Classifications

• • 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)
  • A61K36/82—Theaceae (Tea family), e.g. camellia
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS OR COOKING OILS
  • A23D9/00—Other edible oils or fats, e.g. shortenings or cooking oils
  • A23D9/007—Other edible oils or fats, e.g. shortenings or cooking oils characterised by ingredients other than fatty acid triglycerides
• • 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
• • 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
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
  • C11B3/00—Refining fats or fatty oils
  • C11B3/006—Refining fats or fatty oils by extraction
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
  • C11B3/00—Refining fats or fatty oils
  • C11B3/10—Refining fats or fatty oils by adsorption
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
  • C11B3/00—Refining fats or fatty oils
  • C11B3/12—Refining fats or fatty oils by distillation
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
  • C11B3/00—Refining fats or fatty oils
  • C11B3/12—Refining fats or fatty oils by distillation
  • C11B3/14—Refining fats or fatty oils by distillation with the use of indifferent gases or vapours, e.g. steam

Definitions

• the invention relates to a lipid extract of Camellia oleifera tea oil, concentrated in its unsaponifiable fraction, as well as a cosmetic, nutraceutical, pharmaceutical or dermatological composition comprising a suitable excipient and said lipid extract.
• the invention also relates to a process for preparing a lipid extract of Camellia oleifera tea oil, concentrated in its unsaponifiable fraction.
• the invention also relates to such a composition or such an extract for its use in the prevention or treatment of disorders or pathologies of the skin, mucous membranes or appendages.
• the invention finally relates to a cosmetic care process for the skin, appendages or mucous membranes, with a view to improving their condition or appearance, consisting in administering such a composition or such an extract, in particular in order to improve the physical/physiological and psychological well-being of the user.
• Camellia The genus Camellia is native to eastern Asia and includes more than 200 evergreen woody species. Some species have significant economic value, such as C. sinensis, C. japonica, and C. oleifera.
• C. sinensis is grown mainly in tropical and subtropical regions for tea
• C. japonica is grown in temperate regions as an ornamental plant, and its oil is traditionally used as a cosmetic in Japan.
• C. oleifera also known as “oil-tea camellia,” can grow on barren land without fertilizer, start producing fruit six years after initial planting, and remain highly productive for 80 years. This species is mainly cultivated in China for the production of edible oils (“camellia oil,” “tea seed oil”) (Yang et al., 2016).
• the amount of oil contained in seeds and the fatty acid composition may vary depending on the variety, soil, and climate (Hu & Yang, 2018). Wen et al. (2016) estimated that light intensity during fruit development and ripening (July–October) influences fruit yield and quality.
• Camellia oleifera oil is used in cooking. It is also traditionally used to treat stomach aches and burns. Because of its monounsaturated fatty acid content (C18:l majority) similar to olive oil, several studies have been conducted to determine whether it could be attributed the same health benefits, particularly in reducing cardiovascular risks. Studies have highlighted the ability of tea oil to reduce the content of cholesterol, triglycerides and low-density lipoproteins, as well as thromboxane B2 and products due to lipid peroxidation. It also increases the activity of superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px). Some of these activities could be due to the presence of saponins.
• SOD superoxide dismutases
• GSH-Px glutathione peroxidase
• lipid extracts are used as such, for their specific properties.
• the Applicant has thus surprisingly discovered that the lipid extract of Camellia oleifera tea oil, concentrated in its unsaponifiable fraction, can be used to stimulate, restore or regulate the metabolism of skin and mucous membrane cells and/or for its use in the prevention and/or treatment of disorders related to skin tissue.
• the invention relates to a lipid extract of tea oil, said lipid extract being a Camellia oleifera tea oil, concentrated in its unsaponifiable fraction, containing from 1.5% to 100% by weight of unsaponifiables, preferably 1.8% to 80%, preferentially 2% to 60%, relative to the total weight of the extract.
• the invention relates to a process for preparing said extract comprising the following successive steps: a) molecular distillation of a crude or refined Camellia oleifera tea oil; b) where appropriate, extraction of the unsaponifiable; c) recovery of the oil concentrated in unsaponifiable obtained following step a) or of the unsaponifiable obtained following step b); d) optionally a step of deodorization and/or decolorization of the oil concentrated in unsaponifiable or of the unsaponifiable.
• step b) comprises the following successive steps: i. saponification of the concentrated tea oil into its unsaponifiable fraction obtained following step a), ii. then extraction of the unsaponifiable using a suitable solvent, such as ethyl acetate and hexane.
• a suitable solvent such as ethyl acetate and hexane.
• the invention relates to a composition
• a composition comprising, as active ingredient, said lipid extract of tea oil and a suitable excipient.
