FR3015291A1 - ANTIPRURIGINOUS COMPOSITION - Google Patents

Abstract

The invention relates to a cosmetic and / or dermatological and / or therapeutic composition intended for the treatment of pruriginous or inflamed skin or mucous membranes via certain particular biochemical mechanisms. The composition comprises, as active principle, mineral water rich in trace elements and mineral salts. It makes it possible to reduce the release of TSLP and to regulate the TRPV1 receptors and the cannabinoid CB1 and CB2 receptors.

Description

The technical field of the present invention is that of compositions intended to treat skin irritated by inflammatory conditions such as pruritus, as well as the pain associated with this problem.

Pruritus is a functional sign and is defined as "a sensation that causes the need to scratch". It can be localized or generalized. Pruritus becomes pathological when it induces scratching lesions. There are many pruritus stimuli, external stimuli (physical or chemical) but also very often endogenous stimuli (histamine, proteases, prostaglandins, neuropeptides). All pruritus stimuli are not known. In the skin, pruritus is recorded by non-myelinated nociceptive C endings (free endings). Typically, itching causes "the need to scratch" and then a painful irritation caused by scratching and subsequent increase in inflammatory phenomena. We can then fall into chronic pruritus. Most current antipruritic compositions contain antihistaminic molecules (fexofenadine, mizolastine, isothipendyl) for ingesting or topical application, but also local anesthetics, antiseptics or even corticosteroids (hydrocortisone). However, some of these compounds may be aggressive to the skin (especially corticosteroids) and / or have undesirable side effects. So we are looking more and more to find products with a significant biochemical effect against the development of pruritus without being aggressive to the skin. The release of TSLP (Thymic Stromal Lymphopoietin) by the cells of the body is one of the ways of developing pruritus. Indeed, it is nowadays admitted that TSLP interleukins are transmitters of allergic reactions, and therefore of pruritus and associated cutaneous inflammation. Therefore, compounds which make it possible to reduce the release of TSLP, which may have an antiallergic and / or antipruritic effect, are actively sought.

TRPV1 is another way of developing pruritus. It is the most known receiver of the TRPV family. It is expressed by neurons and cutaneous cells (keratinocytes). It is a channel receptor allowing calcium and magnesium bivalent ions to enter the cell. TRPV1 is a nociceptive receptor sensitive to temperature, pH and vanilloid (irritant) changes such as capsaicin. Activation of TRPV1 by capsaicin induces: - a calcium influx in the cell; - the sensation of pain and itching by the release of neuropeptides; a release of cytokines inducing pruritus. In practice, TRPV1 receptors are involved in the initial phases of pruritus, when the "scraping" mentioned above has not yet had too many harmful effects. TRPV1 receptors induce the sensation of need for scratching when stimulated, and to a lesser extent pain. Compounds for decreasing the stimulation of these receptors are therefore actively sought. The CB1 and CB2 endocannabinoid receptors are yet another recently discovered pathway to treat pruritus and associated pain. These are G protein-coupled membrane receptors present in the brain, liver, kidneys, lungs and skin. CB1 and CB2 are especially present on the surface of skin cells in response to stimulation, irritation or inflammation, so as to relieve pain if endocannabinoids are present in the medium. In practice, the stimulation of these receptors corresponds to the acute phase of pruritus, when the inflammation becomes important and painful. In particular, CB1 and CB2 cannabinoid receptor agonist compounds have been found to have an antipruritic effect in orally administered compositions, and compounds having antagonist activity of these receptors effectively block the antipruritic effect of the agonist compounds (EP2130820 ).

