucosa means all or part of an area of skin including the scalp and / or healthy mucosa, especially human, thus having no infection, scar, disease or affection dermal candidiasis, impetigo, psoriasis, eczema, acne, ichthyosis, gingivitis or dermatitis or sores or wounds or ulcers or ulceration or burning and / or other dermatoses, or aphtosis or inflammation or irritation.
• the term "skin” means the skin of all or part of the body, in particular human, selected from the legs, feet, armpits, hands, thighs, belly, Vietnameselleté, neck, the arms, the torso, the back, the labial mucous membrane, the face and / or the scalp, advantageously the cleavage and / or the face, still advantageously the face.
• the term "mucosa (s)" the ocular mucosa, the vaginal mucosa, the urogenital mucosa and / or the oral mucosa, especially the oral labial mucosa and / or the gingival mucosa, preferentially , ocular and / or oral mucosa, and more preferably, the gingival mucosa, labial and / or ocular, more preferably the gingival mucosa.
• the term "treatment of skin and / or sensitive, sensitized, fragile and / or weakened skins and / or mucous membranes” means reducing their reactivity so as to render them less sensitive and / or fragile, for example by decreasing and / or inhibiting the release of IL6 and / or IL8 cytokines with respect to sensitive, sensitized, fragile and / or fragile skin and / or mucosa not treated with the extract according to the invention, in particular as described in US Pat. example 2.
• the ungerminated seed protein extract deoiled from Moringa oleifera according to the invention is topically and / or orally acceptable.
• topically acceptable means an ingredient suitable for topical application, non-toxic, non-irritating to the skin and / or the mucous membranes, which does not induce an allergic response and which does not induce an allergic response. is not chemically unstable.
• orally acceptable means an ingredient suitable for oral administration, non-toxic, which induces no allergic response and which is not chemically unstable.
• the use of the extract according to the invention is to prevent and / or treat the unsightly and / or unpleasant and / or uncomfortable manifestations of sensitive and sensitized skins and / or mucous membranes, which are fragile and / or weakened, advantageously chosen from redness, feeling of warmth or warmth, tension, tingling, tingling, tugging, and a mixture of these manifestations. It brings a feeling of comfort to the skin and / or mucous membranes.
• the present invention furthermore relates to the cosmetic use of a protein extract of non-germinated seed de-oiled with Moringa oleifera, advantageously of a protein extract of non-germinated delipidated seed, in particular of a protein extract of deoiled cake, more particularly delipidated non-germinated seeds, more advantageously ungerminated seeds almonds, Moringa oleifera, for the increase and / or protection and / or maintenance of the commensal beneficial flora in the skin and / or mucous membranes, in particular commensal beneficial bacterial flora, particularly selected from the group consisting of Staphylococcus epidermidis, Acinetobacter Iwolffii and mixtures thereof.
• the term "commensal strain” means a strain or flora beneficial to the skin and / or the mucous membranes, which does not or does not become pathogenic for the skin and / or the mucous membranes.
• commensal microorganisms selected from the group consisting of fungi, yeasts and bacteria, preferably bacteria, present or made on the skin or the mucous membranes, in particular human and whose action is beneficial for the skin and / or the mucous membranes such as Staphylococcus hominis, S. warneri, S. capitis, S epidermidis, Acinetobacter Iwolffii, preferentially Staphylococcus epidermidis and / or Acinetobacter Iwolffii.
• the term "increase the commensal flora beneficial to the skin and / or mucous membranes” increase the growth of commensal flora beneficial to the skin and / or mucous membranes.
• Several methods can be used to measure the content of strains of microorganisms in the skin and / or mucous membranes, including a count of colonies present on the skin or mucous membranes, an in vitro optical density measurement after recovery of samples containing the strains or a PCR measurement.
• the content of the microorganisms is measured in vitro by optical density after recovery of samples containing the strains as exemplified in Example 3b.