• the composition may be cosmetic, nutraceutical, pharmaceutical or dermatological.
• the invention relates to the extract according to the invention or a composition comprising the extract according to the invention or the extract capable of being obtained by the process according to the invention, for its use in a dermatological or pharmaceutical composition.
• the invention relates to the use of the extract according to the invention or of a composition comprising the extract according to the invention or the extract capable of being obtained by the process according to the invention, in a nutraceutical composition or as a food supplement.
• the invention relates to a cosmetic care method for the skin and/or appendages and/or mucous membranes with a view to improving their condition and/or their appearance, comprising the topical or oral administration of an extract according to the invention or of a composition according to the invention.
• the invention relates to a method of cosmetic treatment of dry skin, xerosis, sensitive skin, irritated skin, comprising the administration, by topical or oral route, of an extract according to the invention or of a composition according to the invention.
• the subject of the invention is a lipid extract of tea oil, said lipid extract being a Camellia oleifera tea oil concentrated in its unsaponifiable fraction, containing from 1.5% to 100% by weight of unsaponifiables, preferably 1.8% to 80%, preferentially 2% to 60%, relative to the total weight of the extract.
• Unsaponifiable matter is the fraction of a fatty substance which, after prolonged action of an alkaline base, remains insoluble in water and can be extracted by an organic solvent.
• Five major groups of substances are present in most unsaponifiable matter of vegetable oils: saturated or unsaturated hydrocarbons, aliphatic or terpenic alcohols, sterols, tocopherols, tocotrienols, carotenoid pigments and xanthophylls.
• the oil is concentrated in its unsaponifiable fraction, in particular it comprises more than 1.5% by weight of unsaponifiables, relative to the total weight of the extract, advantageously more than 2%, preferably more than 2.5% by weight of unsaponifiables.
• the lipid extract of Camellia oleifera tea oil advantageously comprises fatty acids having from 12 to 22, more advantageously from 16 to 20, carbon atoms. These fatty acids can be saturated, monounsaturated or polyunsaturated.
• This concentrate is advantageously obtained from a refined tea oil.
• the oil can be refined according to processes known to those skilled in the art such as physical refining (degumming with water, deacidification by steam stripping deodorization) and chemical refining (demucilagination with water or acid treatment in order to eliminate phospholipids, neutralization of free fatty acids using a basic solution, decolorization, refrigeration and deodorization), in particular by steam stripping deodorization.
• An example of characteristics of the refined Camellia oleifera tea oil is given in the following table.
• Camellia oleifera tea oil is advantageously concentrated into its unsaponifiable fraction - the "concentrate", typically by molecular distillation.
• the oil concentrated in its unsaponifiable fraction advantageously presents the following specifications.
• the ⁇ -tocopherol content is greater than 60% by weight, relative to the total weight of tocopherols, preferably 80% by weight, preferentially 95% by weight.
• the sterol content of the extract according to the invention is greater than 1.5% by weight, preferably 2%, relative to the total weight of the extract.
• the lipid extract according to the invention advantageously contains p-amyrin and A5-avenasterol, preferably from 10 to 50% by weight, preferentially from 15 to 40%, more preferentially from 15 to 35% by weight, typically from 20 to 35% by weight, relative to the total weight of sterols and/or lupeol and A7-stigmasterol, preferably from 10 to 50% by weight, preferentially from 15 to 40%, more preferentially from 15 to 35% by weight, typically from 20 to 35% by weight, relative to the total weight of sterols.
• p-amyrin and A5-avenasterol preferably from 10 to 50% by weight, preferentially from 15 to 40%, more preferentially from 15 to 35% by weight, typically from 20 to 35% by weight, relative to the total weight of sterols.
• the lipid extract according to the invention comprises:
• the extract according to the invention is advantageously obtained by a process comprising the following successive steps: a) molecular distillation of a crude or refined Camellia oleifera tea oil; b) where appropriate, extraction of the unsaponifiable matter; c) recovery of the oil concentrated in unsaponifiable matter obtained following step a) or of the unsaponifiable matter obtained following step b); and d) optionally a step of deodorization and/or decolorization of the oil concentrated in unsaponifiable matter or of the unsaponifiable matter.
• step b) When it is desired to recover the oil enriched (concentrated) in unsaponifiable matter, step b) is not implemented. When it is desired to recover the unsaponifiable fraction, step b) is implemented.
• This step b) advantageously comprises the following successive steps: i. saponification of the concentrated tea oil into its unsaponifiable fraction obtained following step a), ii. then extraction of the unsaponifiable using a suitable solvent, such as ethyl acetate and hexane.
