WO2015092227A1 - Use of tocopherol phosphate as a hydrating agent - Google Patents

Use of tocopherol phosphate as a hydrating agent Download PDF

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Publication number
WO2015092227A1
WO2015092227A1 PCT/FR2014/053276 FR2014053276W WO2015092227A1 WO 2015092227 A1 WO2015092227 A1 WO 2015092227A1 FR 2014053276 W FR2014053276 W FR 2014053276W WO 2015092227 A1 WO2015092227 A1 WO 2015092227A1
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skin
tocopherol phosphate
use according
cells
keratinocytes
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PCT/FR2014/053276
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French (fr)
Inventor
Marc Dumas
Emmanuelle LEBLANC-NOBLESSE
Carine Nizard
Milène JUAN
Clarisse Marteau
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Lvmh Recherche
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Publication of WO2015092227A1 publication Critical patent/WO2015092227A1/en

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    • 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
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • 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
    • A61Q19/007—Preparations for dry skin

Definitions

  • the invention relates to the use of tocopherol phosphate or a salt thereof as a moisturizing agent of the skin.
  • WO 91/11189 describes the use of an alpha-tocopherol phosphate in pharmaceutical, cosmetic or dermatological compositions for the prevention or treatment of the harmful effects of free radicals.
  • WO 2008/001921 discloses anti-wrinkle compositions which comprise the tocopherol phosphate or a salt thereof
  • WO 2003/094882 discloses a whitening or lightening composition of the skin comprising tocopherol in the form of a dispersion or an aqueous solution.
  • tocopherol phosphate or one of its salts has an effect on the expression of type 3 aquaporin in human keratinocytes, especially from cells with high potential for clonogenicity ("stem cells").
  • aquaporins are transmembrane protein systems facilitating the passage of small molecules such as water, glycerol and urea.
  • Aquaporin type 3 (AQP-3) is located in the human epidermis, specifically in the plasma membrane of keratinocytes, in which it plays an important role in the transport and distribution of water, but also glycerol.
  • AQP-3 is thus a major biological marker involved in the mechanisms of cutaneous hydration, both to compensate for the evaporation of epidermal water (insensible loss of water) and to convey and distribute it within the body. 'epidermis.
  • the keratinocytes capable of forming the epidermis there are cells with a high potential for clonogenicity which will produce the largest quantity of daughter cells and thus play a role. essential role in cell renewal at the level of the epidermis and maintain this renewal in the long term.
  • keratinocytes which can be described as “keratinocytes-strains” or “keratinocytes-progenitors", represent less than 1% of the number of cells constituting the epidermis and are preferentially located at the level of the basal layer of the This protects them more effectively against the action of free radicals and damage to DNA, in particular induced by the action of solar radiation, in particular UV-B, which are largely filtered by cell layers. of the epidermis.
  • stem cells are particularly sensitive to osmotic stress induced by dehydration factors, which makes them particularly vulnerable to environmental variations likely to produce such stress and which causes a drastic reduction in their clonogenic potential.
  • the inventors have now shown that it is possible to stimulate the expression of AQP-3 in keratinocytes of the epidermis in a particularly intense manner, and that this stimulating effect is exerted more intensively on keratinocytes with a high potential for clonogenicity, also called “stem cells” or “keratinocytes stem” or “progenitor keratinocytes” in the present application.
  • Tocopherol phosphate is thus a particularly interesting agent for moisturizing the skin or ensuring the maintenance of the hydration of the epidermis, or preventing dehydration, because of its stimulating action of AQP-3 in epidermal keratinocytes. , and more particularly on keratinocytes with high clonogenicity potential and daughter cells present in cell clones they produce.
  • Dry skin has an alteration of lipids on the surface of the skin that induces a change in their skin barrier. Disturbed, the skin barrier is less effective in retaining water, and exposes the cells of the epidermis to dehydration and osmotic stress. Exposure to cold or a drying environment, successive cleanings, and all stresses on the surface of the skin and altering its constituents, such as pollution, solar radiation, and an unbalanced diet lipid precursors, are factors aggravating this loss of fluid balance.
  • the inventors have observed that the growth of normal human keratinocytes cultured in vitro is greatly reduced in the presence of sorbitol, the latter favoring, according to the principles of osmosis, an exit of the water from the cells and thus an osmotic stress. Under these conditions, the inventors observed that the growth of epidermal stem cells was greatly diminished. Thus, the ability of epidermal stem keratinocytes to form new cells and to sustain long-term cellular renewal of the epidermis is significantly more altered over time in dehydration, therefore in dry skin or in the skin. skin whose water barrier is impaired, only in a normal situation.
  • the present invention therefore provides a method of hydration of dry and mature skin, which are particularly exposed to cold, usually in winter or in a desiccating environment due to dry air, or which are subject to regular cleaning actions or removal of makeup, or to domestic or external air pollutants that alter the constituents of the skin surface.
  • tocopherol phosphate makes its use particularly interesting in cosmetic compositions to achieve care where one seeks to maintain or promote the hydration of the skin.
  • the main object of the present invention is therefore to provide a new use of tocopherol phosphate.
  • the present invention also aims to provide a cosmetic care method for moisturizing the skin, especially when the cells of the epidermis are subjected to osmotic stress due to cold or more generally to an external desiccating environment.
  • the present invention is particularly adapted to the care of skin exposed to an urban environment, in particular to the atmospheric pollutants of large cities, these pollutants being capable of altering the water barrier function and thus of causing osmotic stress.
  • the present invention also aims to provide a cosmetic care method for moisturizing delicate skin which have a particular fragility to the use of surfactants and a mechanical action, both types of aggression can be combined during the make-up removal and daily cleaning.
  • the present invention is also particularly suitable for skins which have an aquaporin-3 deficiency, such as dry skin, but also so-called mature skin or skin exposed to the sun, in particular the areas of the face, Vietnameselleté and hands and the skin. body areas where the drought is more intense, for example in the legs and arms but also the lips.
  • an aquaporin-3 deficiency such as dry skin
  • mature skin or skin exposed to the sun in particular the areas of the face, décolleté and hands and the skin. body areas where the drought is more intense, for example in the legs and arms but also the lips.
  • the present invention is particularly useful for skins with high phototypes whose dryness causes the appearance of whitish dander contrasting with the skin color and therefore particularly visible.
  • the present invention may be particularly recommended at times of the day when the insensible loss of water of the skin is greater and therefore requires a compensatory water intake such as late afternoon or midday.
  • the present invention is also suitable for skincare of eczematous nature and especially in cases of spongiosis where it has been shown a significant deficiency of epidermal AQP-3 particularly marked in the lesion areas.
  • the invention relates to the use, in a cosmetic composition, of tocopherol phosphate or of one of its salts, as an agent intended to maintain or restore the hydration state of the skin, said composition also containing a cosmetically excipient acceptable.
  • Figures 1 to 3 given with reference to Example 1, in the form of histograms, the expression of AQP-3 detected by immunolabeling in cutaneous cells in culture exposed to different compounds, including tocopherol.
  • the extract solution of Ajuga turkestanica, known to stimulate AQP3 is used as a positive control.
  • Figure 1 shows the total expression of AQP-3 for colonies of daughter cells derived from keratinocytes having a low potential clonogenicity (small clones), means (means clones) or high (large clones), and exposed to different assets.
  • FIG. 2 shows the expression of AQP-3 in the cell by colony daughter cells from keratinocytes high potential clonogenicity (keratinocyte stem), exposed to different doses of tocopherol phosphate.
  • FIG. 3 represents the expression of AQP-3 per cell in the colonies of daughter cells derived from keratinocytes with a high potential for clonogenicity (keratinocytes-strains) exposed to different active agents and to their mixture.
  • the tocopherol phosphate may be in the form of a base or a cosmetically acceptable salt.
  • a tocopherol phosphate salt an alkali metal salt, and preferably a sodium salt, is preferred.
  • the tocopherol phosphate is alpha-tocopherol, beta-tocopherol, delta-tocopherol or gamma-tocopherol phosphate, and more particularly sodium gamma tocopherol phosphate.
  • the tocopherol phosphate or a salt thereof may thus be used in a cosmetic composition as a cosmetic active agent to obtain an effect of maintaining or reinforcing the hydration of the skin.
  • the present invention thus has for its first object the use, as moisturizing agent of the skin, of tocopherol phosphate or a cosmetically acceptable salt thereof.
  • the cosmetic composition comprises an effective amount of tocopherol phosphate to achieve the desired effect.
  • composition thus preferably comprises from 0.001% to 5%, preferably from 0.01% to 1%, by dry weight of tocopherol phosphate.
  • the active agent may be associated with one or more molecules and / or one or more plant extracts having moisturizing properties, such as glycols, in particular glycerol, or natural polyols, natural or synthetic ceramides, urea, hyaluronic acid, lactic acid, or an extract of Ajuga turkestanica.
  • moisturizing properties such as glycols, in particular glycerol, or natural polyols, natural or synthetic ceramides, urea, hyaluronic acid, lactic acid, or an extract of Ajuga turkestanica.
  • an active agent or active agents which, used alone or in combination, increase the expression of AQP-3 in the cells of the skin, such as an extract Ajuga turkestanica, an extract of Paeonia suffrutica, an extract of roses, Kniphophia uvaria, Heistanus annuus, Oriza sativa, Malva sylvestris, Sanguisorba officinalis, Glycine max, Saccharomyces orevisiae, Onopordum acanthrium, Zea mays, Filipendula ulmaria, Salixalba, Rhodophyccea and ascorbic acid-2-glucoside.
  • an active agent or active agents which, used alone or in combination, increase the expression of AQP-3 in the cells of the skin, such as an extract Ajuga turkestanica, an extract of Paeonia suffrutica, an extract of roses, Kniphophia uvaria, Heistanus annuus, Oriza s
  • the active agent may also be advantageously combined, in cosmetic compositions, with at least one extract of at least one other plant belonging to the orchid family (Orchidaceae).
  • This additional extract of another plant belonging to the family of orchids may be in particular an extract of at least one orchid of the genus Vanda such as orchid Vanda Coerulea which also has an action on the aquaporins of the cells of the epidermis .
  • tocopherol phosphate in particular with extracts of plants known to slow or prevent the appearance of signs of skin dryness by a humectant action, a stimulating action of hyaluronic acid formation or inhibiting its degradation.
  • an action stimulating the formation of tight junctions of the epidermis or "tight junctions" which limit the loss of water intercellular water a stimulating action of the formation of the receptor of hyaluronic acid or CD44, a stimulating action of the formation of the cohesive junctions of the epidermis, desmosomes and corneo-desmosomes, a stimulating action of the formation of epidermal lipids, in particular ceramides, fatty acids and cholesterol, which participate in the function of water barrier, an action stimulating the synthesis of sebum, in particular squalene and triglycerides, or conversely an inhibitory action of 5-alpha-reductase as Linum usitatissimum seed extract, or an occlusive action on the surface of the skin.
  • tocopherol phosphate one or more molecules or plant extracts with antioxidant properties.