• the use of the ungerminated seed protein extract deoiled from Moringa oleifera according to the invention is not to improve the barrier function of the skin or to increase the hydration of the skin and / or mucous membranes neither for the treatment of dry skin, nor to soothe the skin and / or the mucous membranes, in particular the skin and / or the dry mucous membranes, nor to soften and / or reduce the sensation of fatigue of the skin and / or mucous membranes .
• the use of the non-germinated seed extract of Moringa oleifera dehydrated seed according to the invention is not to protect the skin and / or the mucous membranes against pollution, more particularly urban pollution (such as heavy metals). , the exhaust gases and / or cigarette smoke) and advantageously against the damage caused by the pollution, and / or to purify the skin and / or the mucous membranes by eliminating the particles that make the skin and / or the impure mucous membranes such as pollution particles (eg coal particles).
• pollution particles eg coal particles
• the cosmetic use according to the invention is to prevent and / or reduce and / or eliminate the unsightly and / or uncomfortable effects of skins and / or mucous membranes whose commensal beneficial flora is impaired, in particular to prevent and / or reduce and / or delay the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular for preventing and / or reducing and / or delaying the formation of black spots and / or comedogenesis and / or the shiny appearance of the skin, and / or maintain and / or improve the homogeneity of the complexion of the skin and / or mucous membranes, for example by suppressing and / or reducing redness and / or irregularities, and / or to prevent and / or treat the sensation of heat and / or heat of the skin and / or mucous membranes and / or to prevent and / or reduce hair loss and / or hair loss, and
• the homogeneity of the complexion of the skin can for example be measured by chromametry or by image analysis.
• the latter method of measurement in vivo consists of taking high resolution photographs in cross polarized configuration of the face of volunteers taken at 45 ° before and after application of the tested product.
• an image analysis makes it possible to extract and to quantify specific parameters (for example: L *, a *, b *, C, h °) related to the color, the brightness, the homogeneity, and the texture of the skin.
• the beneficial commensal flora is a microorganism selected from the group consisting of Staphylococcus epidermidis, Acinetobacter Iwolffii and mixtures thereof.
• the non-germinated seed extract of dewaxed Moringa oleifera is applied topically, advantageously on specific parts and / or areas of the body selected from the legs, feet, armpits, hands , neck, Vietnameselleté, belly, arms, thighs, hips, buttocks, waist, crotch, groin, torso, back, labial mucous membrane, face and / or leather and / or the oral and / or gingival mucosa, especially shaved areas, areas of maceration such as infant seat, areas of plaice such as the armpits, the back of the elbows, the back of the knees, the buttocks, crotch, groin, neck, and / or around the lips and / or excessively cleaned areas.
• the term “topical route” means the application of the ungerminated seed extract of Moringa oleifera and / or of the composition and / or of the ingredient according to the invention to the surface of the skin and / or mucous membranes, in particular by direct application or by spraying.
• the ungerminated seed extract of Moringa oleifera is orally administered, in particular for the purpose of treating the gingival mucosa.
• the cosmetic comprising it is in the form of a cosmetic composition intended for oral administration, in particular on the gingival mucosa, further comprising a suitable cosmetic vehicle.
• cosmetic and / or pharmaceutical ingredient (s) means one or more plant extracts and / or one or more natural or synthetic molecules and / or their mixtures intended for a particular purpose.
• Cosmetic ingredients are defined in particular by the International Nomenclature of Cosmetic Ingredients (INCI).
• suitable cosmetic or pharmaceutical vehicle means that the composition or the components thereof are suitable for use in contact with the skin and / or the human mucosa without toxicity, incompatibility, instability, allergic response, or their equivalents, undue.
• the extract according to the invention may be obtained by various extraction methods known to those skilled in the art, advantageously chosen from maceration, with or without stirring, hot decoction, grinding, ultrasonic grinding or ultrasonic grinding. using a mixer.
• the extraction is carried out by maceration, advantageously still with stirring.