• a suitable solvent such as ethyl acetate and hexane.
• the invention also relates to a process for preparing an extract according to the invention comprising the following successive steps: a) molecular distillation of a crude or refined Camellia oleifera tea oil; b) where appropriate, extraction of the unsaponifiable; c) recovery of the oil concentrated in unsaponifiable obtained following step a) or of the unsaponifiable obtained following step b); d) optionally a step of deodorization and/or decolorization of the oil concentrated in unsaponifiable or of the unsaponifiable.
• the molecular distillation step a) is preferably carried out using a device selected from centrifugal type molecular distillers and scraped film type molecular devices.
• Centrifugal type molecular distillers are known to those skilled in the art.
• application EP 493 144 describes a molecular distiller of this type.
• the product to be distilled is spread in a thin layer on the heated surface (surface hot) of a conical rotor rotating at high speed.
• the distillation enclosure is placed under vacuum. Under these conditions, there is evaporation and not boiling, from the hot surface, of the constituents of the oil such as the unsaponifiables, the advantage being that the oil and its constituents, in particular the unsaponifiables (these products being known to be fragile), are not degraded during evaporation.
• Scraped film molecular distillers are also known to those skilled in the art. Generally, they comprise a distillation chamber equipped with a rotating scraper, allowing the continuous spreading on the evaporation surface (hot surface) of the products to be distilled. The product vapors are condensed by means of a refrigerated finger, placed in the center of the distillation chamber.
• the peripheral feed and vacuum systems are very close to those of a centrifugal distiller (feed pumps, vane and oil diffusion vacuum pumps, etc.). The recovery of residues and distillates is done by gravitational flow in the appropriate containers.
• the distilled fraction rich in unsaponifiables advantageously represents 3 to 15% by weight of the starting oil
• the distilled fraction rich in triglycerides advantageously represents 85 to 97% by weight of the starting oil.
• the product obtained may optionally be deodorized and/or decolorized by processes known to those skilled in the art, for example deodorized by steam stripping or molecular distillation, or decolorized by treatment on activated carbon.
• step b) is not carried out.
• step b) is carried out.
• This step advantageously comprises the following successive steps: i. saponification of the concentrated tea oil into its unsaponifiable fraction obtained following step a), ii. then extraction of the unsaponifiable using a suitable solvent, such as ethyl acetate and hexane.
• the unsaponifiable matter of tea oil can be obtained by methods known to those skilled in the art. For example, it can be obtained by carrying out saponification on the tea oil concentrated in its unsaponifiable fraction, then by extracting this unsaponifiable matter using a suitable solvent. Typically, the unsaponifiable matter is then washed until the soaps are completely removed and then the solvent is evaporated. Finally, the unsaponifiable matter advantageously undergoes deodorization with water vapor and then stripping with nitrogen in order to remove traces of solvent.
• the unsaponifiable tea oil thus obtained advantageously presents the characteristics described above.
• extract according to the invention designate the extract as such, as defined above, or the extract capable of being obtained by the process according to the invention as described above.
• Another subject of the invention relates to a composition
• a composition comprising, as an active ingredient, a lipid extract of Camellia oleifera tea oil according to the invention.
• composition according to the invention advantageously comprises from 0.01% to 20%, advantageously from 0.05 to 15%, more advantageously 0.1 to 10%, by weight of said lipid extract, relative to the total weight of the composition.
• the lipid extract according to the invention is advantageously used as an active agent in a composition such as a cosmetic, nutraceutical, dermatological or pharmaceutical composition, which may comprise one or more suitable excipients.
• composition according to the invention can be formulated in the form of different preparations suitable for topical or oral administration.
• the various preparations are suitable for topical administration and include in particular creams, emulsions, milks, ointments, lotions, oils, aqueous or hydro-alcoholic or glycolic solutions, powders, patches, sprays, shampoos, varnishes or any other product for external application.
• composition is advantageously formulated in the form of a preparation suitable for topical administration.
• the composition is advantageously formulated in the form of a preparation suitable for oral administration.
• the extract according to the invention can be included either in a food supplement or in a nutraceutical composition.
• the food supplement can be in the form of the extract according to the invention as such or in the form of gelatin or vegetable capsules or soft capsules. Said food supplement can then contain from 10 to 100% by weight of the extract according to the invention.
• composition of the present invention can be incorporated directly and without further modification into nutraceuticals, dietary products, particularly high-protein products, or beverages, using techniques such as mixing, infusion, injection, blending, absorption, kneading and spraying.