  • Such antioxidants may be for example polyphenols, tannic acid, epigallocathechin and natural extracts containing them, epigallocatechin-3-gallate, anthocyanins, carotenes, rosemary extracts, leaf extracts olive oil, green tea, resveratrol and its derivatives, Pycnogenol, ergothioneine, N acetylcysteine, biotin, chelants, idebenone, plant extracts horn Pronalen Bioprotect TM from the company Provital, the co-enzyme Q10, bioflavonoids, SOD, phytantriol, lignans, melatonin, pidolates, tocopherol acetate or palmitate, ascorbic acid and its salts, arginine pyrrolidone carboxylate, selenated derivatives , idebenone, glutathione, and different isoforms of tocotrienol and ergothioneine.
  • the cosmetic composition comprises at least one cosmetically or dermatologically acceptable excipient which may be chosen from pigments, dyes, polymers, surfactants, rheology agents, perfumes, electrolytes, adjusters pH, antioxidants, preservatives, and mixtures thereof.
  • the cosmetic composition may for example be in the form of a serum, a lotion, a cream or a hydrogel, a mask, or be in the form of a stick, or a patch.
  • the extracts and compositions have a particularly desired effect for maintaining or enhancing the hydration state of the skin, when applying said extract or said composition to the skin of the face or body.
  • the present invention relates, as previously discussed, to the use of tocopherol phosphate as a cosmetic agent for maintaining or reinforcing the hydration state of the skin.
  • Tocopherol phosphate advantageously strengthens the ability of skin cells to adapt to osmotic stress and / or promote their clonogenic potential.
  • the active agent used in the context of the invention advantageously makes it possible to restore the hydration state of the keratinocytes of the epidermis. It is particularly interesting to restore the hydration state of a mature and dry skin.
  • “Mature skin” means the skin of a person over 35, over 40, or over 45 years old.
  • the subject of the invention is also a cosmetic care method using the extract defined above or a cosmetic composition as defined above comprising an effective amount of said tocopherol phosphate for maintaining or reinforcing the hydration state of the skin and / or again to obtain an effect of preventing or slowing down the appearance of the signs of cutaneous dryness.
  • the invention also relates to a cosmetic skin care method which comprises the application to at least a part of the face or the body, in particular undergoing osmotic stress, an effective amount of tocopherol phosphate or a of its salts described above, or a composition containing it as defined above.
  • a cosmetic skin care method which comprises the application to at least a part of the face or the body, in particular undergoing osmotic stress, an effective amount of tocopherol phosphate or a of its salts described above, or a composition containing it as defined above.
  • Example 1 Activity tests for tocopherol phosphate as an agent stimulating the expression of Raauaporin-3.
  • the objective of this study was to evaluate the effect of tocopherol phosphate on the expression of aquaporin-3 from normal human keratinocytes (KHN) derived from stem cells in culture. This evaluation was made by immunofluorescent staining after a KHN clonogenicity test. Materials and methods
  • Keratinocytes were cultured according to the simplified method of
  • Green (Rheinwald and Green, 1975) (Rheinwald JG and Green Co., 1975, 6: 331-343), i.e. on a feeder layer of gamma-irradiated human fibroblasts, which does not divide more.
  • the gamma-irradiated fibroblasts were seeded at 8000 cells per cm 2 in Petri dishes and cultured at 37 ° C and 5% CO 2 in complete "Green" medium.
  • the KHNs are seeded on the feeder layer of fibroblasts at a rate of 4000 cells per cm 2 in medium of "Green".
  • the extract û'Ajuga turkestanica (Jistenine ® HG, DIE Latoxan, 5% solution in weight of dry extract, glycerol extract / water) is known to stimulate the AQP-3. It is used as a positive control.
  • the tocopherol phosphate was tested on the cell culture model described in the previous paragraph.
  • the tested active agents were added to the culture medium for a treatment time of 48 h.
  • the cells are rinsed twice with PBS and then fixed with formalin (Formalin 10% Neutral Buffered Solution, Sigma) for 10 minutes.
  • formalin Formin 10% Neutral Buffered Solution, Sigma
  • the cell membranes were permeabilized with 0.1% PBS / Triton solution (Triton X-100, Sigma), and then the cells were rinsed twice with PBS.
  • the cells were then overlaid with 1% PBS / BSA solution (Albumin from bovine serum, Sigma) for 30 minutes and at room temperature.
  • PBS / BSA solution Albumin from bovine serum, Sigma
  • PBS / BSA solution was aspirated and replaced with a solution of primary antibody anti-AQP-3 (goat polyclonal IgG, Santa Cruz Biotechnology) diluted to l / 200th in PBS / BSA.
  • the dishes were placed in a humid chamber for 60 minutes at room temperature.
  • the dishes were rinsed three times with PBS.
  • the cells were then covered with a solution of anti-goat secondary antibody (Alexa Fluor 546 rabbit anti-goat IgG, Invitrogen-Molecular Probes) diluted to l / 200th in PBS / BSA.
  • the dishes are placed in the dark for 60 minutes at room temperature.
  • the boxes were stored at 4 ° C and in the dark.
  • the images were made with a Leica SP5 II confocal microscope with the x10 "dry" objective at 1024 x 1024 pixels. For each condition, the images were made with the same acquisition parameters.
  • the images are analyzed using the Leica QWin image analysis software.
  • the contour of the cell colonies or clones is traced to determine the total area and the marked area after detection of AQP-3 labeling. 4.
  • the significance of the differences in surface ratios observed between the controls and the treatments was measured by the Student's test (correlated with the F test). The Student's test is said to be significant if its value is less than 0.05.
  • the activity is expressed as the amount of AQP3 in each clone, while in Figures 2 and 3 the activity is expressed as the percentage of AQP3 per cell.
  • the clones colonnies
  • the size of the colony depends directly on the potential of clonogenicity of the mother cell.
  • Small clones (0 to 100,000 micron 2 ) are derived from keratinocytes with a low potential for clonogenicity.
  • the medium size clones (100,000 to 200,000 micron 2 ) are derived from keratinocytes with a medium potential for clonogenicity.
  • tocopherol acts more specifically on the cells derived from keratinocytes-strains which form the largest colonies.
  • the tocopherol phosphate exhibits a significant activity on the expression of AQP-3 for cells derived from keratinocytes with a high potential for clonogenicity compared with the expression measured for cells derived from keratinocytes with a lower potential for clonogenicity.
  • a more intense effect is observed on the total expression of AQP-3 in a colony of cells derived from keratinocytes-strains, compared with the effect measured on the colonies derived from cells with medium or low clonogenicity potential ( amplification cells).
  • the effect is lower than for keratinocytes-strains with a high potential for clonogenicity.
  • the effect remains significantly greater than that of the untreated control, which shows an efficacy of phosphate tocopherol phosphate on the expression of AQP-3 on several types of keratinocytes.
  • FIG. 2 A significant dose effect is also observed in FIG. 2: when the concentration of tocopherol phosphate in the medium is increased, the expression of AQP-3 increases significantly.
  • Table 1 shows the average values of the expression of AQP3 per cell derived from a colony produced by a keratinocyte with a high potential for clonogenicity.
  • FIG. 3 shows that the effect obtained on the cells of large clones for tocopherol phosphate is same order of magnitude as that obtained for the positive control, extract 6'Ajuga turkestanica.
  • the combination of the two active agents itself substantially indicates an addition of the stimulating effect on the expression of aquaporin 3, which makes this combination particularly advantageous in cosmetic compositions intended to moisturize the skin, and more particularly the epidermis .
  • Tocopherol phosphate significantly stimulates the expression of aquaporin 3 irrespective of the size of the clones.
  • Tocopherol phosphate has a particularly significant effectiveness in regulating the hydrous and glycerol fluxes in the epidermis, thus allowing better hydration of the basal layers of the epidermis.
  • Ajuga turkestanica extract and tocopherol phosphate is therefore particularly advantageous for stimulating the expression of aquaporin 3 in keratinocyte progenitors with high clonogenic potential (cells derived from stem cells).
  • This combination is therefore particularly recommended for targeting this particular population of epidermal cells, in cosmetic compositions whose application to the skin makes it possible to enhance the ability of these epidermal cells to adapt to osmotic stress and to promote the maintenance of their strong clonogenic potential.
  • tocopherol phosphate with the extract of Ajuga turkestanica, a moisturizing agent known for its action on AQP-3, has an additional beneficial effect on the expression of AQP-3.
  • the effect is specific to clones derived from stem keratinocytes which have a primordial role in the renewal of the epidermis due to this ability to produce clones containing a large amount of cells.
  • the stimulatory effect of AQP-3 thus extends to the largest number of daughter cells. This allows a better resistance to the osmotic stress of these cells and ensures the maintenance of sufficient hydration in the epidermis.
  • Tocopherol phosphate is used as a moisturizing agent in the following cosmetic compositions.
  • aqueous solution comprising the following active ingredients (percentage by weight) is prepared:
  • the lotion is applied daily on the face.
  • a moisturizing emulsion is prepared whose formula is indicated below (% by weight)
  • phase A gelling agents are dispersed in water and then heated to 80-85 ° C, before solubilizing the compounds.
  • the compounds of phase B are heated to 85 ° C to form a homogeneous phase.
  • Phase A is emulsified in phase B using a Ystral mixer.
  • the oil / water emulsion is finally neutralized with an aqueous solution of sodium hydroxide, and then cooled.
  • composition obtained is a moisturizer intended to be applied to the face or part of the face. 3 - Cream for the warmtha
  • a serum is prepared according to the following formula (% by weight):
  • Carbomer (Carbopol® Ultrez 10) 0.5%
  • the phospholipids of the D phase are homogenized with the ultraturrax, with butylene glycol and glycerol for 20 minutes.
  • the other compounds of phase D are added, followed by the purified water.
  • the lamellar phase obtained is sheared for 20 minutes with Ultraturrax to form the liposome dispersion.
  • the tocopherol phosphate in salt form is included in the serum as an active agent and is encapsulated in the liposomes thus prepared.
  • the compounds of phase A are heated to 80 ° C.
  • the compounds of phase B are added, and the gel is allowed to swell before adding the compounds of phase C into the previously formed gel.
  • the liposome dispersion is added to the previously prepared aqueous phase.
  • the serum comprises multilamellar liposomes in which the tocopherol phosphate salt is encapsulated.
  • the serum is applied to the skin of the face and blow, especially on areas showing signs of dehydration or due to exposure to environmental stresses (cold or UV) causing drying of the skin.

Abstract

The invention relates to the use of tocopherol phosphate in a cosmetic composition, as an agent for maintaining or restoring the state of hydration of the skin or preventing the dehydration thereof. This skin-hydrating effect is obtained especially by stimulation of the expression of aquaporin 3. The invention also relates to a method for the cosmetic care of skin in order to improve the state of hydration thereof.

Description

UTILISATION DU PHOSPHATE DE TOCOPHEROL COMME AGENT  USE OF TOCOPHEROL PHOSPHATE AS AGENT
HYDRATANT  HYDRATANT
L'invention concerne l'utilisation du phosphate de tocophérol ou d'un de ses sels comme agent hydratant de la peau. The invention relates to the use of tocopherol phosphate or a salt thereof as a moisturizing agent of the skin.