However, the reference molecules in the fight against pruritus are still antihistamines or corticosteroids. Most antipruritic compounds act only on a single pruritus-triggering pathway and thus must be supplemented in complex, often irritating or even harmful compositions, including those comprising an antiseptic, a local anesthetic, several antipruritic drugs, a corticosteroid, and so on. For the moment, there is little or no antipruritic treatment and associated pain through original biochemical pathways and no unpleasant side effects. The present invention proposes to solve this problem with cosmetic and / or dermatological and / or therapeutic compositions comprising, as an active ingredient, mineral water, and without any unpleasant side effect. The Applicant has discovered in a completely fortuitous and surprising manner that a composition comprising as an active ingredient a mineral water rich in trace elements and mineral salts makes it possible both to reduce the release of TSLP and to regulate the TRPV1 receptor and endocannabinoid receptors CB1 and CB2. The subject of the invention is therefore a 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 of 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 reduction of the release of TSLP and / or in the regulation of the TRPV1 receptor and of the receptors cannabinoids CB1 and CB2.

According to another 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 yet another characteristic of the invention, the mineral water is in a mass proportion of between 1% and 100%. According to 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 10%. According to another characteristic of the invention, the mineral water is in a mass proportion of 30%. According to yet another characteristic of the invention, the mineral water is in a mass proportion of 50%. According to another characteristic of the invention, the mineral water is constituted by Uriage Thermal Water. According to yet another characteristic of the invention, calcium, magnesium and sodium and / or their salts and / or derivatives are present in mineral water at respective concentrations of 42.7 mg / L, 21.2 mg / L and 4.8 mg / L. According to another characteristic of the invention, calcium and / or its salts and / or 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 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 characteristic of the invention, the composition according to the invention further comprises, as active ingredient, omega 6 borage amide in a mass proportion of between 0.001% and 10%.

According to another characteristic of the invention, the composition according to the invention is used to soothe sensitive or irritated skin and / or in the treatment of pruritus and / or inflammation and / or pain and / or reactions. allergic skin or mucous membranes. Graph 1 represents the evaluation of the effect of ETU with TNF-α on the immunolabeling of CB1. Figure 2 represents the evaluation of the effect of ETU with TNF-α on CB2 immunostaining. Chart 3 represents the evaluation of the effect of ETU with TNF-a on immunostaining of TRPV1. Chart 4 represents the evaluation of the effect of TNF-free ETU on CB1 immunostaining. Figure 5 represents the evaluation of the effect of ETU without TNF-α on CB2 immunostaining. Chart 6 represents the evaluation of the effect of ETU without TNF-α on immunostaining of TRPV1. In all the graphs, the ordinate represents the amount of fluorescence emitted quantified by the computer analyzer. This quantity is expressed in an arbitrary unit of fluorescence specific to the analyzer. A first advantage of the invention is to act against the allergic reactions of the cells inducing inflammation and especially pruritus by decreasing the release of TSLP by the body. A second advantage of this invention is to have a significant effect against the initiation phase of pruritus and acute phase respectively by decreasing the stimulation on the one hand of the TRPV1 receptor and on the other by CB1 and CB2 endocannabinoid receptors. . A third advantage of the invention is the external or internal treatment of allergic reactions and inflammation of the mucous membranes or skin. A final advantage of the invention is its total safety for the human body.

By mineral water rich in trace elements and mineral salts is meant a mineral water comprising at least, in relation to common water (tap or even bottle), high proportions including 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 11 000 mg / L -Calcium: 600 mg / L -Magnesium: 125 mg / L -Potassium: 45.5 mg / L -Sodium: 2360 mg / L -Sulfates: 2860 mg / L -Chlorides: 3500 mg / L -Bicarbonates: 390 mg / L -Silicon: 42 mg / L -Zn: 160 μg / L -Mn: 154 μg / L -Cu: 75 μg / L-Fe: 15 μg / L Uriage Thermal Water or ETU is recognized as one of the mineralized thermal waters most balanced 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: - limit the triggering of the pruritus-related inflammatory reaction generated by the allergens through the TSLP (Thymic Stromal Lymphopoietin) pathway; - Limit the onset of pruritus and related pain by reducing the stimulation of a major TRPV (Transient Receptor Potential Vanilloid) receptor, TRPV1, and by regulating CB1 and CB2 cannabinoid receptors.