• composition according to the invention may also contain the usual adjuvants in the pharmaceutical, dermatological, cosmetic or nutraceutical fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, thickeners, preservatives, antioxidants, solvents, perfumes, chelating agents, odor absorbers, chemical or mineral filters, mineral pigments, surfactants, polymers, silicone oils and coloring matters.
• the amounts of these different adjuvants are those conventionally used in the fields considered, 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, into the aqueous phase, into the lipid vesicles and/or into the nanoparticles. The person skilled in the art is able to choose the appropriate adjuvants according to the intended application.
• oils that can be used in the compositions for implementing the invention mention may be made of mineral oils, oils of plant origin (apricot oil, sunflower oil, plum oil), oils of animal origin, synthetic oils, silicone oils and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids and waxes (beeswax) may also be used as fats.
• emulsifiers and co-emulsifiers which can be used in the invention, mention may be made, for example, of fatty acid and polyethylene glycol esters such as PEG-40 stearate, PEG-100 stearate, fatty acid and polyol esters such as glyceryl stearate and sorbitan tristearate.
• hydrophilic gelling agents mention may be made in particular of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes.
• compositions according to the invention can be determined according to the criteria generally taken into account in establishing a pharmaceutical, dermatological or cosmetic treatment adapted to a patient, such as for example the extent of the area of skin to be treated, tolerance to the treatment, skin type.
• the invention also relates to the use of an extract according to the invention or of a composition according to the invention as a food supplement or in a nutraceutical composition.
• the invention also relates to an extract according to the invention or a composition according to the invention for its use as, or in, a dermatological or pharmaceutical composition.
• composition or extract according to the invention can be used to stimulate, restore or regulate the metabolism of skin and mucous membrane cells and/or in the prevention and/or treatment of disorders related to skin tissue.
• the composition or extract according to the present invention is used in the prevention and/or treatment of disorders or pathologies of the skin and/or mucous membranes and/or appendages.
• the disorders or pathologies of the skin and/or mucous membranes and/or appendages are chosen from inflammatory reactions, disorders linked to intrinsic or extrinsic stress such as psychological stress, stress linked to a state of anxiety, stress linked to radical attacks linked or not to chemical or atmospheric pollution, and/or linked to exposure to UV or IR, disorders of the barrier or homeostasis, photosensitized skin, mechanical and/or thermal aggressions, or as a healing agent.
• disorders or pathologies of the skin and/or mucous membranes and/or appendages can also be chosen from those caused by imbalances in the microbiota; they are advantageously chosen from atopic dermatitis, eczema, the development of bad axillary odors, weakening of the skin barrier, acne, psoriasis, hidradenitis suppurativa, folliculitis, cradle cap, dandruff, itching, particularly of the scalp, irritation, candidiasis and bacterial vaginosis.
• the inflammatory, irritative reactions, disorders or pathologies or disorders of the barrier or homeostasis of the skin are: acne, rosacea or erythrocouperose, vascular disorders, in particular redness and couperose, diaper dermatitis, atopic dermatitis, eczema, contact dermatitis, dermatitis irritant, allergic dermatitis, seborrheic dermatitis (cradle cap), sensitive skin, reactive skin, dry skin (xerosis), dehydrated skin, skin with redness, skin erythema, aged or photo-aged skin, photosensitized skin, pigmented skin (melasma, post-inflammatory pigmentation, etc.), skin with stretch marks, sunburn, irritation by chemical, physical (e.g. stress for pregnant women), bacteriological, fungal agents, skin aging, in particular photoaging and disorders linked to radical attacks linked to chemical or atmospheric pollution, and/or linked to exposure to UV or IR.
• acne rosacea or erythrocoup
• the disorders or pathologies of the skin and/or mucous membranes and/or appendages are chosen from dry skin, xerosis, sensitive skin and irritations.
• the invention also relates to an extract according to the invention or a composition according to the invention for preventing and/or treating dry skin, xerosis, sensitive skin, irritations, fragile lips, cheilitis, atopic dermatitis, eczema and psoriasis.
• These disorders may be skin disorders linked to intrinsic or extrinsic stresses such as psychological stress.
• composition or extract according to the invention advantageously makes it possible to improve skin comfort.
• the extract or composition according to the invention can be used as an anti-aging agent and/or healing agent; to prevent skin damage, and/or maintain homeostasis of the skin or mucous membranes or as an antioxidant and/or anti-inflammatory agent.
• the composition or extract according to the invention can be used to prevent or delay premature skin aging, in particular photo-induced, advantageously to prevent, reduce and/or treat wrinkles, fine lines or an alteration of the microrelief.
• composition or extract according to the invention can also be used to promote healing.