ETAT DE LA TECHNIQUE STATE OF THE ART
On connaît de longue date l'activité anti-oxydante du phosphate de tocophérol et son utilisation dans des compositions cosmétiques. Par exemple, WO 91/11189 décrit l'utilisation d'un phosphate d'alpha-tocophérol dans des compositions pharmaceutiques, cosmétiques ou dermatologiques pour la prévention ou le traitement des effets nocifs des radicaux libres.  The antioxidant activity of tocopherol phosphate and its use in cosmetic compositions has been known for a long time. For example, WO 91/11189 describes the use of an alpha-tocopherol phosphate in pharmaceutical, cosmetic or dermatological compositions for the prevention or treatment of the harmful effects of free radicals.
Les activités anti-âge et blanchissante de la peau du phosphate de tocophérol ont également été mises en évidence. Ainsi, WO 2008/001921 décrit des compositions anti-rides qui comprennent le phosphate de tocophérol ou un de ses sels, et WO 2003/094882 décrit une composition blanchissante ou éclaircissante de la peau comprenant du tocophérol sous forme de dispersion ou de solution aqueuse.  The anti-aging and whitening activities of the skin of tocopherol phosphate have also been highlighted. Thus, WO 2008/001921 discloses anti-wrinkle compositions which comprise the tocopherol phosphate or a salt thereof, and WO 2003/094882 discloses a whitening or lightening composition of the skin comprising tocopherol in the form of a dispersion or an aqueous solution.
Il a maintenant été découvert de manière totalement inattendue par les inventeurs de la présente invention, que le phosphate de tocophérol ou un de ses sels, présente un effet sur l'expression de l'aquaporine de type 3 dans des kératinocytes humains, issus notamment de cellules à fort potentiel de clonogénicité (« cellules-souches »).  It has now been discovered completely unexpectedly by the inventors of the present invention that the tocopherol phosphate or one of its salts has an effect on the expression of type 3 aquaporin in human keratinocytes, especially from cells with high potential for clonogenicity ("stem cells").
On rappelle que les aquaporines sont des systèmes protéiques transmembranaires facilitant le passage de petites molécules telles que l'eau, le glycérol et l'urée.  It is recalled that aquaporins are transmembrane protein systems facilitating the passage of small molecules such as water, glycerol and urea.
L'aquaporine de type 3 (AQP-3) est localisée dans l'épiderme humain, plus précisément dans la membrane plasmique des kératinocytes, au sein de laquelle elle exerce un rôle important dans le transport et la distribution de l'eau, mais également du glycérol.  Aquaporin type 3 (AQP-3) is located in the human epidermis, specifically in the plasma membrane of keratinocytes, in which it plays an important role in the transport and distribution of water, but also glycerol.
L'AQP-3 est ainsi un marqueur biologique majeur impliqué dans les mécanismes de l'hydratation cutanée, tant pour compenser l'évaporation de l'eau épidermique (perte insensible en eau) que pour acheminer et distribuer celle-ci au sein de l'épiderme. Parmi les kératinocytes capables de former l'épiderme, on distingue des cellules à fort potentiel de clonogénicité qui vont produire la plus grande quantité de cellules-filles et ainsi jouer un rôle primordial dans le renouvellement cellulaire au niveau de l'épiderme et maintenir ce renouvellement sur le long terme. AQP-3 is thus a major biological marker involved in the mechanisms of cutaneous hydration, both to compensate for the evaporation of epidermal water (insensible loss of water) and to convey and distribute it within the body. 'epidermis. Among the keratinocytes capable of forming the epidermis, there are cells with a high potential for clonogenicity which will produce the largest quantity of daughter cells and thus play a role. essential role in cell renewal at the level of the epidermis and maintain this renewal in the long term.
Ces kératinocytes particuliers, qu'on peut qualifier de « kératinocytes-souches » ou encore de « kératinocytes-progéniteurs », ne représentent moins de 1% du nombre de cellules constituant l'épiderme et sont localisés préférentiellement au niveau de la couche basale de celui-ci, ce qui les protège plus efficacement contre l'action des radicaux libres et des dommages à l'ADN, notamment induits par l'action du rayonnement solaire, en particulier les UV-B qui sont en grande partie filtrés par les strates cellulaires supérieures de l'épiderme.  These particular keratinocytes, which can be described as "keratinocytes-strains" or "keratinocytes-progenitors", represent less than 1% of the number of cells constituting the epidermis and are preferentially located at the level of the basal layer of the This protects them more effectively against the action of free radicals and damage to DNA, in particular induced by the action of solar radiation, in particular UV-B, which are largely filtered by cell layers. of the epidermis.
Ces cellules-souches sont particulièrement sensibles au stress osmotique induit par des facteurs de déshydratation, ce qui les rend particulièrement vulnérables aux variations environnementales susceptibles de produire un tel stress et qui provoque une réduction drastique de leur potentiel clonogénique.  These stem cells are particularly sensitive to osmotic stress induced by dehydration factors, which makes them particularly vulnerable to environmental variations likely to produce such stress and which causes a drastic reduction in their clonogenic potential.
Compte tenu du faible nombre de ces kératinocytes-souches et de leur haute sensibilité à une situation de déshydratation, il est particulièrement important que ces cellules soient en mesure de produire les protéines assurant leur hydratation optimale, notamment pour répondre à l'application d'un stress osmotique.  Given the small number of these keratinocytes strains and their high sensitivity to a dehydration situation, it is particularly important that these cells are able to produce the proteins ensuring their optimal hydration, especially to meet the application of a osmotic stress.
Les inventeurs ont à présent montré qu'il est possible de stimuler de façon particulièrement intense l'expression de l'AQP-3 au niveau des kératinocytes de l'épiderme, et que cet effet de stimulation s'exerce de façon plus intense sur des kératinocytes à fort potentiel de clonogénicité, encore appelés « cellules souches » ou « kératinocytes souches » ou « kératinocytes progéniteurs » dans la présente demande.  The inventors have now shown that it is possible to stimulate the expression of AQP-3 in keratinocytes of the epidermis in a particularly intense manner, and that this stimulating effect is exerted more intensively on keratinocytes with a high potential for clonogenicity, also called "stem cells" or "keratinocytes stem" or "progenitor keratinocytes" in the present application.
Sous l'action du phosphate de tocophérol, on observe ainsi une augmentation significative de la production d'AQP-3 au niveau des clones de cellules issus des kératinocytes souches. A titre de comparaison, les cellules des clones issues de cellules n'ayant pas ce fort potentiel de clonogénicité présentent elles aussi une stimulation de l'expression de l'AQP-3, mais dans une moindre mesure.  Under the action of tocopherol phosphate, there is thus a significant increase in the production of AQP-3 at the level of stem cell clones derived from stem keratinocytes. By way of comparison, the cells of the clones originating from cells which do not have this high potential for clonogenicity also show a stimulation of the expression of AQP-3, but to a lesser extent.
Le phosphate de tocophérol est ainsi un agent particulièrement intéressant pour hydrater la peau ou assurer le maintien de l'hydratation de l'épiderme, ou prévenir de sa deshydratation, du fait de son action stimulante de l'AQP-3 au niveau des kératinocytes épidermiques, et plus particulièrement sur les kératinocytes à fort potentiel de clonogénicité et les cellules filles présentes dans les clones de cellules qu'ils produisent. Tocopherol phosphate is thus a particularly interesting agent for moisturizing the skin or ensuring the maintenance of the hydration of the epidermis, or preventing dehydration, because of its stimulating action of AQP-3 in epidermal keratinocytes. , and more particularly on keratinocytes with high clonogenicity potential and daughter cells present in cell clones they produce.
Les peaux sèches présentent une altération des lipides de la surface de la peau qui induit une modification de leur barrière cutanée. Perturbée, la barrière cutanée est moins efficace pour retenir l'eau, et expose les cellules de l'épiderme à une déshydratation et un stress osmotique . L'exposition au froid ou a une environnement desséchant, les nettoyages successifs, et tous les stress agressant la surface de la peau et altérant ses constituants, comme la pollution, le rayonnement solaire, et un régime alimentaire déséquilibré en précurseurs lipidiques, sont des facteurs aggravant cette perte d'équilibre hydrique.  Dry skin has an alteration of lipids on the surface of the skin that induces a change in their skin barrier. Disturbed, the skin barrier is less effective in retaining water, and exposes the cells of the epidermis to dehydration and osmotic stress. Exposure to cold or a drying environment, successive cleanings, and all stresses on the surface of the skin and altering its constituents, such as pollution, solar radiation, and an unbalanced diet lipid precursors, are factors aggravating this loss of fluid balance.
Les inventeurs ont observé que la croissance de kératinocytes humain normaux cultivés in vitro est fortement diminuée en présence de sorbitol, ce dernier favorisant, selon les principes de l'osmose une sortie de l'eau des cellules et donc un stress osmotique. Dans ces conditions, les inventeurs ont observé que la croissance des cellules souches épidermiques était fortement diminuée. Ainsi, la capacité des kératinocytes souches de l'épiderme à former de nouvelles cellules et à soutenir sur le long terme le renouvellement cellulaire de l'épiderme est nettement plus altéré au cours du temps en situation de déshydratation donc dans les peaux sèches ou dans les peau dont la barrière hydrique est altérée, que dans une situation normale.  The inventors have observed that the growth of normal human keratinocytes cultured in vitro is greatly reduced in the presence of sorbitol, the latter favoring, according to the principles of osmosis, an exit of the water from the cells and thus an osmotic stress. Under these conditions, the inventors observed that the growth of epidermal stem cells was greatly diminished. Thus, the ability of epidermal stem keratinocytes to form new cells and to sustain long-term cellular renewal of the epidermis is significantly more altered over time in dehydration, therefore in dry skin or in the skin. skin whose water barrier is impaired, only in a normal situation.
La présente invention propose donc une méthode d'hydratation des peaux sèches et matures, qui sont notamment exposées au froid, généralement en période hivernale ou dans un environnement desséchant dû à un air sec, ou encore , qui sont soumises à des actions régulières de nettoyage ou de démaquillage, ou encore à des polluants atmosphériques domestiques ou extérieurs qui altèrent les constituants de la surface cutanée.  The present invention therefore provides a method of hydration of dry and mature skin, which are particularly exposed to cold, usually in winter or in a desiccating environment due to dry air, or which are subject to regular cleaning actions or removal of makeup, or to domestic or external air pollutants that alter the constituents of the skin surface.
La découverte de nouvelles propriétés du phosphate de tocophérol rend son utilisation particulièrement intéressante dans des compositions cosmétiques pour réaliser des soins où l'on cherche à maintenir ou à favoriser l'hydratation de la peau.  The discovery of new properties of tocopherol phosphate makes its use particularly interesting in cosmetic compositions to achieve care where one seeks to maintain or promote the hydration of the skin.
