• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a cosmetic and / or dermatological and / or therapeutic composition, comprising, as active ingredient, a thermal water rich in mineral salts, for improving the barrier function of the epithelial cells, including the cells of the skin. This action is carried out through two different biochemical pathways: on the one hand favoring the synthesis of filaggrin to restore the barrier function of Stratum corneum, on the other hand by promoting the synthesis of claudin 4 to restore the barrier function of Stratum granulosum.
    公开号:FR3016127A1
    申请号:FR1400018
    申请日:2014-01-07
    公开日:2015-07-10
    发明作者:Luc Lefeuvre
    申请人:DERMATOLOGIQUES D URIAGE LAB；
    IPC主号:
    专利说明:

    [0001] The technical field of the present invention is that of compositions intended to enhance the barrier function of human epithelial coating cells, for example keratinocyte cells.
    [0002] The cells of the skin, mucous membranes and other epithelial lining cells are at the interface between the inside of the human body and the outside environment. External aggression against these cells leads to the deterioration or even the destructuring of their barrier function. The barrier function of the epithelial cells, for example the cells of the skin, is essential for the management of hydration (avoidance of cutaneous drying or on the contrary of hyperhydration) and for the protection vis-à-vis external aggressions ( allergens, bacteria). A disruption of the barrier function may in particular cause inflammation or dryness of the skin. The barrier function results from epidermal differentiation, a sequential and oriented process in which cells undergo numerous morphological and metabolic changes resulting in stratification of the epidermis and formation of the stratum corneum. The exterior of the human epidermis is mainly Stratum corneum or stratum corneum and Stratum granulosum 25 or granular layer. The Stratum corneum is mainly composed of dead but biochemically active cells: corneocytes. These are the cells directly in contact with the outside. Stratum granulosum is below the Stratum 30 corneum and mainly provides a barrier function consisting of the tight junctions of the cells. The tight junctions (Tight Junctions according to the English word) represent the junctions between the cells (cell-cell junction). These junctions are composed of several families of transmembrane proteins such as claudines, occludin and adhesion molecules (ZO-1, ZO2, ZO-3, etc.). These tight junctions are present in the epithelial cells, especially in the skin.
    [0003] Claudin 1, claudin 4, occludin and ZO-1 are found among the proteins present in the upper layers of the epidermis (place of differentiation of keratinocytes), in particular the Stratum corneum of the epidermis. These proteins play an important role in the protection of the cutaneous barrier by preventing the entry of small molecules and in maintaining the integrity of the upper layers of the epidermis (reinforced cohesion between corneocytes).
    [0004] We are actively looking for compositions restoring the barrier function of one or other of the Stratums mentioned above, in particular by promoting the secretion of one of the abovementioned proteins. The use of essential oils in cosmetic compositions is known to restore the barrier function of the skin. In FR-2960436, the essential oil of cedar is used to stimulate the production of claudin 1, a protein of the family of claudines known to restore the tight junctions of cutaneous cells. The use of active ingredients from the yeast Torulaspora delbrueckii (FR-2979541), the seeds of the plant Kniphofia uvaria (FR-2985187), or a hydrolyzate of Cichorium intybus root (FR-2987744) is also known. ), to restore or improve the barrier function of the skin. We are therefore actively seeking new active principles to improve the state of the barrier function of the skin or more generally epithelial cells. Active and inexpensive active agents are also actively being sought because most of the current known active ingredients are derived from biological / biological / chemical processes, making them expensive and complex products to produce. The present invention satisfies this need by providing cosmetic and / or dermatological and / or therapeutic compositions comprising, as active ingredient, mineral water. The Applicant has discovered in a completely fortuitous and surprising manner that a composition comprising as an active principle a mineral water rich in trace elements and mineral salts makes it possible to improve the barrier function of the epithelial cells through at least two distinct mechanisms. and complementary. The subject of the invention is therefore a cosmetic and / or dermatological and / or therapeutic composition comprising, as active principle, a mineral water comprising: between 40 mg / L and 600 mg / L of calcium, and / or salts and or derivatives thereof, between 12.5 mg / L and 125 mg / L magnesium, and / or salts and / or derivatives thereof, between 0.455 mg / L and 45, 5 mg / L of potassium, and / or salts and / or derivatives thereof, - between 23.6 mg / L and 2360 mg / L of sodium, and / or salts and / or derivatives thereof the other ingredients being constituted by compounds which are acceptable in the cosmetic and / or dermatological and / or therapeutic fields, for its use in the restoration and / or improvement of the barrier function of human epithelial cells. According to one characteristic of the invention, the calcium and magnesium and / or the salts and / or the derivatives thereof present in the mineral water are in a mass ratio Ca / Mg of between 1 and 10. According to Another characteristic of the invention is that the mineral water is in a mass proportion of between 1% and 100%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 5%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 12%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 27%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 50%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 60%. According to yet another characteristic of the invention, the mineral water is constituted by Uriage Thermal Water.