• the composition or extract according to the invention can also be used in the prevention and/or treatment of pathologies or conditions chosen from the group consisting of superficial scars, fragile lips and cheilitis, stretch marks, skin after bites, skin abrasions, pimples and/or skin scabs, and fragile and sensitive skin, advantageously fragile and sensitive skin.
• the invention also relates to the use of an extract according to the invention or of a composition according to the invention for the manufacture of a cosmetic, pharmaceutical or dermatological composition for preventing and/or treating disorders or pathologies of the skin and/or mucous membranes and/or appendages.
• the disorders or pathologies of the skin and/or mucous membranes and/or appendages are chosen from inflammatory reactions, disorders linked to intrinsic or extrinsic stresses such as psychological stress, stress linked to a state of anxiety, stress linked to radical attacks linked or not to chemical or atmospheric pollution, and/or linked to exposure to UV or IR, disorders of the barrier or homeostasis, photosensitized skin, mechanical and/or thermal aggressions.
• the invention further relates to a method for preventing and/or treating disorders or pathologies of the skin and/or mucous membranes and/or appendages, comprising the administration, in particular the topical administration, of an effective amount of an extract according to the invention or of a composition according to the invention, to a subject in need thereof.
• the disorders or pathologies of the skin and/or mucous membranes and/or appendages are as defined above.
• Another subject of the invention relates to a non-therapeutic cosmetic care method for the skin and/or appendages and/or mucous membranes with a view to improving their condition and/or their appearance, advantageously with a view to improving the firmness, elasticity or tone of the skin, comprising the topical or oral administration of an extract or a composition according to the invention.
• Said cosmetic care method is preferably carried out with a view to improving skin comfort, typically on healthy skin, healthy appendages or healthy mucous membranes, particularly advantageously for treating and/or preventing dry skin, xerosis, sensitive skin and irritated skin.
• the cosmetic uses and cosmetic care methods according to the present invention are typically carried out on healthy skin or healthy parts of the body and are not therapeutic.
• Another subject of the invention relates to a method of cosmetic treatment of dry skin, xerosis, sensitive skin, irritated skin, comprising the administration, by topical or oral route, of an extract or a composition according to the invention.
• Fig. 1 Active vs placebo results for each of the ten parameters of the “sensitive scale” (left: active, right: placebo).
• An example of a concentrate according to the invention is a refined oil of Camellia oleifera concentrated in its unsaponifiable fraction.
• the extract is prepared by molecular distillation. Vacuum condition: 10 -2 to 10 -3 mbar
• Distillation body temperature between 250 and 280 °C The mass distribution is shown in the table below.
• Example 2 In vitro biological activity tests of the extract according to the invention
• the extract tested is the concentrate of Example 1. It will be referred to in the studies as “tea oil concentrate”. Unless otherwise indicated, the percentages are expressed as the weight of concentrate relative to the total weight of the composition tested.
• TSA tea oil concentrate
• keratinocytes Normal human keratinocytes were pre-incubated for 24 hours in the presence of 0.001%, 0.005% or 0.01% tea tree oil concentrate or 0.1 ⁇ M dexamethasone, an anti-inflammatory reference. The cells were then stimulated by overnight treatment in the presence of 10 ⁇ g/mL PMA (Phorbol-Myristate-Acetate). At the end of treatment, the IL-1 alpha produced was quantified by ELISA assay in the culture supernatants.
• PMA Phorbol-Myristate-Acetate
• results were statistically analyzed by one-way analysis of variance (ANOVA), followed by Tukey post-test.
• Table 8 Dosage of interleukin-1 alpha produced by keratinocytes subjected to inflammatory stress induced by PMA
• Reconstructed epidermis were treated topically with a formulation (cream) containing 1% tea tree oil concentrate or its placebo, or systemically with 1 ⁇ M dexamethasone, an anti-inflammatory reference. After 24 hours of pre-incubation, the epidermis were stimulated with 0.5 ⁇ g/mL PMA and incubated again for 24 hours. Culture subnatants were collected and IL-1 alpha assay was performed.
• Tea tree oil concentrate formulated at 1%, inhibits SDS-induced IL-1 alpha and IL8 release.
• Table 10 Dosage of IL-1 alpha produced by reconstructed epidermis stimulated by PMA
• Skin aging is characterized by an alteration of the dermal matrix, including a reduction in the quality and quantity of matrix fibers.
• tea oil concentrate The anti-aging activity of tea oil concentrate was evaluated by its ability to stimulate the expression and production of dermal matrix markers under standard conditions and under inflammatory stress conditions modeling “inflamm'aging”.