• the extraction may be carried out at a temperature of 4 ° C. to 300 ° C., preferably from 20 ° C. to 80 ° C., it being understood that 20 ° C. corresponds to the ambient temperature, advantageously between 20 and 25 ° C.
• the extraction will be conducted for a period of 30 minutes to 12 hours, preferably for a period of 1 hour to 5 hours, more preferably for a period of 1 hour to 2 hours. Very advantageously, the extraction will be conducted for a period of 1 hour.
• the extract according to the invention may be obtained by extraction in a protic polar solvent, advantageously chosen from the group consisting of water, an alcohol, a glycol, a polyol, a water / alcohol mixture, from 99/1 to 1/99 (w / w), a water / glycol mixture of 99/1 to 1/99 (w / w) and a water / polyol mixture of 99/1 to 1/99 (w / w) (such as water mixed with ethanol, glycerol and / or butylene glycol and / or other glycols such as xylitol and / or propanediol, etc.), advantageously in the water as the sole solvent.
• a protic polar solvent advantageously chosen from the group consisting of water, an alcohol, a glycol, a polyol, a water / alcohol mixture, from 99/1 to 1/99 (w / w), a water / glycol mixture of 99/1 to 1/99 (w / w) and
• extract obtained by aqueous extraction means any extract obtained by extraction with an aqueous solution containing more than 60% by weight, advantageously at least 70% by weight, in particular at least 80% by weight. , more particularly at least 90% by weight, particularly at least 95% by weight, of water relative to the total weight of the aqueous solution, more advantageously not containing glycol and in particular not containing any alcohol, more particularly containing only water.
• the extract can be obtained from an amount of 0.1% to 20% of fresh or dry material, preferably dry, preferably from 1% to 10%, more preferably from 5% to 10%, very advantageously from in a quantity of 10% by weight of dry matter, non-germinated seeds delipidated from the plant Moringa oleifera, relative to the total weight of the non-germinated seeds delipidated plant and solvent.
• non-germinated seed protein extract de-oiled from Moringa oleifera is as described in patent EP1064008 and is marketed by BASF under the trade name Purisoft®.
• a polar protic solvent in particular chosen from alcohols, polyols, glycols, water and their mixture in any proportion, advantageously with a aqueous solvent, that is to say based on water, even more advantageously with water as sole solvent, so as to obtain a crude extract, preferably as described in Example la.
• the extraction is carried out at room temperature.
• the aqueous solvent may be a salt solution at different pH or a buffered medium, more preferably at a pH of between 4 and 8.
• the method may also comprise an additional step c) after step b) of precipitating the crude extract, not modifying the pH of the aqueous crude extract obtained in step b) so as to obtain a basic pH, in particular greater than 8, more preferably greater than 11, for example with the aid of NaOH, and recovery of the precipitate obtained, advantageously as described in Example 1b.
• the precipitate can then be washed and then solubilized in water so as to eliminate the insolubles and to obtain an extract in the form of a protein concentrate.
• the method may also comprise, after step c) of precipitation, an additional step d) of decantation so as to allow better precipitation of the proteins, for example as described in Example 1c.
• this step is carried out at a temperature below room temperature, preferably at 4 D C, more preferably for at least 6:00, especially overnight.
• a step e) can be carried out after step b) comprising contacting the aqueous crude extract obtained in step b) with carboxymethylcellulose, advantageously during lhOO, especially at room temperature, so as to load it with the protein extract.
• This step may be followed by a step f) of contacting the charged carboxymethylcellulose obtained with step e) with an aqueous saline solution, advantageously an NaCl solution, having a pH greater than 7, advantageously 7.5, and then recovering the eluate thus obtained, which corresponds to a partially purified extract.
• the protein extract of non-germinated seed deoiled Moringa oleifera is advantageously an extract of shelled seeds, that is to say advantageously an extract of kernel seeds only (without its shell or shell).
• the method may therefore comprise a step prior to step a) of shelling the seeds.