    [0005] According to another characteristic of the invention, calcium, magnesium and sodium and / or their salts and / or derivatives are present in mineral water in concentrations of 42.7 mg / L and 21.2 mg respectively. / L and 4.8 mg / L. According to yet another characteristic of the invention, the calcium and / or its salts and / or its derivatives is present in mineral water at a concentration of 140 mg / l. According to another characteristic of the invention, calcium, magnesium, potassium and sodium and / or their salts and / or derivatives are present in mineral water in concentrations of 236 mg / L, 28.1 mg / L, 29.9 mg / L and 982 mg / L. According to yet another characteristic of the invention, the composition according to the invention is integrated into one or more of the following medical devices: a nasal spray, nasal unidoses, and ocular unidoses. According to yet another feature of the invention, the composition is used to stimulate the production of claudin 4 by epithelial cells. According to yet another characteristic of the invention, the composition is used to stimulate the production of filaggrins by the epithelial cells. According to yet another characteristic of the invention, the epithelial cells are keratinocytes. A first advantage of the composition according to the invention is to significantly improve the barrier function of the epithelial cells. Another advantage of this invention is the action on restoring the barrier function of epithelial cells via two different biochemical pathways. Another advantage of the invention is the low cost of a mineral water rich in trace elements and inorganic salts as active principle, compared to the cost of an active ingredient derived from a biological / biochemical / chemical process. Another advantage of the invention is its total safety for the human body.
    [0006] Other features, details and advantages of the invention will be better understood with the aid of the additional description which follows. Graph 1 represents a quantity dosed in ng / l of filaggrin by assay in normal untreated human keratinocytes (controls), treated with Uriage Thermal Water at 3 and 10%, and treated with calcium (CaCl 2) at 1.5 mM (positive control). Graph 2 represents a quantity dosed in ng / l of claudin 4 (CLDN4) in normal untreated human keratinocytes (controls), treated with Uriage Thermal Water at 3 and 10%, and treated with calcium (CaCl 2 ) at 1.5 mM (positive control). By barrier function of epithelial cells is meant the properties of the upper layers of epithelial cells (in contact with an environment outside the human body), including keratinocyte cells, which concern the protection of the body against external aggressions (allergens, bacteria, irritants , etc.) and the regulation of internal body fluids (water, etc.). By mineral water rich in trace elements and mineral salts is meant a mineral water comprising, relative to common water (tap or same bottle), at least high proportions of the following elements: calcium, magnesium, potassium, sodium, as well as salts and derivatives thereof. In the present invention, the mineral water presented as the active ingredient is Uriage Thermal Water or ETU which comprises in particular: - A dry residue of 11000 mg / L - Calcium: 600 mg / L - Magnesium: 125 mg / L - Potassium: 45.5 mg / L - Sodium: 2360 mg / L 35 - Sulfates: 2860 mg / L - Chlorides: 3500 mg / L - Bicarbonates: 390 mg / L - Silicon: 42 mg / L - Zn: 160 pg / L - Mn: 154 pg / L - Cu: 75 pg / L - Fe: 15 pg / L Uriage Thermal Water or ETU is recognized as one of the most balanced mineralized thermal waters in trace elements and mineral salts. ETU is marketed by URIAGE. In particular, it has an effective moisturizing action when applied as a spray locally (URIAGE commercial data). The authors of the present invention surprisingly discovered that the local application of ETU made it possible: to stimulate the production of claudin 4, a protein which is a marker of differentiation of epithelial cells and known in particular to promote the formation of tight junctions. These tight junctions are particularly found in the Stratum granulosum, - stimulate the production of filaggrin, a protein very involved in the barrier function of Stratum corneum. This protein notably reinforces the cohesion of the corneocytes with the