Thus, a cosmetic and / or dermatological and / or therapeutic composition comprising ETU allows the treatment of the mucous membranes and pruriginous and / or inflamed skins 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. It is the same when the ETU is applied internally to the body using a medical device, for example a medical spray device intended to introduce the composition according to the invention into the human nostrils such that a nasal spray. The composition according to the invention can also be very well integrated in intended single-dose units or in nostrils or in 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. It is quite possible to combine the mineral water included in the composition according to the invention. the invention with other active ingredients effective in the treatment of inflamed, irritated and / or itchy skin. There may be mentioned omega 6 borage amide whose INCI name is "Borage seed oil aminopropanediol amides", of plant origin and obtained by enzymatic biotechnology. The omega 6 borage amide has a significant action from a mass concentration equal to or greater than 0.001% and preferably less than 10%. This active ingredient makes it possible to treat pruritus and afferent affections by a biochemical pathway different from that of the mineral waters according to the invention, by promoting the formation of natural molecules participating in the resolution of cutaneous inflammations and by inhibiting certain pro-inflammatory molecules. Thus, it is possible to combat pruritus and its effects across a wide range of simultaneous biochemical processes. Finally, like the mineral waters according to the invention, omega 6 borage amide has no toxicity to humans.

In the following test, the authors of the present invention evaluated the effect of ETU, in a model of reconstructed human epidermis, on the release of TSLP (Thymic Stromal Lymphopoietin) induced by the combination of IL-1. 1a and Poly (I: C). IL-1a (IL is the abbreviation for interleukin) is a cytokine released by keratinocytes in case of lesions or defects in the skin barrier. The treatment of the epidermis with IL-1 1 thus leads to a weakening of the barrier function of the keratinocytes. Poly (I: C) is an allergen that will stimulate keratinocytes whose barrier function has been weakened. Thus, the double antigenic stimulation IL-1a and Poly (I: C) causes the expression and early release of the cytokine TSLP which is responsible for the activation and migration of dendritic cells via the heterodimeric receptor TSLP-R / IL-7a. Material and methods Biological model Epiderms: 15 reconstructed human epidermis (RHE) 10-day BIOalternatives Lot # 01015-269. The RHE model is derived from the method of Poumay et al., A simple reconstructed human epidermis: Arch Dermatol Res., 2004 Oct, 296 (5): 203-11 .

Culture conditions: 37 ° C, 5% CO2. Test medium: BlOalternatives maintenance medium. When the ETU is not 100%, it is diluted in water in the cell.

Test compound Uriage Thermal Water (ETU) - Liquid stored at room temperature - Molecular weight: 1.01. Application: Topical at 100 mg / cm2 or 50 μl / epidermis. Concentrations tested: 10, 30 and 100%.

Culture and treatment The RHE were treated or not (control), topically with the ETU and pre-incubated for 24 hours. Treatment with ETU was then renewed and the epidermis re-incubated for 30 minutes. The RHEs were then stimulated or not (non-stimulated control) with the inducer: Poly (I: C) at 10 μg / ml + IL-la at 10 ng / ml in the presence or absence (stimulated control) of the compound at 1 test, then the epidermis was incubated for 24 hours. The experimental conditions were carried out 3 times each. At the end of the incubation, culture media were collected for TSLP (Thymic Stromal Lymphopoeitin) assay. Quantification of TSLP by ELISA (enzyme-linked immunosorbent assay) At the end of the incubation, the amount of TSLP present in the culture media was measured using an ELISA assay kit according to the following supplier specifications: Reference: R & D systems.