La mise en évidence de l'activité hydratante du phosphate de tocophérol est particulièrement inattendue et intéressante car Texpression de l'AQP-3 dans les cellules cutanées diminue avec l'âge ainsi qu'avec l'exposition au rayonnement solaire. Enfin il a été mis en évidence qu'un stress osmotique appliqué sur des kératinocytes capables de se régénérer intensifiait le niveau d'oxydation intracellulaire. Ainsi, cette relation entre le processus oxydatif participant au vieillissement des cellules de la peau, et le degré d'hydratation de la peau suggère qu'une meilleure hydratation des couches superficielles de la peau apportée par le phosphate de tocophérol permet de limiter l'excès d'oxydation de la peau mais aussi d'améliorer l'efficacité des molécules anti-oxydantes endogènes ou d'agents cosmétiques présentant un tel effet antioxydant. BUTS DE L'INVENTION The highlighting of the moisturizing activity of tocopherol phosphate is particularly unexpected and interesting because the expression of AQP-3 in cutaneous cells decreases with age as well as with exposure to solar radiation. Finally, it has been demonstrated that osmotic stress applied to regenerating keratinocytes intensifies the level of intracellular oxidation. Thus, this relationship between the oxidative process involved in the aging of the skin cells and the degree of hydration of the skin suggests that a better hydration of the superficial layers of the skin provided by the tocopherol phosphate makes it possible to limit the excess oxidation of the skin but also to improve the effectiveness of endogenous antioxidant molecules or cosmetic agents having such an antioxidant effect. GOALS OF THE INVENTION
La présente invention a ainsi pour but principal de fournir une nouvelle utilisation du phosphate de tocophérol.  The main object of the present invention is therefore to provide a new use of tocopherol phosphate.
La présente invention a encore pour but de fournir une méthode de soin cosmétique destinée à hydrater la peau, en particulier lorsque les cellules de l'épiderme sont soumises à un stress osmotique dû au froid ou plus généralement à un environnement externe desséchant.  The present invention also aims to provide a cosmetic care method for moisturizing the skin, especially when the cells of the epidermis are subjected to osmotic stress due to cold or more generally to an external desiccating environment.
La présente invention est particulièrement adaptée au soin des peaux exposées à un environnement urbain, en particulier aux polluants atmosphériques des grandes villes, ces polluants étant capables d'altérer la fonction de barrière à l'eau et donc de provoquer un stress osmotique.  The present invention is particularly adapted to the care of skin exposed to an urban environment, in particular to the atmospheric pollutants of large cities, these pollutants being capable of altering the water barrier function and thus of causing osmotic stress.
La présente invention a aussi pour but de fournir une méthode de soin cosmétique destinée à hydrater les peaux délicates qui présentent une fragilité particulière à l'utilisation de tensioactifs et à une action mécanique, ces deux types d'agressions pouvant être combinées lors du démaquillage et du nettoyage quotidien.  The present invention also aims to provide a cosmetic care method for moisturizing delicate skin which have a particular fragility to the use of surfactants and a mechanical action, both types of aggression can be combined during the make-up removal and daily cleaning.
La présente invention est également particulièrement adaptée aux peaux qui présentent un déficit en aquaporine-3 comme les peaux sèches, mais également les peaux dites matures ou encore les peaux exposées au soleil, en particulier les zones du visage, du décolleté et des mains et les zones corporelles où la sécheresse est plus intense, par exemple au niveau des jambes et des bras mais aussi des lèvres.  The present invention is also particularly suitable for skins which have an aquaporin-3 deficiency, such as dry skin, but also so-called mature skin or skin exposed to the sun, in particular the areas of the face, décolleté and hands and the skin. body areas where the drought is more intense, for example in the legs and arms but also the lips.
La présente invention est particulièrement utile pour les peaux à phototypes élevés dont la sécheresse provoque l'apparition de squames blanchâtres contrastant avec la couleur de la peau et donc particulièrement visibles. La présente invention peut être particulièrement recommandée à des moments de la journée où la perte insensible en eau de la peau est plus importante et nécessite donc un apport compensatoire d'eau comme par exemple en fin de journée ou en milieu de journée. The present invention is particularly useful for skins with high phototypes whose dryness causes the appearance of whitish dander contrasting with the skin color and therefore particularly visible. The present invention may be particularly recommended at times of the day when the insensible loss of water of the skin is greater and therefore requires a compensatory water intake such as late afternoon or midday.
La présente invention est aussi adaptée au soin des peaux de natures eczémateuses et tout particulièrement dans les cas de spongiose où il a été montré un déficit important en AQP-3 épidermique particulièrement marquée dans les zones lésionnelles. RESUME DE L'INVENTION  The present invention is also suitable for skincare of eczematous nature and especially in cases of spongiosis where it has been shown a significant deficiency of epidermal AQP-3 particularly marked in the lesion areas. SUMMARY OF THE INVENTION
L'invention concerne l'utilisation, dans une composition cosmétique, du phosphate de tocophérol ou d'un de ses sels, comme agent destiné à maintenir ou restaurer l'état d'hydratation de la peau, ladite composition contenant en outre un excipient cosmétiquement acceptable.  The invention relates to the use, in a cosmetic composition, of tocopherol phosphate or of one of its salts, as an agent intended to maintain or restore the hydration state of the skin, said composition also containing a cosmetically excipient acceptable.
DESCRIPTION DES FIGURES DESCRIPTION OF THE FIGURES
Les Figures 1 à 3, données en référence à l'exemple 1 présentent sous forme d'histogrammes, l'expression de l'AQP-3 détectée par immuno- marquage dans des cellules cutanées en culture exposées à différents composés, dont le phosphate de tocophérol. La solution d'extrait d'Ajuga turkestanica, connue pour stimuler l'AQP3 est utilisée comme témoin positif. Figures 1 to 3, given with reference to Example 1, in the form of histograms, the expression of AQP-3 detected by immunolabeling in cutaneous cells in culture exposed to different compounds, including tocopherol. The extract solution of Ajuga turkestanica, known to stimulate AQP3 is used as a positive control.
■ La Figure 1 représente l'expression totale de l'AQP-3 pour des colonies de cellules-filles issues des kératinocytes ayant un potentiel de clonogénicité faible (petit clones), moyen (clones moyens) ou élevé (gros clones), et exposées à différents actifs. ■ Figure 1 shows the total expression of AQP-3 for colonies of daughter cells derived from keratinocytes having a low potential clonogenicity (small clones), means (means clones) or high (large clones), and exposed to different assets.
■ La Figure 2 représente l'expression de l'AQP-3 par cellule dans les colonies de cellules-filles issues de kératinocytes à fort potentiel de clonogénicité (kératinocytes-souches), exposées à différentes doses de phosphate de tocophérol. ■ Figure 2 shows the expression of AQP-3 in the cell by colony daughter cells from keratinocytes high potential clonogenicity (keratinocyte stem), exposed to different doses of tocopherol phosphate.
- La Figure 3 représente l'expression de l'AQP-3 par cellule dans les colonies de cellules-filles issues de kératinocytes à fort potentiel de clonogénicité (kératinocytes-souches), exposées à différents actifs et à leur mélange. FIG. 3 represents the expression of AQP-3 per cell in the colonies of daughter cells derived from keratinocytes with a high potential for clonogenicity (keratinocytes-strains) exposed to different active agents and to their mixture.
DESCRIPTION DE L'INVENTION DESCRIPTION OF THE INVENTION
Le phosphate de tocophérol peut être sous la forme d'une base ou bien d'un sel cosmétiquement acceptable. Dans le cas d'un sel de phosphate de tocopherol, on préfère un sel de métal alcalin, et de préférence un sel de sodium. The tocopherol phosphate may be in the form of a base or a cosmetically acceptable salt. In the case of a tocopherol phosphate salt, an alkali metal salt, and preferably a sodium salt, is preferred.
Avantageusement, le phosphate de tocophérol est l'alpha- tocophérol, le béta-tocophérol, le delta-tocophérol ou le gamma-tocophérol phosphate, et plus particulièrement le phosphate de gamma tocophérol de sodium.  Advantageously, the tocopherol phosphate is alpha-tocopherol, beta-tocopherol, delta-tocopherol or gamma-tocopherol phosphate, and more particularly sodium gamma tocopherol phosphate.
Le phosphate de tocophérol ou un de ses sels peut ainsi être utilisé dans une composition cosmétique en tant qu'agent actif cosmétique pour obtenir un effet de maintien ou de renforcement de l'hydratation de la peau.  The tocopherol phosphate or a salt thereof may thus be used in a cosmetic composition as a cosmetic active agent to obtain an effect of maintaining or reinforcing the hydration of the skin.
DESCRIPTION DETAILLEE DE L'INVENTION DETAILED DESCRIPTION OF THE INVENTION
La présente invention a ainsi pour premier objet l'utilisation, comme agent hydratant de la peau, du phosphate de tocophérol ou d'un de ses sels cosmétiquement acceptable.  The present invention thus has for its first object the use, as moisturizing agent of the skin, of tocopherol phosphate or a cosmetically acceptable salt thereof.
La composition cosmétique comprend une quantité efficace de phosphate de tocophérol pour obtenir l'effet recherché.  The cosmetic composition comprises an effective amount of tocopherol phosphate to achieve the desired effect.
La composition comprend ainsi préférentiellement de 0,001% à 5%, de préférence de 0,01% à 1%, en poids sec de phosphate de tocophérol.  The composition thus preferably comprises from 0.001% to 5%, preferably from 0.01% to 1%, by dry weight of tocopherol phosphate.
Les essais réalisés par les inventeurs ont montré que les propriétés hydratantes du phosphate de tocophérol peuvent être également obtenues ou améliorées dans des compositions cosmétiques ou dermatologiques, dans lesquelles l'agent actif est associé avec d'autres agents actifs présentant des effets cosmétiques similaires et/ou complémentaires du phosphate de tocophérol.  The tests carried out by the inventors have shown that the moisturizing properties of the tocopherol phosphate can also be obtained or improved in cosmetic or dermatological compositions, in which the active agent is combined with other active agents having similar cosmetic effects and / or complementary to tocopherol phosphate.
Ainsi, l'agent actif peut être associé à une ou plusieurs molécules et/ou un ou plusieurs extraits végétaux présentant des propriétés hydratantes, tels que les glycols, en particulier le glycérol, ou des polyols naturels, des céramides naturels ou de synthèse, l'urée, l'acide hyaluronique, l'acide lactique, ou encore un extrait ô'Ajuga turkestanica.  Thus, the active agent may be associated with one or more molecules and / or one or more plant extracts having moisturizing properties, such as glycols, in particular glycerol, or natural polyols, natural or synthetic ceramides, urea, hyaluronic acid, lactic acid, or an extract of Ajuga turkestanica.