lipidic cement. Thus, a cosmetic and / or dermatological and / or therapeutic composition comprising ETU allows the maintenance and enhancement of the skin barrier function through two different biochemical mechanisms. It is obvious that its local application is within cosmetic and / or dermatological and / or therapeutic compositions whose other ingredients are acceptable compounds in these fields. The same is true when the ETU is applied internally to the body by means of a medical device, for example a medical spray device intended to introduce the composition according to the invention into human nostrils such as as a nasal spray. The composition according to the invention can also be very well integrated into intended single doses or nostrils or human eyes. It is obvious to those skilled in the art that equivalent mineral waters are possible if they are used in adequate proportions for the important elements underlined above or the salts and derivatives thereof. Thus, one can very well use in appropriate proportions Avene Thermal Water marketed by the company Pierre Fabre, which comprises 42.7 mg / l of calcium, 21.2 mg / l of magnesium, 4.8 mg / Sodium L, or Thermal Water La RochePosay marketed by the company La Roche-Posay, which includes 140 mg / L of calcium, or the Thermal Water of Saint-Gervais, which includes 236 mg / L of calcium, 28.1 mg / L magnesium, 29.9 mg / L potassium and 982 mg / L sodium. Typically, calcium and magnesium are naturally present in the mineral waters according to the invention in a respective Ca / Mg mass ratio of between 1 and 10.
    [0007] It is entirely possible to combine the mineral water included in the composition according to the invention with other active ingredients that are relevant in the cosmetic, dermatological or therapeutic fields. With regard to the therapeutic field, the case where the ETU is used to reinforce the barrier function for prophylactic purposes can be considered in particular. In the following test, the effect of ETU on the production of two proteins of interest involved in the differentiation of cultured keratinocytes was evaluated. The two dosed proteins are claudin 4 and filaggrin. The cells used in this test are normal human keratinocytes, extracted from abdominal plastid samples. Test principle Normal human keratinocytes are inoculated into a 24-well plate and then treated with the different products for 48 hours. The actives were stored at room temperature and protected from light for the duration of the experiments. For the different thermal waters, two non-cytotoxic concentrations are evaluated: 10 and 3%. The rest of the water used in the test is water from the cell.
    [0008] A control is used in this study: Calcium (Calcium chloride - Sigma C2661) at 1.5 mM, positive control of keratinocyte differentiation. Treatment of cells The cells are seeded at a density of 100,000 cells per well in complete KSFM medium. The products, tested at different concentrations in an uncompleted medium, are placed in contact with the cells for 48 hours at + 37 ° C., 5% CO 2. Each product concentration is evaluated in sixtiplate. Determination of claudin 4 and filaggrin The amount of these proteins of interest contained in the supernatants and cell pellets is evaluated with an enzyme-linked immunosorbent assay (ELISA) of the proteins, the absorbance being measured. at 450 nm. The following kits are used: "ELISA Kit For Filaggrin" (USCN Life Science E98103Hu). "ELISA Kit For Claudin 4" (USCN Life Science E95294Hu). The ELISA assays are carried out here in the supernatants. Two samples are dosed in duplicate; therefore, 4 optical density (OD) values are obtained for each condition. Data Processing The optical densities obtained for the standard references are plotted on a graph. The known concentrations of filaggrin, claudin 4 (CLDN4) in ng / ml are plotted on the abscissa and the ODs on the ordinate. A calibration line is thus determined, and allows the conversion of the OD data of the samples to the amount of protein in ng / ml. Results for Filaggrin The results of the filaggrin assay are shown in Chart 1. Calcium induced a very significant increase in filaggrin production in cell supernatants of + 199% ± 0. Uriage Thermal Water induced significant increases of + 344% ± 24 and + 408% ± 34 respectively at doses of 10 and 3%.