ELISA kit: TSLP. Lower detection limit: 31.3 pg / ml. Upper limit of detection: 2000 pg / ml. The results are expressed in μg / ml of TSLP and in percentage of the secretion / release relative to the stimulated control. Data Processing Intergroup comparisons were performed using the unpaired bilateral Student T test. Statistical analyzes can be interpreted if n> _5; for n <5, the calculated data are provided for information purposes only. Formulas used in this report: Inhibition (%) = 100 * (Mean Stimulated Control - Value) / 5 (Mean Stimulated Control - Mean Basal Control). Standard error of the mean: esm = standard deviation (Sd) hin Table 1: TSLP / ETU test results Treatment Basic data Normalized data Condition Composition Average TSLP (ng / ml) Esm% Stimulated control% inhibition tested (pg / ml ) Unstimulated condition Control <31 0 <31 100 Condition Control 219 19 100 0 stimulated: Poly (I: C) 10 μg / ml + IL-10 ng / ml ETU 10% (mass) 224 18 102 -3 ETU 30% (mass) 217 2 99 1 100% ETU (mass) 159 6 73 32 Interpretation of results Consistently, under unstimulated conditions, no basal release of TSLP was observed. Treatment of the epidermis with the pro-inflammatory Poly (I: C) + IL-1α mixture markedly stimulated the release of TSLP. At concentrations of 10% and 30%, ETU has no significant effect on Poly (I: C) + IL-11-induced TSLP production. On the other hand, the ETU tested pure (100%) in topical application significantly inhibited the production of TSLP (32% inhibition), which makes it possible to limit the triggering of the inflammatory reaction generated by allergens and therefore of pruritus. .

The authors of the present invention have also evaluated by immunostaining the effects of Uriage Thermal Water on the expression of endocannabinoid receptors (CB1 and CB2) and on the expression of the TRPV1 receptor in normal human keratinocytes, stimulated or not with TNF-a. TNF-α (Tumor Necrosis Factor a) is a cytokine significantly involved in systemic inflammation and in the acute phase reaction. If a compound removes part of the CB1 and CB2 from the surface of the cells is that it reduces the stimulation / irritation / inflammation of the skin, the cell thus less need relief. The immunolabeling protocol is as follows: Seeding of the cells 30 days Pretreatment with the products 35/6 hours Stimulation with TNF-a 10 ng / ml hours - Immunolabeling CB1, CB2 and TRPV1 Normal human keratinocytes (KHN - primocultures) are seeded at the density of 20,000 cells / well (KSFM medium - Gibco® Invitrogen) in 8-well LabTeks II (Nunc). LabTeks are placed in a humid oven (37 ° C and 5% 002) for 5 days. Uriage Thermal Water: - Lot n °: 107011 - Storage: Ambient temperature - Form: 100% solution The ETU is tested at concentrations of 10% and 3%. Dilution is done with water from the cell medium. The cells are placed in the presence of the ETU for 6 hours. Wells remain untreated to serve as control conditions. The cells are then stimulated with TNF-a at the final concentration of 10 ng / ml in the presence of the products at first (graphs 1 to 3). Control wells remain unstimulated. Each condition is evaluated in duplicate. In a second step, the effect of ETU is evaluated without stimulation to TNF-a (Charts 4 to 6). Each condition is evaluated in duplicate. After 24h stimulation, the cells are rinsed, fixed in 4% formaldehyde and permeabilized with 0.1% Triton X100. Non-specific sites are saturated with serum (BSA 1%). The cells are incubated in the presence of the primary antibody for 1H (anti-CB1, anti-CB2 and antiTRPV1), then rinsed. A second incubation allows the signal to be revelated with a secondary antibody coupled to a fluorochrome. The labeling of the cell nuclei is carried out with the DAPI dye (4'6'-Diamidino-2-phenylindol dihydrochloride).