• the extracts obtained can be centrifuged and / or filtered and / or distilled, so as to recover the water-soluble fraction and be in liquid form.
• the supernatant obtained after centrifugation is filtered, advantageously at a cut-off point of 0.45 mhi. Additional steps of bleaching and / or deodorization can be performed on the extracts at any stage of the extraction and according to the techniques known to those skilled in the art.
• the extracts may be discolored with activated charcoal.
• the extract according to the invention is obtained by extraction of ungerminated seed cake, in particular deoiled, more advantageously delipidated, in an aqueous saline solution at a pH of about 5 followed by elimination of the proteins. high molecular weight.
• the supernatant is recovered and constitutes an extract according to the invention.
• the extracts may also be concentrated by evaporation of the solvent or dried for example by lyophilization or by spraying.
• the extracts will then be in powder form.
• the Moringa oleifera extract obtained will be sterilized.
• the unprocessed seed protein extract deoiled from Moringa oleifera contains, on the basis of the dry extract, a protein content, in particular of native proteins, of between 0.01 and 100% by weight. weight, advantageously at least 25% by weight, in particular at least 40% by weight, more particularly at least 45% by weight.
• the proteins of the protein extract according to the invention advantageously have a molecular weight of between 6500 and 13000 Da, advantageously between 7100 and 11000 Da, measured by chromatography.
• the ungried seed extract of Moringa oleifera contains no alkaloid (such as, for example, spirochin), Pterygospermin, isothiocyanates (such as, for example, 4-2-L-Rhamnosyloxy benzyl). isothiocyanate) and kaempferol.
• alkaloid such as, for example, spirochin
• Pterygospermin such as, for example, Pterygospermin
• isothiocyanates such as, for example, 4-2-L-Rhamnosyloxy benzyl. isothiocyanate
• kaempferol such as, for example, kaempferol.
• the extract according to the invention may be used in the form of a cosmetic or pharmaceutical ingredient intended to be incorporated in a cosmetic or pharmaceutical composition, and further comprising a suitable cosmetic or pharmaceutical vehicle.
• the extract according to the invention is in another embodiment preferentially solubilized in and / or diluted in a particularly polar solvent, such as water, advantageously further comprising glycerin as in the product marketed under the name purisoft ® and in particular as described in Example 4a).
• a particularly polar solvent such as water
• the extract according to the invention in another embodiment can be atomized on an atomization support such as maltodextrin and be in the form of a powder in particular as described in Example 4b).
• the extract according to the invention is present in the ingredient in one content between 0.01 and 10% by weight of dry matter relative to the total weight of the ingredient, preferably between 1 and 5% by weight.
• the extract according to the invention is present in the ingredient in a content of between 10 and 60% by weight of dry matter relative to the total weight of the ingredient, preferably between 30 and 50% by weight.
• the extract according to the invention may also be in the form of a cosmetic or pharmaceutical composition, advantageously intended for topical or oral administration, in particular by way of administration. topically, preferably cutaneous, further comprising a suitable cosmetic or pharmaceutical vehicle.
• the cosmetic or pharmaceutical ingredient, in particular dermatological ingredient in liquid form and in particular that of Example 4a) may be used in a cosmetic or pharmaceutical composition, in particular a dermatological composition, preferably at a content by weight of dry matter relative to the weight total of the composition of between 0.01 and 10%, advantageously between 0.1 and 5%, in particular between 1 and 3%.
• the cosmetic or pharmaceutical ingredient in particular dermatological in solid form and in particular that of Example 4b), may be used in a cosmetic or pharmaceutical composition, in particular dermatological, preferably at a content by weight of dry matter relative to the weight total of the composition of between 0.001 and 5%, advantageously between 0.01 and 1%.
• the extract will be included in the cosmetic or pharmaceutical composition in a content of between 0.0001% and 20% by weight of dry matter relative to the total weight of the composition, preferably between 0.001% and 10% by weight, advantageously between 0.01 and 5% by weight.