II est particulièrement intéressant d'associer au phosphate de tocophérol un agent actif ou des agents actifs qui, utilisés seuls ou en en combinaisons, augmentent l'expression de l'AQP-3 au niveau des cellules de la peau, tel qu'un extrait û'Ajuga turkestanica, un extrait de Paeonia suffrutica, un extrait de roses, de kniphophia uvaria, à'He/ianthus annuus, û'Oriza sativa, de Malva sylvestris, de Sanguisorba officinalis, de Glycine max, de Saccharomyces œrevisiae, ù'Onopordum acanthrium, de Zea mays, de Filipendula ulmaria, de Salixalba, de Rhodophyccea et d'acide ascorbique-2-glucoside. It is particularly advantageous to associate with the tocopherol phosphate an active agent or active agents which, used alone or in combination, increase the expression of AQP-3 in the cells of the skin, such as an extract Ajuga turkestanica, an extract of Paeonia suffrutica, an extract of roses, Kniphophia uvaria, Heistanus annuus, Oriza sativa, Malva sylvestris, Sanguisorba officinalis, Glycine max, Saccharomyces orevisiae, Onopordum acanthrium, Zea mays, Filipendula ulmaria, Salixalba, Rhodophyccea and ascorbic acid-2-glucoside.
L'agent actif peut également être avantageusement associé, dans des compositions cosmétiques, avec au moins un extrait d'au moins une autre plante appartenant à la famille des orchidées {Orchidaceaé). Cet extrait supplémentaire d'une autre plante appartenant à la famille des orchidées pourra être en particulier un extrait d'au moins une orchidée du genre Vanda tel que l'orchidée Vanda Coerulea qui présente également une action sur les aquaporines des cellules de l'épiderme.  The active agent may also be advantageously combined, in cosmetic compositions, with at least one extract of at least one other plant belonging to the orchid family (Orchidaceae). This additional extract of another plant belonging to the family of orchids may be in particular an extract of at least one orchid of the genus Vanda such as orchid Vanda Coerulea which also has an action on the aquaporins of the cells of the epidermis .
On pourra aussi choisir d'associer le phosphate de tocophérol en particulier à des extraits de plantes connus pour ralentir ou prévenir l'apparition des signes de sécheresse cutanée par une action humectante, une action stimulante de la formation d'acide hyaluronique ou inhibant sa dégradation, une action stimulant la formation des jonctions serrées de l'épiderme ou « tight junctions » qui limitent la perte d'eau l'eau intercellulaire, une action stimulante de la formation du récepteur de l'acide hyaluronique ou CD44, une action stimulante de la formation des jonction cohésives de l'épiderme, desmosomes et cornéo-desmosomes, une action stimulante de la formation des lipides épidermiques en particulier des céramides, des acides gras et du cholestérol qui participent à la fonction de barrière à l'eau, une action stimulante de la synthèse du sébum en particulier de squalène et des triglycérides, ou à l'inverse une action inhibitrice de la 5-alpha-réductase comme l'extrait de graines de Linum usitatissimum, ou encore une action occlusive à la surface de la peau.  It may also be chosen to associate the tocopherol phosphate in particular with extracts of plants known to slow or prevent the appearance of signs of skin dryness by a humectant action, a stimulating action of hyaluronic acid formation or inhibiting its degradation. , an action stimulating the formation of tight junctions of the epidermis or "tight junctions" which limit the loss of water intercellular water, a stimulating action of the formation of the receptor of hyaluronic acid or CD44, a stimulating action of the formation of the cohesive junctions of the epidermis, desmosomes and corneo-desmosomes, a stimulating action of the formation of epidermal lipids, in particular ceramides, fatty acids and cholesterol, which participate in the function of water barrier, an action stimulating the synthesis of sebum, in particular squalene and triglycerides, or conversely an inhibitory action of 5-alpha-reductase as Linum usitatissimum seed extract, or an occlusive action on the surface of the skin.
Il peut être également particulièrement intéressant d'associer au phosphate de tocophérol, une ou plusieurs molécules ou extraits de plantes présentant des propriétés anti-oxydantes.  It may also be particularly advantageous to associate with the tocopherol phosphate, one or more molecules or plant extracts with antioxidant properties.
De tels anti-oxydants peuvent être par exemple les polyphénols, l'acide tannique, l'épigallocathéchine et les extraits naturels en contenant, l'épigallocatéchine-3-gallate, les anthocyanes, les carotènes, les extraits de romarin, les extraits de feuilles d'olivier, le thé vert, le resvératrol et ses dérivés, le Pycnogénol, l'ergothionéine, la N acétylcystéine, la biotine, les chélatants, l'idébénone, des extraits végétaux corne le Pronalen Bioprotect TM de la société Provital, , le co-enzyme Q10, les bioflavonoides, les SOD, le phytantriol, les lignanes, la mélatonine, les pidolates, l'acétate ou le palmitate de tocophérol, l'acide ascorbique et ses sels, le pyrrolidone carboxylate d'arginine, les dérivés séléniés, l'idébénone, le gluthation, et les différentes isoformes de tocotriénol et l'ergothioneine. Such antioxidants may be for example polyphenols, tannic acid, epigallocathechin and natural extracts containing them, epigallocatechin-3-gallate, anthocyanins, carotenes, rosemary extracts, leaf extracts olive oil, green tea, resveratrol and its derivatives, Pycnogenol, ergothioneine, N acetylcysteine, biotin, chelants, idebenone, plant extracts horn Pronalen Bioprotect TM from the company Provital, the co-enzyme Q10, bioflavonoids, SOD, phytantriol, lignans, melatonin, pidolates, tocopherol acetate or palmitate, ascorbic acid and its salts, arginine pyrrolidone carboxylate, selenated derivatives , idebenone, glutathione, and different isoforms of tocotrienol and ergothioneine.
Outre l'extrait défini précédemment, la composition cosmétique comprend au moins un excipient cosmétiquement ou dermatologiquement acceptable qui peut être choisi parmi des pigments, des colorants, des polymères, des agents tensioactifs, des agents de rhéologie, des parfums, des électrolytes, des ajusteurs de pH, des agents anti-oxydants, des conservateurs, et leurs mélanges.  In addition to the extract defined above, the cosmetic composition comprises at least one cosmetically or dermatologically acceptable excipient which may be chosen from pigments, dyes, polymers, surfactants, rheology agents, perfumes, electrolytes, adjusters pH, antioxidants, preservatives, and mixtures thereof.
La composition cosmétique peut être par exemple sous la forme d'un sérum, d'une lotion, d'une crème ou bien encore d'un hydrogel, d'un masque, ou se présenter sous la forme d'un stick, ou encore d'un patch.  The cosmetic composition may for example be in the form of a serum, a lotion, a cream or a hydrogel, a mask, or be in the form of a stick, or a patch.
Les extraits et les compositions présentent un effet particulièrement recherché pour maintenir ou renforcer l'état d'hydratation de la peau, lorsqu'on applique ledit extrait ou ladite composition sur la peau du visage ou du corps.  The extracts and compositions have a particularly desired effect for maintaining or enhancing the hydration state of the skin, when applying said extract or said composition to the skin of the face or body.
La présente invention concerne, comme exposé précédemment, une utilisation du phosphate de tocophérol en tant qu'agent cosmétique destiné à maintenir ou renforcer l'état d'hydratation de la peau. Le phosphate de tocophérol renforce avantageusement la capacité d'adaptation des cellules de la peau à un stress osmotique et/ou favorise leur potentiel clonogénique. L'agent actif utilisé dans le cadre de l'invention permet avantageusement restaurer l'état d'hydratation des kératinocytes de l'épiderme. Il est particulièrement intéressant pour restaurer l'état d'hydratation d'une peau mature et sèche. Par « peau mature », on entend la peau d'une personne ayant plus de 35 ans, plus de 40 ans, voir plus de 45 ans.  The present invention relates, as previously discussed, to the use of tocopherol phosphate as a cosmetic agent for maintaining or reinforcing the hydration state of the skin. Tocopherol phosphate advantageously strengthens the ability of skin cells to adapt to osmotic stress and / or promote their clonogenic potential. The active agent used in the context of the invention advantageously makes it possible to restore the hydration state of the keratinocytes of the epidermis. It is particularly interesting to restore the hydration state of a mature and dry skin. "Mature skin" means the skin of a person over 35, over 40, or over 45 years old.
L'invention a également pour objet une méthode de soin cosmétique utilisant l'extrait défini précédemment ou une composition cosmétique telle que définie précédemment comprenant une quantité efficace dudit phosphate de tocophérol pour maintenir ou renforcer l'état d'hydratation de la peau et/ou encore pour obtenir un effet de prévention ou de ralentissement de l'apparition des signes de sécheresse cutanée.  The subject of the invention is also a cosmetic care method using the extract defined above or a cosmetic composition as defined above comprising an effective amount of said tocopherol phosphate for maintaining or reinforcing the hydration state of the skin and / or again to obtain an effect of preventing or slowing down the appearance of the signs of cutaneous dryness.
L'invention a également pour objet une méthode de soin cosmétique de la peau qui comprend l'application sur au moins une partie du visage ou du corps, subissant notamment un stress osmotique, d'une quantité efficace de phosphate de tocophérol ou d'un de ses sels décrits précédemment, ou encore d'une composition en contenant telle que précédemment définie. Les caractéristiques qui ont été décrites en rapport avec le premier objet de l'invention relatif à l'utilisation du phosphate de tocophérol comme agent hydratant, s'appliquent aux caractéristiques de la méthode de l'invention, qui constitue un deuxième objet de l'invention. The invention also relates to a cosmetic skin care method which comprises the application to at least a part of the face or the body, in particular undergoing osmotic stress, an effective amount of tocopherol phosphate or a of its salts described above, or a composition containing it as defined above. The characteristics which have been described in relation to the first subject of the invention relating to the use of tocopherol phosphate as a moisturizing agent, apply to the characteristics of the method of the invention, which constitutes a second object of the invention. invention.
Comme cela ressort clairement des exemples ci-après, la demanderesse a mis en évidence l'intérêt du phosphate de tocophérol pour stimuler l'expression de l'AQP-3. As is clear from the examples below, the applicant has shown the interest of tocopherol phosphate to stimulate the expression of AQP-3.
Dans les exemples, tous les pourcentages sont donnés en poids, la température est en degrés Celsius, la pression est la pression atmosphérique, sauf indication contraire.  In the examples, all the percentages are given by weight, the temperature is in degrees Celsius, the pressure is the atmospheric pressure, unless otherwise indicated.
D'autres buts, caractéristiques et avantages de l'invention apparaîtront clairement à la lumière de la description explicative qui va suivre faite en référence à des exemples de tests mettant en évidence les propriétés susmentionnées pour le phosphate de tocophérol et des exemples de composition cosmétique utilisant cet agent, donnés simplement à titre d'illustration et qui ne sauraient donc en aucune façon limiter la portée de l'invention. Exemple 1: Tests d'activité du phosphate de tocophérol en tant qu'agent stimulant l'expression de raauaporine-3.  Other objects, features and advantages of the invention will become clear in the light of the explanatory description which follows, with reference to examples of tests demonstrating the above-mentioned properties for tocopherol phosphate and examples of cosmetic compositions using this agent, given merely by way of illustration and which can not in any way limit the scope of the invention. Example 1: Activity tests for tocopherol phosphate as an agent stimulating the expression of Raauaporin-3.