    [0009] Results for claudin 4 The results of the filaggrin assay are shown in Chart 2. Calcium induces a very significant increase in the production of claudin 4 in cell supernatants of +1805% ± 263. Uriage induces a significant increase in the production of claudin 4 at a dose of 10% with an increase of +880% ± 132. The 3% dose induces an increase of + 688% + 472% which is not significant. Conclusion ETU induces a significant increase in the production of claudin 4 and filaggrin, except in the case of 3% ETU for claudin 4. Thus, the ETU strengthens the barrier function of the skin by stimulating the production of specific proteins that mark the differentiation of epithelial cells. Examples of compositions comprising ETU (INCI name EU: "Uriage Thermal Spring Water") according to the invention Example 1: Cleansing Oil INCI Name EU% (mass) Aqua qsp Uriage Thermal Spring Water 5 Borage seed oil 0,01 aminopropanediol amides Glycerin 19 Hydrogenated starch hydrolyzate 15.4 PEG-7 glyceryl cocoate 2 Sodium cocoyl glutamate 1.8 Sodium laureth sulfate 1.8 Sodium laureth-8 sulfate 1.62 Ceteareth-60 myristyl glycol 1 Polysorbate 20 0.97 Coco-glucoside 0 , 66 Glyceryl oleate 0.66 Sodium chloride 0.646 Citric acid 0.54 Magnesium laureth sulfate 0.45 Sodium oleth sulfate 0.45 Polyquaternum-10 0.364 Magnesium laureth-8 sulfate 0.36 PEG-75 shea butter glycerides 0.25 Magnesium oleth sulfate 0.09 Sodium acetate 0.006 Example 2: Hand cream INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 12 Borage seed oil 0.1 aminopropane diol amides Glycerin 3 Phenoxyethanol 0.5 Chlorphenesin 0.2 Acrylates / C10-30 alkyl acrylate crosspolymer 0,17 Glyceryl stearate PEG-100 3 stearate Cetyl alcohol 2 Cetearyl isononoate 4 Squalane 4 Hydrogenated polydecene 8 Dimethicone 1 Tromethamine 0.19 Example 3: Anti-itching milk - O / W Emulsion INCI Name EU% (mass) Aqua qsp Uriage Thermal Spring Water 27 Borage seed oil 0.006 aminopropanediol amides Butyrospermum parkll (shea 5 butter) Cetearyl isononanoate 5 Isodecyl neopentanoate 4 Butylene glycol 3 Glycerin 3 Hydrogenated polydecene 2,5 Dimethicone 2 Squalane 2 Steareth-2 2 Steareth-21 2 Cetyl alcohol 1 Pentaerythrityl distearate 1 Polyacrylate-13 0.6 Brassica campestris sterols 0.5, Chlorphenesin 0.3 Piroctone olamine 0.3 Polyisobutene 0.27 Sodium dextran sulfate 0.2 Citric acid 0.1 o-cymen-5-ol 0.1 Tocopheryl acetate 0.1 Xanthan gum 0.1 Raspberry seed oil / palm oil 0.05 aminopropanediol esters Polysorbate 20 0.045 Sorbitan isostearate 0.04 Asiaticoside 0.02 Phytosphingosine 0.02 Example 4: Cream face INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 50 Borage seed oil 1 aminopropanediol amides Perfume 0,2 C itric acid 0.028 Phenoxyethanol 0.7 Chlorphenesin 0.3 Glycerin 7 Xanthan gum 0.3 Glyceryl stearate PEG-100 1.2 stearate Cetearyl isononanoate 5 Propylheptyl caprylate 3 Pentaerythrityl distearate 2 Cetyl alcohol 0.7 Cetearyl alcohol 2 Glyceryl stearate 1.8 Butyrospermum parkll (shea 5 butter) Tocopheryl acetate 0.5 Dimethicone 1 Cetearyl alcohol cetearyl 2 glucoside o-cymen-5-ol 0.1 Butylene glycol 3 Example 5: oleo-thermal liniment INCI name EU 96 (mass) Uriage Thermal Spring Water 60 Helianthis anuus seed oil Glycerin 3 Butylene glycol 2 Sodium chloride 0.84 Cera alba 1 Pentaerythrityl distearate 1 Magnesium hydroxide 0.5 Octyldodecyl xyloside 0.33 PEG-30 dipolyhydroxystearate 0.33 Magnesium sulfate 1 The examples of compositions illustrated above do not are not limiting and may extend especially to all milks, creams, lotions, and gels, etc. The compositions described above are prepared according to the rules of the art in the field, and in the same way the processes for the preparation of the creams, gels or lotions according to the invention are known and need not be further detailed. . It goes without saying that these examples are not limiting and that one skilled in the art can integrate other active and excipients specific to the cosmetic and / or dermatological and / or therapeutic.