• compositions according to the invention may contain any suitable solvent and / or any suitable vehicle and / or any suitable excipient, optionally in combination with other compounds of interest. They may in particular contain a cosmetically or dermatologically acceptable excipient selected from surfactants, preservatives, buffering agents, blowing agents, chelating agents, biocides, denaturants, opacifying agents, pH adjusters, reducing agents. , stabilizing agents, emulsifiers, thickeners, gelling agents, film-forming polymers, solvents, fillers, bactericides, odor absorbers, mattifying agents, conditioners, texturizing agents, gloss agents , pigments, dyes, fragrances and sunscreens chemical or mineral, trace elements, essential oils, sweeteners, flavor modifiers. These combinations are also covered by the present invention.
• CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes various cosmetic and pharmaceutical ingredients commonly used in the cosmetic and pharmaceutical industry, which are particularly suitable for oral administration and / or topical use.
• the excipient or excipients are chosen from the group comprising polyglycerols, esters, polymers and cellulose derivatives, lanolin derivatives, phospholipids, lactoferrins, lactoperoxidases, sucrose stabilizers, vitamin E and its derivatives, xanthan gums, natural and synthetic waxes, vegetable oils, triglycerides, unsaponifiables, phytosterols, silicones, protein hydrolysates, betaines, aminoxides, plant extracts, sucrose esters , titanium dioxides, glycines, and parabens, and more preferably from the group consisting of steareth-2, steareth-21, glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, methylparaben, ethylparaben, propylparaben, butylparaben, butylene glycol, caprylyl glycol, natural tocopherols, glycerin, dihydroxy
• the cosmetic or pharmaceutical composition or the extract according to the invention may be in any of the galenical forms conventionally used for topical application or oral administration, in particular topical administration such as liquid forms or solids or even in the form of pressurized liquid.
• aqueous or oily solution an aqueous cream or gel or an oily gel, in particular in a pot or in a tube, in particular a shower gel, a shampoo, a milk, an emulsion, a hydrogel, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone, a serum, a lotion, in particular in a glass or plastic bottle or in a measuring or aerosol flask, an ampoule, a liquid soap, a paste, a dermatological bread, an ointment, a mousse, an aerosol, a mask, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of a stick, in particular as a stick or in powders, especially makeup.
• the composition is in the form of a serum, a lotion, a cream, a milk, an ointment, a paste, a mousse, an emulsion, a hydrogel, a shower gel, a mask, a stick of a patch, or makeup powders, preferably a cream or a lotion.
• the cosmetic or pharmaceutical composition or the extract according to the invention may be in the form of a toothpaste or a dental paste. , a mouthwash, a lotion, an aerosol, a gel, a sucking tablet, an orodispersible tablet, a chewing gum or a mucoadhesive composition.
• the cosmetic or pharmaceutical composition may furthermore comprise other active ingredients for the treatment of skin and / or mucous membranes of sensitive and sensitized skin, skin and / or mucosa, which are sensitive, reactive, fragile and / or weakened and / or have an effect on the skin.
• cosmetic agents intended for the care of sensitive skin such as a plant extract of Cestrum latifolium as described in application WO2009 / 112590, for example marketed under the name of Symbiocell TM by the applicant, a butter extracted from the fruit of the tree Irvingia gabonensis marketed under the name Irwinol TM by the applicant, an extract of Eperua falcata root marketed under the name of Eperuline TM, an N-acetyl-L-Tyrosyl-L-Prolyl-L-Phenylalanyl-L-Phenylalaninamide peptide (INCI: acetyl tetrapeptide 15) sold under the name of Skinasensyl TM by the applicant.
• a plant extract of Cestrum latifolium as described in application WO2009 / 112590
• Symbiocell TM by the applicant
• a butter extracted from the fruit of the tree Irvingia gabonensis marketed under the name I
• the cosmetic composition may also contain one or more other active ingredients on the cutaneous and / or mucosal microbial flora and / or active on the barrier function of the skin, in particular moisturizing and / or soothing active agents, among which an oligosaccharide obtained by marketed enzymatic synthesis.