L'étude a été réalisée à partir de clones de kératinocytes selon la méthode développée par Barrandon et Green {Rarrandon Y and Green H. ; Proc Natl Acad Se/ USA 1987, 84 : 2302-2306) qui permet d'analyser et de distinguer des kératinocytes possédant des fortes capacités à former des clones (également dénommés « kératinocytes-souches » ou « cellules- souches » ou « progéniteurs »), ou des capacités intermédiaires ou faibles (cellules filles dites d'amplification). The study was carried out from keratinocyte clones according to the method developed by Barrandon and Green (Rarrandon Y and Green H.; Proc Natl Acad Se / USA 1987, 84: 2302-2306) which makes it possible to analyze and distinguish keratinocytes having high capacity to form clones (also called "keratinocytes-strains" or "stem-cells" or "progenitors" ), or intermediate or weak capacities (so-called amplification daughter cells).
L'objectif de cette étude était d'évaluer l'effet du phosphate de tocophérol sur l'expression de l'aquaporine-3 de Kératinocytes Humains Normaux (KHN) issus de cellules souches en culture. Cette évaluation a été faite par un marquage immunofluorescent à l'issue d'un test de clonogénicité des KHN. Matériels et méthodes The objective of this study was to evaluate the effect of tocopherol phosphate on the expression of aquaporin-3 from normal human keratinocytes (KHN) derived from stem cells in culture. This evaluation was made by immunofluorescent staining after a KHN clonogenicity test. Materials and methods
1. Préparation des cellules et marquage immunofluorescent 1. Cell preparation and immunofluorescent staining
1.1 Culture cellulaire 1.1 Cell culture
Les kératinocytes ont été cultivés selon la méthode simplifiée de Keratinocytes were cultured according to the simplified method of
«Green» (Rheinwald et Green, 1975) (Rheinwald J.G and GreenH. ; Ce// 1975, 6 : 331-343), c'est-à-dire sur une couche nourricière de fibroblastes humains gamma-irradiés, qui ne se divisent plus. "Green" (Rheinwald and Green, 1975) (Rheinwald JG and Green Co., 1975, 6: 331-343), i.e. on a feeder layer of gamma-irradiated human fibroblasts, which does not divide more.
Après trypsination, les fibroblastes gamma-irradiés ont été ensemencés à raison de 8000 cellules par cm2 dans des boîtes de Pétri et cultivés à 37°C et 5 % de C02 dans du milieu de « Green » complet. After trypsinization, the gamma-irradiated fibroblasts were seeded at 8000 cells per cm 2 in Petri dishes and cultured at 37 ° C and 5% CO 2 in complete "Green" medium.
Après 24 heures de culture, les KHN sont ensemencés sur la couche nourricière de fibroblastes à raison de 4000 cellules par cm2 en milieu de « Green ». After 24 hours of culture, the KHNs are seeded on the feeder layer of fibroblasts at a rate of 4000 cells per cm 2 in medium of "Green".
1.2 Traitements 1.2 Treatments
L'extrait û'Ajuga turkestanica (Jistenine® HG, Latoxan DIE, solution à 5% en poids d'extrait sec, extrait glycérol/eau) est connu pour stimuler l'AQP-3. Il est utilisé comme témoin positif. The extract û'Ajuga turkestanica (Jistenine ® HG, DIE Latoxan, 5% solution in weight of dry extract, glycerol extract / water) is known to stimulate the AQP-3. It is used as a positive control.
On a testé le phosphate de tocophérol sur le modèle de culture cellulaire décrit au paragraphe précédent.  The tocopherol phosphate was tested on the cell culture model described in the previous paragraph.
Après 72 h de culture et la formation de petits clones, les actifs testés, préalablement filtrés, ont été ajoutés au milieu de culture pour un temps de traitement de 48 h.  After 72 h of culture and the formation of small clones, the tested active agents, previously filtered, were added to the culture medium for a treatment time of 48 h.
Solutions d'actifs testés Asset Solutions tested
Témoin non traité (Milieu de Green)  Untreated control (Middle of Green)
Extrait d'Ajuga turkestanica (Jistenine®) à 0,01 % de la solution Ajuga turkestanica extract (Jistenine ® ) 0.01% solution
commerciale dans le milieu de culture  commercial in the culture medium
Phosphate de tocophérol (PVE) à 0,01 % dans le milieu de culture  Tocopherol phosphate (PVE) at 0.01% in the culture medium
Phosphate de tocophérol (PVE) à 0,02 % dans le milieu de culture  Tocopherol phosphate (PVE) at 0.02% in the culture medium
Association Extrait d'Ajuga turkestanica (Jistenine®) à 0,01 % de la Association Ajuga extract turkestanica (Jistenine ® ) 0.01% of the
solution commerciale et du phosphate de tocophérol (PVE) à 0,01 % dans le milieu de culture 1.3 Marquage immunofluorescent commercial solution and 0.01% tocopherol phosphate (PVE) in the culture medium 1.3 Immunofluorescent labeling
Les cellules sont rincées deux fois au PBS puis fixées à la formaline (Formalin Solution 10% Neutral Buffered, Sigma) pendant 10 minutes.  The cells are rinsed twice with PBS and then fixed with formalin (Formalin 10% Neutral Buffered Solution, Sigma) for 10 minutes.
Après deux rinçages au PBS, les membranes des cellules ont été perméabilisées avec une solution de PBS/Triton 0,1% (Triton X-100, Sigma), puis les cellules ont été rincées deux fois au PBS.  After two PBS rinses, the cell membranes were permeabilized with 0.1% PBS / Triton solution (Triton X-100, Sigma), and then the cells were rinsed twice with PBS.
Les cellules ont ensuite été recouvertes d'une solution de PBS/BSA 1% (Albumin from bovine sérum, Sigma), pendant 30 minutes et à température ambiante.  The cells were then overlaid with 1% PBS / BSA solution (Albumin from bovine serum, Sigma) for 30 minutes and at room temperature.
La solution de PBS/BSA a été aspirée et remplacée par une solution d'anticorps primaire anti-AQP-3 (goat polyclonal IgG, Santa Cruz Biotechnology) dilué au l/200eme dans le PBS/BSA. Les boîtes ont été placées dans une chambre humide pendant 60 minutes à température ambiante. Of the PBS / BSA solution was aspirated and replaced with a solution of primary antibody anti-AQP-3 (goat polyclonal IgG, Santa Cruz Biotechnology) diluted to l / 200th in PBS / BSA. The dishes were placed in a humid chamber for 60 minutes at room temperature.
Les boîtes ont été rincées trois fois au PBS. Les cellules ont ensuite été recouvertes d'une solution d'anticorps secondaire anti-goat (Alexa fluor 546, rabbit anti-goat IgG, Invitrogen-Molecular Probes) dilué au l/200eme dans le PBS/BSA. Les boîtes sont placées à l'obscurité pendant 60 minutes à température ambiante. The dishes were rinsed three times with PBS. The cells were then covered with a solution of anti-goat secondary antibody (Alexa Fluor 546 rabbit anti-goat IgG, Invitrogen-Molecular Probes) diluted to l / 200th in PBS / BSA. The dishes are placed in the dark for 60 minutes at room temperature.
Après trois rinçages au PBS et deux à l'eau distillée, quelques gouttes de milieu de montage (Aqueous Mount, ScyTek laboratories) ont été déposées sur la surface de culture des boîtes.  After three rinses with PBS and two with distilled water, a few drops of mounting medium (Aqueous Mount, ScyTek laboratories) were deposited on the culture surface of the dishes.
Les boîtes ont été conservées à 4°C et à l'obscurité.  The boxes were stored at 4 ° C and in the dark.
2. Acquisition des photos 2. Acquisition of photos
Les images ont été réalisées avec un microscope confocal Leica SP5 II à l'objectif xlO « dry » en 1024 x 1024 pixels. Pour chaque condition, les images ont été réalisées avec les mêmes paramètres d'acquisition.  The images were made with a Leica SP5 II confocal microscope with the x10 "dry" objective at 1024 x 1024 pixels. For each condition, the images were made with the same acquisition parameters.
3. Analyse d'images 3. Image Analysis
Les images sont analysées à l'aide du logiciel d'analyse d'image Leica QWin. Le contour des colonies de cellules ou clones est tracé pour en déterminer la surface totale puis la surface marquée après détection du marquage de AQP-3. 4. Analyse statistique The images are analyzed using the Leica QWin image analysis software. The contour of the cell colonies or clones is traced to determine the total area and the marked area after detection of AQP-3 labeling. 4. Statistical analysis
L'analyse statistique consiste en un calcul de la moyenne, de l'écart type et de l'intervalle de confiance (a = 0,05) du rapport surface marquée par TAQP3 sur le nombre de cellules présentes dans un clone amenant à distinguer plusieurs tailles de clones correspondant donc au potentiel clonogénique différents des cellules leur ayant donné naissance.  The statistical analysis consists of a calculation of the mean, the standard deviation and the confidence interval (a = 0.05) of the TAQP3-labeled surface area ratio on the number of cells present in a clone leading to several differences. clone sizes therefore corresponding to the different clonogenic potential of the cells giving rise to them.
La significativité des différences de rapports de surfaces observées entre les témoins et les traités a été mesurée par le test de Student (corrélé au test F). Le test de Student est dit significatif si sa valeur est inférieure à 0,05.  The significance of the differences in surface ratios observed between the controls and the treatments was measured by the Student's test (correlated with the F test). The Student's test is said to be significant if its value is less than 0.05.
Résultats Results
Les résultats sont présentés sur les Figures 1 à 3 et le tableau 1. The results are shown in Figures 1 to 3 and Table 1.
Dans la Figure 1, l'activité est exprimée comme étant la quantité d'AQP3 dans chaque clone, tandis que dans les Figures 2 et 3, l'activité est exprimée comme le pourcentage d'AQP3 par cellule. Dans la figure 1, on distingue les clones (colonies) en trois sous- catégories, selon leur taille correspondant à la surface couverte par la cellule- mère et les cellules filles. La taille de la colonie dépend directement du potentiel de clonogénicité de la cellule-mère. In Figure 1, the activity is expressed as the amount of AQP3 in each clone, while in Figures 2 and 3 the activity is expressed as the percentage of AQP3 per cell. In Figure 1, we distinguish the clones (colonies) in three subcategories, according to their size corresponding to the area covered by the mother cell and the daughter cells. The size of the colony depends directly on the potential of clonogenicity of the mother cell.
Les clones de petite taille (0 à 100 000 micron2) sont issus de kératinocytes à faible potentiel de clonogénicité. Small clones (0 to 100,000 micron 2 ) are derived from keratinocytes with a low potential for clonogenicity.
Les clones de taille moyenne (100 000 à 200 000 micron2) sont issus de kératinocytes à potentiel moyen de clonogénicité. The medium size clones (100,000 to 200,000 micron 2 ) are derived from keratinocytes with a medium potential for clonogenicity.
Les clones de grande taille (> 200 000 micron2) sont issus de kératinocytes-souches à fort potentiel de clonogénicité. Large clones (> 200 000 micron 2 ) are derived from keratinocytes-strains with a high potential for clonogenicity.