• Tea oil concentrate was evaluated in an in vitro model reproducing the "inflammaging” process: inflammation, represented by the stimulation of IL-1 alpha production, is induced on reconstructed epidermis. Conditioned media from these reconstructed epidermis are then applied to fibroblasts and the expression of dermal markers, altered by IL-1 alpha produced by the epidermis, is evaluated. Material and method
• Reconstructed epidermis were treated topically with a formulation (cream) containing 1% tea tree oil concentrate or its placebo, or systemically with 1 ⁇ M dexamethasone, an anti-inflammatory reference. After 24 hours of pre-incubation, the epidermis were stimulated with 0.5 ⁇ g/mL PMA and incubated again for 24 hours.
• Tea oil concentrate formulated at 1%, significantly inhibited PMA-induced IL-1 alpha release in reconstructed epidermis. This effect was significantly different from placebo.
• tea oil concentrate modulated the overexpression of cytokines and chemokines (CXCL1, IL8, IL6, CCL2), matrix degrading enzymes (MMPI, MMP3) and increased the gene expression level of HAS2.
• CXCL1, IL8, IL6, CCL2 cytokines and chemokines
• MMPI, MMP3 matrix degrading enzymes
• Table 13 Genes modulated by the 1% Tea Oil Concentrate formula in the “Inflamm'aging” model: gene expression in fibroblasts incubated in the presence of conditioned media
• HAS2 100 78 104 100 (100%) 150 (327%) extracellular matrix
• a formulation (cream) containing 1% tea tree oil concentrate, or its placebo, was applied to the surface of reconstructed human skin. After 24 hours of incubation, Gene expression of markers of interest for their dermal benefits was assessed by
• Tea oil concentrate formulated at 1%, significantly increased the gene expression level of markers MKI67 and PSMD1. These effects were significantly different from placebo.
• Aging is associated with a decrease in the proliferative capacity of cells.
• a decrease in the expression of the MKI67 marker was observed in aged cells.
• tea oil concentrate can thus promote cell proliferation, thus demonstrating anti-aging potential.
• PSMD1 is a subunit of the proteasome that plays a key structural role by acting as a docking site for ubiquitinated substrates ready for clearance. A decrease in this marker has been observed in aged fibroblasts. The decreased ability of cells to clear damaged proteins is a marker of aging. By increasing the gene expression level of PSMD1, tea oil concentrate could promote the clearance of damaged proteins and thus demonstrate anti-aging potential.
• Table 14 Genes significantly modulated by 1% tea oil concentrate formulation compared to placebo (set at 1.00)
• a formulation (cream) containing 1% tea tree oil concentrate, or its placebo, was applied to the surface of reconstructed epidermis. After 24 hours of incubation, gene expression of markers of interest for their epidermal benefits was assessed by quantitative real-time PCR.
• Tea oil concentrate formulated at 1%, significantly increased the gene expression level of barrier markers (TJP1, DSC1, LOR, ZNF750, CERS3). These effects were significantly different from placebo demonstrating a pro-barrier potential of tea oil concentrate.
• Table 15 Genes significantly modulated by 1% tea oil concentrate formulation compared to placebo (set at 1.00)
• TJP1 Tight junction protein ZO-1 1.70 (+70%) 0.027
• Zinc finger protein 750 1.60 (+60%) 0.039
• CERS3 Ceramide synthase 3 1.33 (+33%) 0.048
• tight junctions secretor cells
• desmosomes secretor cells
• Tight junctions are intercellular junctions that seal keratinocytes together.
• the TJP1 protein is a marker of tight junctions. It participates in the control of paracellular diffusion of ions and solutes.
• Desmosomes are localized junctions between keratinocytes of the basal, spinous, and granular layers. Desmosomes consist of 3 parts: an intracellular part, a transmembrane part, and an extracellular part. Desmocollin-1 is a component of desmosomes. It is a transmembrane glycoprotein belonging to the cadherin family.
• Loricrin, ZNF50 and CERS3 markers are involved in the formation of the cornified envelope.
• the plasma membrane of differentiating keratinocytes is replaced by the cornified envelope consisting of insoluble structural extracellular proteins covalently linked to each other and to lipid remodeling. This prevents excessive loss of body fluids, but also provides an effective barrier against pathogens.
• 80% of the horny envelope is made up of loricrin.
• Keratinocyte differentiation is stimulated by many transcription factors such as ZNF50, a transcription factor known to regulate several genes encoding components of the corneal envelope and terminal differentiation of keratinocytes.
• ZNF50 a transcription factor known to regulate several genes encoding components of the corneal envelope and terminal differentiation of keratinocytes.
• Ceramides are the predominant lipids in the skin and constitute approximately 50% by mass of intercellular lipids. They participate in the skin barrier function and in maintaining hydration. Ceramide synthases (GERS) 3 and 4 are predominant in the skin.