    权利要求:
    Claims (16)
    [0001]
    REVENDICATIONS1. Cosmetic and / or dermatological and / or therapeutic composition comprising as active ingredient a mineral water comprising: between 40 mg / L and 600 mg / L of calcium, and / or salts and / or derivatives thereof, - between 12,5 mg / L and 125 mg / L magnesium, and / or salts and / or derivatives thereof, - between 0,455 mg / L and 45,5 mg / L of potassium, and / or salts and / or derivatives thereof, - between 23.6 mg / L and 2360 mg / L of sodium, and / or salts and / or derivatives thereof, the other ingredients consisting of compounds acceptable in the cosmetic and / or dermatological and / or therapeutic fields, for its use in the restoration and / or improvement of the barrier function of human epithelial cells.
    [0002]
    2. Composition according to claim 1, characterized in that the calcium and magnesium and / or the salts and / or derivatives thereof present in the mineral water are in a mass ratio Ca / Mg of between 1 and 10.
    [0003]
    3. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of between 1% and 100%.
    [0004]
    4. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of 5%.
    [0005]
    5. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of 12%.
    [0006]
    6. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of 27%. 35
    [0007]
    7. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of 50%.
    [0008]
    8. Composition according to claim 1 or claim 2, characterized in that the mineral water is in a mass proportion of 60%.
    [0009]
    9. Composition according to one of the preceding claims 5, characterized in that the mineral water is constituted by Uriage Thermal Water.
    [0010]
    10. Composition according to one of claims 1 to 8, characterized in that the calcium, magnesium and sodium and / or their salts and / or derivatives are present in mineral water in concentrations of 42.7 respectively. mg / L, 21.2 mg / L and 4.8 mg / L.
    [0011]
    11. Composition according to one of claims 1 to 8, characterized in that the calcium and / or its salts and / or its derivatives is present in mineral water at a concentration of 140 mg / l.
    [0012]
    12. Composition according to one of claims 1 to 8, characterized in that calcium, magnesium, potassium and sodium and / or their salts and / or derivatives are present in the mineral water in respective concentrations of 20. 236 mg / L, 28.1 mg / L, 29.9 mg / L and 982 mg / L.
    [0013]
    13. Composition according to one of the preceding claims, characterized in that it is integrated within one or more of the following medical devices: a nasal spray, nasal unidoses, and ocular unidoses.
    [0014]
    14. Composition according to one of the preceding claims for its use to stimulate the production of claudin 4 by the epithelial cells.
    [0015]
    15. Composition according to one of claims 1 to 13 for its use for stimulating the production of filaggrins by epithelial cells.
    [0016]
    16. Composition according to one of the preceding claims, characterized in that the epithelial cells are keratinocytes.
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    法律状态:
    2016-01-21| PLFP| Fee payment|Year of fee payment: 3 |
    2017-01-26| PLFP| Fee payment|Year of fee payment: 4 |
    2018-01-29| PLFP| Fee payment|Year of fee payment: 5 |
    2020-01-30| PLFP| Fee payment|Year of fee payment: 7 |
    2021-01-28| PLFP| Fee payment|Year of fee payment: 8 |
    2022-01-31| PLFP| Fee payment|Year of fee payment: 9 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1400018A|FR3016127B1|2014-01-07|2014-01-07|COMPOSITION FOR THE RESTORATION OF THE BARRIER EFFECT OF EPITHELIAL CELLS|FR1400018A| FR3016127B1|2014-01-07|2014-01-07|COMPOSITION FOR THE RESTORATION OF THE BARRIER EFFECT OF EPITHELIAL CELLS|
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