• the subject of the invention is also a cosmetic treatment method for the treatment of sensitized, fragile and / or fragile skins and / or mucous membranes to prevent and / or treat its unsightly and / or unpleasant manifestations and / or uncomfortable, especially chosen from redness, sensation of warmth or warmth or tension, tingling, tingling, tightness and a mixture of these manifestations, and / or for the increase and / or protection and / or maintenance of beneficial flora commensal in the skin and / or mucous membranes, in particular to prevent and / or reduce and / or delay the unsightly and / or unpleasant and / or uncomfortable manifestations of skin and / or mucosa whose commensal beneficial flora is impaired, in particular particularly for preventing and / or reducing and / or delaying the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations such as for preventing and / or reducing and / or delaying the formation of black
• the present invention furthermore relates to a protein extract of non-germinated seed deoiled from Moringa oleifera, advantageously a protein extract of ungerminated seed delipidated, in particular a protein extract of deoiled cake, more particularly delipidated, of non-germinated seeds, more advantageously of non-germinated seed almonds, Moringa oleifera, for its use in the treatment of reactive, hyperreactive, and / or irritated skin and / or mucous membranes and / or in the treatment and / or prevention and / or reduction of occurrence pathologies related to skin and / or mucous membranes that are sensitive, sensitized, reactive, fragile, fragile, intolerant, hyperreactive and / or irritated, such as contact urticaria, irritative or allergic contact dermatitis, eczema, psoriasis, seborrheic or atopic dermatitis, and / or in the treatment and / or prevention of inflammation and
• the present invention also relates to a protein extract of non-germinated seed deoiled from Moringa oleifera, advantageously a non-germinated delipidated seed protein extract, in particular a protein extract of deoiled cake, more particularly delipidated, of non-germinated seeds, more advantageously of almonds non-germinated seeds, Moringa oleifera, for its use in the treatment and / or prevention and / or the reduction of the occurrence of pathologies related to an alteration of the commensal flora and / or mucosal flora beneficial, advantageously involving a decrease in the content of commensal beneficial skin and / or mucosal microorganisms and / or an increase in the content of pathogenic microorganisms, preferably in pathogenic bacteria, in particular Staphylococcus aureus and / or Propionibacterium acnes, advantageously pathologies chosen from the group consisting of infections, especially bacterial, skin and / or mucous membranes,
• pathogenic microorganism is intended to mean a microorganism present on the skin and / or the mucous membranes in a non-permanent (transient) manner or a microorganism which normally lives on the skin but which under certain conditions may become virulent.
• pathogenic resident opportunistic pathogen
• inducing or capable of inducing non-pathological alterations of the skin and / or mucous membranes such as skin imperfections such as, for example, redness, dandruff and / or hair loss and / or hair, swelling or even pimples and / or a burning sensation and / or localized heat accompanied by pain, pigmentation spots or scars for example following acne and therefore an inhomogeneity of the complexion, and may be involved in real skin diseases including skin infections, such as boils, folliculitis, abscesses, ulcers, sycosis, ecthyma, erysipelas, acne or impetigo, see pathological conditions, such as fungal infections (such as candidiasis or dermatophytosis) such as scabies, ringworm and fungal infections caused by Candida albicans, malassezia, Streptococci, Propionibacterium acnes, Staphyloc
• each example has a general scope.
• the temperature is expressed in degrees Celsius and the pressure is the atmospheric pressure.
• the Moringa extract is prepared according to the process described in patent EP1064008, in particular as described below:
• Moringa oleifera kernels obtained after husking the seeds and containing 33.4% (weight / weight) of oil are delipidated by two successive extractions at reflux in hexane and, after filtration, the flour is dried in an oven at 40 ° C. ° C and has a residual oil content of 2.5%.