Results and conclusion The results are shown in graphs 1 to 6, the ordinate representing the quantity of fluorescence emitted quantified by the computer analyzer. This quantity is expressed in an arbitrary unit of fluorescence specific to the analyzer. . It can be seen that immunolabeling reveals the decrease in the expression of the CB1, CB2 and TRPV1 receptors when the keratinocytes are treated beforehand with the 3% or 10% ETU, and that one is in inflammatory conditions ( with TNF-a stimulation) or not. The ETU thus contributes to the reduction of pruritus and pain related to this problem via the regulation of these receptors. Examples of compositions comprising ETU (EU INCI name: "Uriage Thermal Spring Water") according to the invention: Example 1: Cleaning oil INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 5 Borage seed oil aminopropanediol amides 0 , 01 Glycerin 19 Hydrogenated starch hydrolysate 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: Cream hands INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 10 Borage seed oil aminopropane diol amides 0.1 Glycerin 3 Phenoxyethanol 0.5 Chlorphenesin 0.2 Acrylates / C10-30 alkyl acrylate crosspolymer 0.17 Glyceryl stearate PEG-100 stearate e 3 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 30 Borage seed oil amides aminopropanediol 0.006 Butyrospermum parkll (shea butter) 5 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 aminopropanediol esters 0.05 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 amides aminopropanediol 1 Perfume 0,2 C itric acid 0.028 Phenoxyethanol 0.7 Chlorphenesin 0.3 Glycerin 7 Xanthan gum 0.3 Glyceryl stearate PEG-100 stearate 1,2 Cetearyl isononanoate 5 Propylheptyl caprylate 3 Pentaerythrityl distearate 2 Cetyl alcohol 0.7 Cetearyl alcohol 2 Glyceryl stearate 1.8 Butyrospermum parkll (shea butter) 5 Tocopheryl acetate 0.5 Dimethicone 1 Cetearyl alcohol cetearyl glucoside 2 o-cymen-5-ol 0.1 Butylene glycol 3 Example 5: oleo-thermal liniment INCI name EU% (mass) Uriage Thermal Spring Water 60 Helianthis anuus seed oil 30 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 are not 5 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. . The active ingredients in the compositions are used at the same concentrations as in previous in vitro studies. Their activity will be equivalent because most pruriginous skin has an impaired skin barrier and penetration is facilitated. The assets can thus be easily in contact with the underlying cell layers, consisting of living epidermal cells. 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.

Claims (14)

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 cosmetically and / or dermatologically and / or therapeutically acceptable compounds for use in decreasing TSLP release and / or in regulating TRPV1 receptor and CB1 and CB2 cannabinoid receptors. 2. Composition according to claim 1, characterized in that the calcium and magnesium and / or the salts and / or the derivatives thereof present in the mineral water are in a weight ratio Ca / Mg of between 1 and 10. 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%. 4. Composition according to one of the preceding claims, characterized in that the mineral water is in a mass proportion of 5%. 30 5. Composition according to one of the preceding claims, characterized in that the mineral water is in a mass proportion of 10%. 6. Composition according to one of the preceding claims, characterized in that the mineral water is in a mass proportion of 30%. 7. Composition according to one of the preceding claims, characterized in that the mineral water is in a mass proportion of 50%. 8. Composition according to one of the preceding claims, characterized in that the mineral water is constituted by Uriage Thermal Water. 9. Composition according to one of claims 1 to 5, characterized in that the calcium, magnesium and sodium and / or their salts and / or derivatives are present in the mineral water in concentrations of 42.7 mg respectively / L, 21.2 mg / L and 4.8 mg / L. 10. Composition according to one of claims 1 to 5, 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. 11. Composition according to one of claims 1 to 5, characterized in that calcium, magnesium, potassium and sodium and / or their salts and / or derivatives are present in the mineral water in concentrations of 236 respectively. mg / L, 28.1 mg / L, 29.9 mg / L and 982 mg / L. 12. Composition according to one of the preceding claims characterized in that it is integrated into one or more medical devices: a nasal spray, nasal unidoses, and ocular unidoses. 13. Composition according to one of the preceding claims, characterized in that it further comprises as active ingredient omega 6 borage amide in a mass proportion of between 0.001% and 10%. 14. Composition according to one of the preceding claims for its use for soothing sensitive or irritated skin and / or in the treatment of pruritus and / or inflammation and / or pain and / or allergic reactions of the skin. skin or mucous membranes.