On observe sur la Figure 1 que le tocophérol agit plus spécifiquement sur les cellules issues de kératinocytes-souches qui forment les plus grandes colonies. Le phosphate de tocophérol présente une activité significative sur l'expression de l'AQP-3 pour les cellules issues de kératinocytes à fort potentiel de clonogénicité par rapport à l'expression mesurée pour les cellules issus de kératinocytes à plus faible potentiel de clonogénicité. On observe un effet plus intense sur l'expression totale de l'AQP-3 d'une colonie de cellules issues de kératinocytes-souches, par rapport à l'effet mesuré sur les colonies issues de cellules à potentiel de clonogénicité moyen ou faible (cellules d'amplification). Pour les clones issus de cellules d'amplification, l'effet est plus faible que pour les kératinocytes-souches à fort potentiel de clonogénicité. Pour ces cellules à plus faible potentiel de clonogénicité, l'effet reste cependant significativement supérieur à celui du témoin non traité, ce qui montre une efficacité du phosphate de tocophérol phosphate sur l'expression de l'AQP-3 sur plusieurs types de kératinocytes. It is observed in Figure 1 that tocopherol acts more specifically on the cells derived from keratinocytes-strains which form the largest colonies. The tocopherol phosphate exhibits a significant activity on the expression of AQP-3 for cells derived from keratinocytes with a high potential for clonogenicity compared with the expression measured for cells derived from keratinocytes with a lower potential for clonogenicity. A more intense effect is observed on the total expression of AQP-3 in a colony of cells derived from keratinocytes-strains, compared with the effect measured on the colonies derived from cells with medium or low clonogenicity potential ( amplification cells). For clones derived from amplification cells, the effect is lower than for keratinocytes-strains with a high potential for clonogenicity. For these cells with a lower potential for clonogenicity, however, the effect remains significantly greater than that of the untreated control, which shows an efficacy of phosphate tocopherol phosphate on the expression of AQP-3 on several types of keratinocytes.
L'effet est cependant beaucoup plus intéressant pour les kératinocytes souches. Non seulement les cellules filles issues de ces cellules souches expriment individuellement une plus grande quantité d'AQP-3, mais en plus, au total, les colonies formées étant de taille plus importante, l'expression totale de l'aquaporine au niveau de la colonie est bien significativement supérieure à l'expression de l'AQP-3 mesurée pour les colonies formées à partir de cellules à moindre potentiel de clonogénicité.  The effect is however much more interesting for stem keratinocytes. Not only do the daughter cells from these stem cells individually express a greater amount of AQP-3, but in addition, in total, the colonies formed being larger in size, the total expression of aquaporin at the level of the colony is significantly greater than the expression of AQP-3 measured for colonies formed from cells with lower potential for clonogenicity.
On observe également sur la Figure 2 un effet-dose important : quand on augmente la concentration en phosphate de tocophérol dans le milieu, l'expression de l'AQP-3 augmente de façon importante. A significant dose effect is also observed in FIG. 2: when the concentration of tocopherol phosphate in the medium is increased, the expression of AQP-3 increases significantly.
Le tableau 1 ci-dessous indique les valeurs moyennes de l'expression de l'AQP3 par cellule issue d'une colonie produite par un kératinocyte à fort potentiel de clonogénicité. Table 1 below shows the average values of the expression of AQP3 per cell derived from a colony produced by a keratinocyte with a high potential for clonogenicity.
Figure imgf000014_0001
Figure imgf000014_0001
La figure 3, issue du tableau 1, montre que l'effet obtenu sur les cellules des clones de grande taille pour le phosphate de tocophérol est du même ordre de grandeur que celui obtenu pour le témoin positif, l'extrait 6'Ajuga turkestanica. L'association des deux actifs montre elle-même sensiblement une addition de l'effet stimulant sur l'expression d'aquaporine 3, ce qui rend cette association particulièrement intéressante dans des compositions cosmétiques visant à hydrater la peau, et plus particulièrement l'épiderme. FIG. 3, from Table 1, shows that the effect obtained on the cells of large clones for tocopherol phosphate is same order of magnitude as that obtained for the positive control, extract 6'Ajuga turkestanica. The combination of the two active agents itself substantially indicates an addition of the stimulating effect on the expression of aquaporin 3, which makes this combination particularly advantageous in cosmetic compositions intended to moisturize the skin, and more particularly the epidermis .
Conclusions II a été mis en évidence que le phosphate de tocophérol stimule significativement l'expression de l'aquaporine 3 sur les clones issus des kératinocytes souches à fort potentiel de clonogénicité. Conclusions It has been demonstrated that tocopherol phosphate significantly stimulates the expression of aquaporin 3 on clones derived from stem keratinocytes with a high potential for clonogenicity.
Le phosphate de tocophérol stimule significativement l'expression de l'aquaporine 3 quelle que soit la taille des clones.  Tocopherol phosphate significantly stimulates the expression of aquaporin 3 irrespective of the size of the clones.
Le phosphate de tocophérol a une efficacité particulièrement significative pour réguler les flux hydriques et de glycérol dans l'épiderme, permettant ainsi une meilleure hydratation des couches basales de l'épiderme.  Tocopherol phosphate has a particularly significant effectiveness in regulating the hydrous and glycerol fluxes in the epidermis, thus allowing better hydration of the basal layers of the epidermis.
En outre, les résultats montrent que l'association du phosphate de tocophérol et d'un extrait d'Ajuga turkestanica stimule de façon plus intense l'expression de l'aquaporine 3 que chaque ingrédient testé seuls. L'effet bénéfique de cette association semble spécifique de cette population cellulaire puisque l'effet n'est pas retrouvé pour les cellules des clones de plus petite taille (cellules filles dites d'amplification).  In addition, the results show that the combination of tocopherol phosphate and an extract of Ajuga turkestanica more intensively stimulates the expression of aquaporin 3 than each ingredient tested alone. The beneficial effect of this association seems specific for this cell population since the effect is not found for the cells of the smaller clones (so-called amplification daughter cells).
L'association de l'extrait d'Ajuga turkestanica et du phosphate de tocophérol est donc particulièrement avantageuse pour stimuler l'expression de l'aquaporine 3 dans les progéniteurs kératinocytaires à fort potentiel clonogénique (cellules issues de cellules souches). Cette association est donc particulièrement recommandée pour cibler cette population particulière de cellules épidermiques, dans des compositions cosmétiques dont l'application sur la peau permet de renforcer la capacité d'adaptation de ces cellules épidermiques à des stress osmotiques et de favoriser le maintien de leur fort potentiel clonogénique.  The combination of Ajuga turkestanica extract and tocopherol phosphate is therefore particularly advantageous for stimulating the expression of aquaporin 3 in keratinocyte progenitors with high clonogenic potential (cells derived from stem cells). This combination is therefore particularly recommended for targeting this particular population of epidermal cells, in cosmetic compositions whose application to the skin makes it possible to enhance the ability of these epidermal cells to adapt to osmotic stress and to promote the maintenance of their strong clonogenic potential.
L'association du phosphate de tocophérol avec l'extrait dAjuga turkestanica, agent hydratant connu pour son action sur l'AQP-3, a un effet bénéfique supplémentaire sur l'expression de l'AQP-3. L'effet est spécifique aux clones issus des kératinocytes souches qui ont un rôle primordial dans le renouvellement de l'épiderme du fait de cette capacité à produire des clones contenant une grande quantité de cellules. L'effet de stimulation de l'AQP-3 s'étend ainsi au plus grand nombre de cellules-filles. Ceci permet une meilleure résistance au stress osmotique de ces cellules et assure le maintien d'une hydratation suffisante au niveau de l'épiderme. The combination of tocopherol phosphate with the extract of Ajuga turkestanica, a moisturizing agent known for its action on AQP-3, has an additional beneficial effect on the expression of AQP-3. The effect is specific to clones derived from stem keratinocytes which have a primordial role in the renewal of the epidermis due to this ability to produce clones containing a large amount of cells. The stimulatory effect of AQP-3 thus extends to the largest number of daughter cells. This allows a better resistance to the osmotic stress of these cells and ensures the maintenance of sufficient hydration in the epidermis.
Exemple 2 - Compositions cosmétiques Example 2 - Cosmetic Compositions
Le phosphate de tocophérol est utilisé à titre d'agent hydratant dans les compositions cosmétiques suivantes. Tocopherol phosphate is used as a moisturizing agent in the following cosmetic compositions.
1 - Lotion 1 - Lotion
On prépare une solution aqueuse comprenant les actifs suivant (pourcentage en poids) : An aqueous solution comprising the following active ingredients (percentage by weight) is prepared:
% %
Phosphate de tocophérol 0,050.05 Tocopherol Phosphate
Glycérol 3,0Glycerol 3.0
Solution à 5% d'extrait d'Ajuga turkestanica 0,01 Extrait de Malva sylvestris 0,25% solution of Ajuga extract turkestanica 0,01 Malva sylvestris extract 0,2
Hétérosides de Centella asiatica 0,02Heterosides of Centella asiatica 0,02
Acides hyaluronique de haut et de bas poids moléculaire 0,05High and low molecular weight hyaluronic acids 0.05
Excipients qsp 100 Excipients qs 100
La lotion est appliquée quotidiennement sur le visage. The lotion is applied daily on the face.
2 - Crème de jour hydratante 2 - Moisturizing day cream
On prépare une émulsion hydratante dont la formule est indiquée -dessous (% en oids) A moisturizing emulsion is prepared whose formula is indicated below (% by weight)
% %
Phase A Phase A
Phosphate de tocophérol 0,1 Solution à 1% en extrait de Vanda coerulea 0,3 Tocopherol phosphate 0.1 1% solution of Vanda coerulea extract 0.3
Phénoxyéthanol 0,5 Gomme xanthane 0,2Phenoxyethanol 0.5 Xanthan gum 0.2
Acrylates/C20-30 alkylacrylate crospolymères 0,15Acrylates / C20-30 alkylacrylate crospolymers 0.15
EDTA tétrasodique 0,1Tetrasodium EDTA 0,1
Eau qs Phase B Water qs Phase B
Polyisobutène hydrogéné 4 Hydrogenated polyisobutene 4
Squalane 3Squalane 3
Caprylique/caprique triglycéride 3Caprylic / capric triglyceride 3
Pentylène glycol 3 Glycéryl stéarate 3Pentylene Glycol 3 Glyceryl Stearate 3
PEG-100 stéarate 2,5PEG-100 stearate 2.5
Cire d'abeilles 1,5Beeswax 1,5
Dicaprylyl carbonate 1,5Dicaprylyl carbonate 1,5
Cétyl alcool 1 Stéaryl alcool 1Cetyl alcohol 1 stearyl alcohol 1
Diméthicone 1 Phase C Dimethicone 1 Phase C
Hydroxyde de sodium 0,04 0.04 sodium hydroxide
Eau qsp 100 Water qs 100
On disperse les gélifiants de la phase A dans l'eau puis on chauffe à 80-85°C, avant de solubiliser les composés. Les composés de la phase B sont chauffés à 85°C pour former une phase homogène. On émulsionne la phase A dans la phase B à l'aide d'un mélangeur Ystral. The phase A gelling agents are dispersed in water and then heated to 80-85 ° C, before solubilizing the compounds. The compounds of phase B are heated to 85 ° C to form a homogeneous phase. Phase A is emulsified in phase B using a Ystral mixer.