• the supernatant is collected and then filtered through 0.45 ⁇ m to obtain 1.77 liter of yellow filtrate, containing 4.69% of dry extract and having a protein concentration measured by the Biuret technique of 21.54. g / l (ie a protein purity on the basis of the solids content of 45.92%).
• the extract is spray-dried and 65.72 grams of atomisate is obtained with an estimated protein content of 54.7% (N ⁇ 6.25).
• the chromatographic profile resulting from the Superose 12HR column gel permeation analysis of this extract shows a major fraction which represents 52% of the surface and corresponds to molecular weights between 7 800 and 11 000 Da. The presence of shoulders in this peak confirms the existence of several compounds and the range of molecular weights is close to that found in the literature for the monomers (6,500 and 7,000 Da) and the dimers (13,000 Da) of proteins flocculants of Moringa.
• the precipitate is then dissolved in 270 ml of distilled water (ie 10% of the initial volume) and the pH of the solution is continuously adjusted to 4.5 with 6N HCl so as to allow the solubilization of the precipitate (the dispersion is facilitated by the use of a device of the type known as Turax).
• the almond oil obtained by peeling the seeds of Moringa oleifera is extracted by pressing on a press of the type known under the designation KOMET and the cake obtained is crushed in order to obtain a homogeneous flour.
• a crude extract is prepared from 1.24 kg of cake according to the procedure described in Examples 1a and 1b.
• Proteins are precipitated at pH 11.8 according to Example 1b, but an additional step of decanting overnight at + 4 ° C is introduced to allow better protein precipitation.
• the precipitate is treated under the same conditions as in Example lb (the pH of the solution for reconstituting the precipitate is however 6 instead of 4.5).
• the protein concentrate thus obtained (1.05 liter to 4.59% dry extract) is dehydrated by atomization and 34.6 g of atomisate are collected, ie an atomization efficiency on the basis of the dry extract of 71.5%.
• the protein content based on the nitrogen assay (N x 6.25) is greater than 90% (about 95%).
• a crude extract is prepared from 150 g of cake according to the procedure described in Examples 1a, 1b and 1c.
• CM52 Carboxymethylcellulose
• WHATMAN Carboxymethylcellulose
• the mixture is filtered on Buchner equipped with a # 42 WHATMAN filter, then the cellulose is collected and equilibrated again in 500 ml of water at pH 7.5.
• the cellulose After removal of the aqueous medium by filtration, the cellulose is brought into contact, with stirring for one hour at room temperature, with the aqueous extract of almond cake Moringa oleifera.
• the non-adsorbed compounds (fractions whose chromatographic profile is shown in broken lines in FIG. 3) are removed by filtration on Buchner and the "charged" cellulose is then washed twice with one liter of distilled water at pH 7.5. then filtered on Büchner.
• the cellulose is then contacted with 120 ml of a 60 g / l NaCl solution pH 7.5 for 30 minutes.
• the proteins eluted in NaCl medium are recovered by Buchner filtration (the chromatographic profile of the proteins adsorbed on CM 52 and eluted in NaCl medium 60 g / l is shown in solid line in Figure 3).
• the Superose 12HR column gel permeation analysis of this extract shows a major fraction which represents 70% of the surface and which corresponds to molecular weights of about 7,100 Da.
• the solution can be desalted by dialysis, or by ultrafiltration and dehydrated by lyophilization, atomization or any other suitable means.
• the extract was atomized on maltodextrin support and formulated according to Example 4b) to be tested in the following examples.
• Example 1d The product tested is that of Example 1d) formulated in the form of the ingredient according to Example 4b and used at 0.03% by weight relative to the total final medium (medium + product).
• the test is carried out on human keratinocytes HacaT in culture.