• Tea oil concentrate by significantly increasing the level of gene expression of these different markers, thus contributes to a pro-barrier effect.
• Activity in in vitro models related to skin comfort and well-being related to skin comfort and well-being
• Psychological stress has multiple physiological and clinical impacts on the skin.
• the physiological impacts are varied (inflammation, alteration of the barrier function, alteration of healing, suppression of immunity) and will lead to clinical impacts (dry/sensitive skin phenotype, redness, irritation, itching, blemishes, acne, eczema, etc.).
• HPA axis Hypothalamic-pituitary-adrenal axis
• Acute psychological stress can alter the permeability of the skin barrier as well as the integrity of the stratum corneum.
• Skin explants were treated topically with a formulation (cream) containing 1% tea oil concentrate, or its placebo, or treated systemically (in the culture medium) with 0.001% tea oil concentrate and the positive reference metyrapone at 1 mM.
• the explants were incubated for 24 hours and then stressed with 0.6 ⁇ M ACTH (Adreno CorticoTropic Hormone), a hormone that induces cortisol production.
• ACTH Adreno CorticoTropic Hormone
• This stress was coupled with a culture of the explants in an incubator at 42 °C in order to potentiate the increase in cortisol production.
• the explants were again treated with the products topically or the active and the positive reference systemically. After 24 hours of incubation, the culture media were recovered and an ELISA assay for cortisol was performed.
• Tea tree oil concentrate formulated at 1% versus placebo, inhibited cortisol, with placebo increasing cortisol release.
• Table 16 Dosage of cortisol produced by skin explants stimulated by ACTH + T°C 42°C (Tea oil concentrate tested systemically in the culture medium)
• Table 17 Dosage of cortisol produced by skin explants stimulated by ACTH + T°C 42°C (Tea oil concentrate tested topically in formulation versus placebo)
• Tea oil concentrate was evaluated in a model of keratinocytes (HaCaT) stressed with cortisone and then UVA.
• UVA stress potentiates the transformation of cortisone (inactive molecule) into cortisol (active molecule). Cortisol is described to alter the skin barrier.
• HaCaT keratinocytes were treated with 0.0005% and 0.001% tea oil concentrate in parallel with 100 nM cortisone treatment. After 24 h of incubation, cells were stressed by UVA at 3 J/cm 2 . Cell lysates were collected either immediately after irradiation for analysis of carbonylated proteins by immunostaining or 6 h after irradiation for analysis of barrier and inflammation markers by RT-qPCR.
• Cortisone stress combined with UVA increased the gene expression level of IL-1 alpha, reflecting an activation of inflammation. It also increased the amount of carbonylated proteins. It inhibited the gene expression level of barrier markers (loricrin, filaggrin and keratin 10) demonstrating the negative impact of cortisol on the skin barrier.
• Tea oil concentrate showed a pro-barrier protective effect increasing the cortisol/UVA stress-inhibited markers filaggrin, loricrin and keratin 10. Tea oil concentrate also showed an anti-inflammatory effect towards IL1a (gene expression) and decreased the amount of stress-induced carbonyl proteins (damaged proteins). This last result can be correlated with a result observed during the activity screening on reconstructed skin where the tea oil concentrate significantly increased the level of gene expression of the marker PSMD1 (26S proteasome non-ATPase regulatory subunit 1), a marker of the proteasome involved in the degradation of damaged proteins.
• Stimulated cells (Cortisone 100 nM 128 ⁇ 10
• the stratum corneum of skin explant was altered by tape stripping followed by 0.001% cortisol stress. After 6 hours of incubation, the explants were treated on their surface with a formulation (cream) containing 1% tea tree oil concentrate, or its placebo. 24 hours after the first application (D1), the explants were again treated with cortisol and then the products 6 hours later. These treatments (cortisol + product 6 hours later) were repeated for a total of 5 treatments (D0 to D4). 24 hours after the last treatment (D5), the explants were recovered in order to perform different markings:
• Results were statistically analyzed using ANOVA followed by Tukey or Dunnett test.
• the tea oil concentrate tested at 1% versus placebo, shows significant efficacy on the thickness of the stratum corneum and the number of layers of the stratum corneum (histological marking) which are more important in the condition treated with the active ingredient. It also shows significant efficacy on the integrity of the skin barrier (penetration of the lucifer yellow marker).
• the tea oil concentrate thus promotes the repair of the skin barrier and protects against psychological stress which alters the repair of the skin barrier.
• tea oil concentrate is of great interest in the comfort of dry and sensitive skin which can be caused and amplified by psychological stress.