L'émulsion huile/eau est finalement neutralisée à l'aide d'une solution aqueuse d'hydroxyde de sodium, puis refroidie.  The oil / water emulsion is finally neutralized with an aqueous solution of sodium hydroxide, and then cooled.
La composition obtenue est une crème hydratante destinée à être appliquée sur le visage ou une partie du visage. 3 - Crème pour les veux  The composition obtained is a moisturizer intended to be applied to the face or part of the face. 3 - Cream for the wanna
On prépare sous la forme d'une émulsion huile-dans-eau comprenant les actifs suivant (pourcentages en poids) : It is prepared in the form of an oil-in-water emulsion comprising the following active ingredients (percentages by weight):
%  %
Phosphate de tocophérol 0,3  Tocopherol phosphate 0.3
Solution d'extrait d'Ajuga turkestanica 0,1 Glycérol 5,0 Ajuga extract solution turkestanica 0.1 Glycerol 5.0
Excipients et eau qs 100  Excipients and water qs 100
Ces ingrédients actifs sont inclus dans la formule pour réaliser une émulsion huile-dans-eau selon le même procédé que l'exemple précédent. These active ingredients are included in the formula for producing an oil-in-water emulsion according to the same process as the previous example.
Une application quotidienne de cette composition cosmétique autour des yeux, conduit à une amélioration significative de l'hydratation de la peau de cette zone. 4 - Sérum comprenant le phosphate d'alpha-tocophérol sodique  Daily application of this cosmetic composition around the eyes leads to a significant improvement in the hydration of the skin of this zone. 4 - Serum comprising alpha-tocopherol sodium phosphate
On prépare un sérum selon la formule suivante (%en poids) : A serum is prepared according to the following formula (% by weight):
Phase A Phase A
Eau purifiée 60,2%  Purified water 60.2%
Conservateurs 0,7% Preservatives 0.7%
Phase B  Phase B
Carbomer (Carbopol® Ultrez 10) 0,5%  Carbomer (Carbopol® Ultrez 10) 0.5%
Phase C Phase C
EDTA tétrasodique 0,2%  0.2% tetrasodium EDTA
Hydroxyde de sodium 0,2% Sodium hydroxide 0.2%
Glycérol 3,5% Glycerol 3,5%
Acide ascorbique <0,1%  Ascorbic acid <0.1%
Butylène glycol 1-3 2,0% Butylene glycol 1-3 2.0%
Méthyl gluceth-20 1,8% Methyl gluceth-20 1.8%
Eau purifiée 6,0% Purified water 6.0%
Phase D Phase D
Phosphate de tocophérol (sel de sodium) 0,1%  Tocopherol phosphate (sodium salt) 0.1%
Sorbitol 0.3% Sorbitol 0.3%
Alginate de sodium 0,1%  Sodium alginate 0.1%
Carboxymethylcellulose de sodium <0,1% Sodium carboxymethylcellulose <0.1%
Polyvinyl alcool <0,1% Polyvinyl alcohol <0.1%
Emumlmetik® 300 IP 0,5% Emumlmetik® 300 IP 0.5%
Emulmetik® 930 0,5% Emulmetik® 930 0.5%
Butylène glycol 1-3 1,0% Butylene glycol 1-3 1.0%
Glycérol 1,0% Glycerol 1.0%
Antioxydants 0,2% Eau purifiée qsp 100% 0.2% antioxidants Purified water qs 100%
On homogénéise les phospholipides de la phase D à l'Ultraturrax, avec le butylène glycol et le glycérol pendant 20 minutes. The phospholipids of the D phase are homogenized with the ultraturrax, with butylene glycol and glycerol for 20 minutes.
On ajoute les autres composés de la phase D, puis l'eau purifiée. The other compounds of phase D are added, followed by the purified water.
La phase lamellaire obtenue est cisaillée pendant 20 minutes à l'Ultraturrax pour former la dispersion de liposomes. The lamellar phase obtained is sheared for 20 minutes with Ultraturrax to form the liposome dispersion.
Le Phosphate de tocophérol sous forme de sel est inclus dans le sérum à titre d'agent actif et se trouve encapsulé dans les liposomes ainsi préparés.  The tocopherol phosphate in salt form is included in the serum as an active agent and is encapsulated in the liposomes thus prepared.
Séparément, on chauffe les composés de la phase A à 80°C.  Separately, the compounds of phase A are heated to 80 ° C.
A température ambiante, on ajoute les composés de la phase B, puis on laisse gonfler le gel avant d'ajouter les composés de la phase C dans le gel précédemment formé.  At room temperature, the compounds of phase B are added, and the gel is allowed to swell before adding the compounds of phase C into the previously formed gel.
On ajoute la dispersion de liposomes à la phase aqueuse précédemment préparée.  The liposome dispersion is added to the previously prepared aqueous phase.
Le sérum comprend des liposomes multilamellaires dans lesquels est encapsulé le sel de phosphate de tocophérol.  The serum comprises multilamellar liposomes in which the tocopherol phosphate salt is encapsulated.
Le sérum est appliqué sur la peau du visage et du coup, en particulier sur les zones présentant des signes de déshydratation ou consécutifs à une exposition à des stress environnementaux (froid ou UV) provoquant un dessèchement de la peau.  The serum is applied to the skin of the face and blow, especially on areas showing signs of dehydration or due to exposure to environmental stresses (cold or UV) causing drying of the skin.

Claims

REVENDICATIONS
1. Utilisation dans une composition cosmétique, du phosphate de tocophérol ou d'un de ses sels, comme agent destiné à restaurer l'état d'hydratation d'une peau sèche ou d'une peau dont la barrière hydrique est altérée, en soutenant sur le long terme le renouvellement cellulaire de l'épiderme altéré au cours du temps en situation de déshydratation, ladite composition contenant en outre un excipient cosmétiquement acceptable. 1. Use in a cosmetic composition, of tocopherol phosphate or of a salt thereof, as an agent intended to restore the hydration state of dry skin or of a skin whose water barrier is impaired, by supporting in the long term the cellular renewal of the epidermis altered over time in a dehydration situation, said composition also containing a cosmetically acceptable excipient.
2. Utilisation selon la revendication 1, caractérisée en ce que ledit sel est un sel de métal alcalin.  2. Use according to claim 1, characterized in that said salt is an alkali metal salt.
3. Utilisation selon l'une des revendications 1 ou 2, caractérisée en ce que ledit sel est un sel de sodium.  3. Use according to one of claims 1 or 2, characterized in that said salt is a sodium salt.
4. Utilisation selon l'une des revendications 1 à 3, caractérisée en ce que ladite composition contient de 0,001 % à 5% en poids, de préférence de 0,01 à 1%, de phosphate de tocophérol en poids sec.  4. Use according to one of claims 1 to 3, characterized in that said composition contains from 0.001% to 5% by weight, preferably from 0.01 to 1%, of tocopherol phosphate dry weight.
5. Utilisation selon l'une des revendications 1 à 4, caractérisée en ce que ladite composition contient en outre une ou plusieurs molécules et/ou un ou plusieurs extraits végétaux présentant des propriétés hydratantes, tels que les glycols, en particulier le glycérol, ou des polyols naturels, des céramides naturels ou de synthèse, l'urée, l'acide hyaluronique, l'acide lactique, un extrait de Vanda coerulea ou encore un extrait ù'Ajuga turkestanica.  5. Use according to one of claims 1 to 4, characterized in that said composition further contains one or more molecules and / or one or more plant extracts having moisturizing properties, such as glycols, in particular glycerol, or natural polyols, natural or synthetic ceramides, urea, hyaluronic acid, lactic acid, an extract of Vanda coerulea or an extract of Ajuga turkestanica.
6. Utilisation selon l'une des revendications 1 à 5, caractérisée en ce que ladite composition est sous la forme d'un sérum, d'une lotion, d'une crème, d'un hydrogel, d'un masque, d'un stick ou d'un patch.  6. Use according to one of claims 1 to 5, characterized in that said composition is in the form of a serum, a lotion, a cream, a hydrogel, a mask, a stick or patch.
7. Utilisation selon la revendication 1, caractérisée en ce que l'agent renforce la capacité d'adaptation des cellules de la peau à un stress osmotique et/ou favorise leur potentiel clonogénique.  7. Use according to claim 1, characterized in that the agent enhances the ability of skin cells to adapt to osmotic stress and / or promotes their clonogenic potential.
8. Utilisation selon la revendication 1, caractérisée en ce que l'agent restaure l'état d'hydratation des kératinocytes de l'épiderme.  8. Use according to claim 1, characterized in that the agent restores the hydration state of the keratinocytes of the epidermis.
9. Utilisation selon la revendication 1, caractérisée en ce que l'agent restaure l'état d'hydratation d'une peau mature et sèche.  9. Use according to claim 1, characterized in that the agent restores the hydration state of a mature and dry skin.
10. Utilisation selon la revendication 1, caractérisée en ce que ledit phosphate de tocophérol stimule l'expression de l'aquaporine de type 3 dans les kératinocytes souches de la peau dont le potentiel clonogénique est réduit, lorsque les cellules de l'épiderme sont soumises à un stress osmotique dû au froid ou plus généralement à un environnement externe desséchant. 10. Use according to claim 1, characterized in that said tocopherol phosphate stimulates the expression of type 3 aquaporin in keratinocytes stem skin whose clonogenic potential is reduced, when the cells of the epidermis are subjected to osmotic stress due to the cold or more generally to an external desiccating environment.
11. Méthode de soin cosmétique de la peau pour maintenir ou restaurer l'état d'hydratation des peaux sèches, qui sont exposées au froid, qui sont dans un environnement desséchant dû à un air sec, qui sont exposées à des actions régulières de nettoyage ou de démaquillage, ou encore qui sont exposées à des polluants atmosphériques domestiques ou extérieurs, ladite méthode étant caractérisée en ce qu'elle comprend l'application sur au moins une partie de la peau du visage ou du corps subissant un stress osmotique, d'une quantité efficace de phosphate de tocophérol ou d'un de ses sels.  11. Cosmetic skin care method for maintaining or restoring the hydration state of dry skin, which is exposed to the cold, which is in a desiccating environment due to dry air, which are exposed to regular cleaning actions or removing makeup, or which are exposed to atmospheric pollutants, domestic or external, said method being characterized in that it comprises the application on at least a portion of the skin of the face or the body undergoing osmotic stress, of an effective amount of tocopherol phosphate or a salt thereof.
PCT/FR2014/053276 2013-12-20 2014-12-12 Use of tocopherol phosphate as a hydrating agent WO2015092227A1 (en)

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FR1363326 2013-12-20

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