• the HacaT keratinocytes are inoculated at 2 ⁇ 10 6 cells / cm 2 in DMEM medium (Dulbecco's Modified Eagle Medium) supplemented with 10% S VF (Serum fetal calf). The cells are incubated for 3 to 5 days at 37 ° C. under 5% CO 2 and 95% relative humidity. The DMEM medium is then replaced with 1mL of Eagle's Minimum Essential Medium (EMEM). The product to be tested is then added the desired concentration in EMEM medium and the whole is incubated an additional day until saturation of the cell layer.
• DMEM medium Dulbecco's Modified Eagle Medium
• S VF Serum fetal calf
• 0.1 ml of a Staphylococcus aureus bacteria solution DSMZ 20231 ATCC 12600 (1.5x10 7 ) is added to each well for 2 hours at 37 ° C, 5% CO 2 aerobically, at relative humidity saturation. Then the media with bacteria are replaced by EMEM containing the product to be tested. The whole is again incubated for 24 hours at 37 ° C. and 5% of C0 2 .
• the IL8 and IL6 assays are performed according to the recommendations of the supplier of the ELISA kit.
• Table 2.1 Evaluation of the effect of the product according to the invention on the release of cytokine IL6 induced in keratinocytes by the presence of S. aureus
• Table 2.2 Evaluation of the effect of the product according to the invention on the release of cytokine ILS induced in keratinocytes by the presence of S. aureus
• IL8 caused by pathogenic bacteria 5. aureus in keratinocytes in culture. This demonstrates the effect of the product to treat sensitive skin, reactive, fragile, weakened, or sensitized and its anti-inflammatory effect.
• Example 3 Selective effects of the product on the growth of commensal microorganisms vis-à-vis opportunistic pathogenic microorganisms
• the product of the invention has a selective action on the growth of microorganisms of the skin.
• the product promotes the growth of commensal microorganisms and especially the bacteria that help the skin to fight inflammation such as Staphylococcus epidermidis and Acinetobacter Iwolffii.
• Example 3-a Inhibition of the growth of opportunistic pathogenic strain of
• Example 1d The product tested is that of Example 1d) formulated in the form of the ingredient of Example 4b) at 0.0006% and 0.006% by weight relative to the weight of the total final medium (medium and product).
• the ingredients are diluted in the culture medium of the bacteria (brucella broth).
• the media containing the ingredients are then incubated for 48 hours at 35 ° C. ⁇ 2.5 ° C. under anaerobic conditions with a calibrated inoculum of 5 ⁇ 10 5 P. acnes ATCC 11827. Growth is estimated by measuring the density optics at 600nm after incubation.
• Table 3.1 Evaluation of the effect of the product at different dosages on the growth of
• Example 3-b Activation of the Growth of Commensal Strains to Control S. epidermidis and / or ⁇ Iwolffii Inflammation
• Example 1d formulated in the form of an ingredient according to Example 4b) at 0.0006% and 0.006% by weight relative to the weight of the total final medium (medium and product).
• a cosmetic or pharmaceutical liquid ingredient having the following formulation in percent by weight is prepared.
• EXAMPLE 5 Composition according to the invention in the form of a lotion for the body and / or face:
• the lotion is prepared by the usual methods in the field well known to those skilled in the art, by mixing the 6 phases.
• EXAMPLE 6 Composition according to the invention in the form of a milk for the body and / or face
• a cosmetic product in the form of milk for the body and / or face may, for example, have a weight composition, consisting of the following aqueous and fatty phases, as indicated below.
• the fatty phase at 8 ° C., to bring the water of the aqueous phase also to 80 ° C. and to dissolve the preservative therein (Elestab 4112), then to pour the aqueous phase into the fatty phase with turbine stirring and to cool gradually stirring, to then add thereto, around 50 ° C, the aqueous mother solution of Moringa protein extract, then the perfume and, finally, to continue stirring until complete cooling.
• EXAMPLE 7 Composition according to the invention in the form of a cream for the face
• a cosmetic product in the form of a cream for the body and / or face may, for example, have a weight composition, consisting of the following aqueous and fat phases, as indicated below.

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• 2018
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