• Human iPS (induced pluripotent stem cells) cells were differentiated into sensory neurons in culture inserts. A collagen gel was then applied to the sensory neurons. After 3 weeks of culture, an explanted epidermis, dissociated from the dermis by dispase treatment, was deposited on the collagen gel. The model was incubated for 5 days, the time for the reinnervation of the epidermis by the sensory neurons. Then the epidermis was treated topically with tea oil concentrate formulated at 0.5% and 1% in paraffin. After 24 hours of incubation, the epidermis was treated topically with 10% lactic acid for 15 minutes. The culture media were then recovered and an ELISA assay for substance P was performed.
• Tea tree oil concentrate tested at 0.5% and 1%, significantly inhibits the release of substance P, a neuropeptide involved in pain perception, induced by lactic acid in a reinnervated epidermis model.
• Tea oil concentrate is therefore of interest in the comfort of sensitive skin.
• the objective of this study is to evaluate the efficacy and emotional benefit of the extract according to the invention in comparison with a placebo in people expressing psychological discomfort/stress/bad mood due to their dry skin and/or sensitive skin.
• the extract tested is the concentrate from example 1.
• the active ingredient is formulated at 1% tea oil concentrate.
• the details of the compositions are presented in the table below. Table 24:
• the “Sensitive Scale” described in the literature allows to assess the degree of overall skin irritation and the severity of the skin condition (Misery et al., 2014). This scale is made up of 10 items corresponding to signs felt (8 items) or apparent (2 items) related to skin discomfort: tingling, burning sensations, sensations of heat, tightness, itching, pain, general discomfort, hot flashes, redness and flaking.
• the subject can graduate the intensity of each parameter from 0 to 10.
• the improvement is significant between T0 and T28 with the active ingredient while it is only significant for 6 parameters for the placebo (see Figure 1).
• the active ingredient shows significantly improved results compared to the placebo. Indeed, the following three parameters are at the threshold of p ⁇ 0.05: tingling, burning sensation and itching. In addition, the following three parameters as well as the overall score are at the threshold of p ⁇ 0.1 (see Figure 2): sensations of heat, tightness and general discomfort.
• Prosody corresponds to the emotional content of the voice and can be appreciated by studying the vocal spectrum revealing variations in several parameters. Vocal stress load was quantified using algorithmic processing.
• the active ingredient significantly reduces vocal stress after 28 days and the evolution compared to the placebo is significantly better (see Figure 3).
• HRV Heart rate variability
• the active ingredient significantly increases cardiac coherence HRV after 28 days and the difference with the placebo is significantly better (see Figure 4).
• the electrodermal response corresponds to the variation in the resistance of the skin when the electric current passes through it. It is a response that occurs following sensory or emotional arousals. This variation in the skin's electrical resistance is the result of physiological changes that may be unconscious or imperceptible to the naked eye. These neuro-vegetative changes are the consequences of the activation of the sympathetic nervous system. Indeed, following psychological (i.e. emotional) excitement, the activity of the sweat glands increases which in turn increases the skin conductance leading to a very rapid EDR. This reaction occurs especially on the plantar and palmar areas. The sweat glands are controlled by the sympathetic nervous system through the fibers of the cholinergic ganglia. In this way, the electrodermal response can be used as a physiological sign of emotional arousal.
• Example 4 In vivo biological activity tests of the extract according to the invention Concept and protocol
• the aim of this study is to evaluate the efficacy and benefit of an active ingredient on skin condition in comparison with a placebo in people with dry and/or sensitive skin condition.
• the skin barrier plays a regulatory role in the skin's water balance. When the skin is damaged, there are disruptions in the regulation of water exchange. Water then migrates more easily to the external environment, which increases Transepidermal Water Loss (TEWL). On the other hand, if the condition of the skin barrier improves, water loss values will decrease because water exchange regulation will be ensured correctly.
• TEWL Transepidermal Water Loss
• the aim of this study is to evaluate the efficacy and benefit of an active ingredient on skin condition in comparison with a placebo in people with dry and/or sensitive skin condition.
• the extract tested is the concentrate from example 1.
• the active ingredient is formulated at 1% tea oil concentrate.
• the details of the compositions are presented in the table below.
• At least 50% of subjects with visibly dry skin on the face at least 50% of subjects with sensitive skin (assessed according to a literature questionnaire: Boyer et al., 2021) with 1 clinical sign and 1 subjective sign on at least 2 stresses.
• Transepidermal water loss measurements were performed with a Tewameter TM 300®. A probe composed of two sensors is crossed by a flow of water vapor. The partial pressure difference is measured between the two sensors. This value corresponds to the evaporation rate of a volatile substance (here water).

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