Combination of Astragalin and Miquélianin to inhibit the activity of S aureus lipase.

Abstract

The invention relates to a composition comprising Astragalin (K) and Miquélianin (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5. The invention also relates to the use of a composition according to the invention, in particular to prevent and / or reduce the virulence of S. aureus, and / or to prevent and / or reduce its uncomfortable and / or unsightly manifestations on healthy skin and / or healthy mucous membranes, and / or to treat skin and / or mucous membrane infections caused by S. aureus.

Description

Title of the invention: Combination of Astragalin and Miquélianine to inhibit the activity of S aureus lipase. technical field

[0001] The invention relates to the field of dermatological or cosmetic compositions, and in particular to compositions for preventing and / or reducing the virulence of S. aureus and / or for preventing and / or reducing its uncomfortable and / or unsightly manifestations on healthy skin and / or mucous membranes and / or for treating skin and / or mucous membrane infections caused by S. aureus. The invention relates in particular to a combination of two compounds, kampferol-3-O-glucoside and quercetin-3-O-glucuronide, having a synergistic effect, notably for inhibiting the activity of S. aureus lipase. Technological background

[0002] Dermatitis is a superficial skin inflammation characterized by vesicles, erythema, edema, oozing, scaly or crusty lesions, and intense itching. There are different types of dermatitis: contact dermatitis, which can be caused by irritants with which the skin comes into contact or by non-irritating substances to which the individual is allergic; atopic dermatitis, a chronic disease characterized by severe itching; and seborrheic dermatitis, a scaly disease that mainly affects the face and scalp.

[0003] Dermatitis is notably induced by an imbalance of the skin microbiota, which involves a reduction in bacterial diversity and significant colonization by the opportunistic bacterium Staphylococcus aureus (S. aureus). S. aureus lipase (SAL), also known as glycerol ester hydrolase, hydrolyzes sebum triglycerides into glycerol and free fatty acids. Some free fatty acids serve as nutrients and thus promote the growth of S. aureus. Furthermore, other free fatty acids, such as oleic acid, disrupt the skin's barrier function, making it more permeable to allergens and pollutants. Oleic acid is also an irritant to epidermal cells and can trigger the secretion of inflammatory cytokines such as interleukin-1 alpha.

[0004] Inhibition of S aureus lipase (SAL) activity therefore makes it possible to treat skin infections caused by S aureus, and in particular dermatitis.

[0005] The lipase activity of S. aureus does not necessarily cause pathologies of the skin and / or mucous membranes. On healthy skin, it can also be responsible for a number of uncomfortable and / or unsightly manifestations. Examples include dry skin and / or mucous membranes, uneven skin tone and / or mucous membranes, particularly with the appearance of redness, sensations of tightness, tingling, prickling, prickling, tension, and / or itching of the skin and / or mucous membranes, a rough texture of the skin and / or mucous membranes, and / or a loss of softness to the touch. These uncomfortable and / or unsightly symptoms are exacerbated in the case of sensitive, sensitized, fragile, weakened, dry, and / or atopic-prone skin and / or mucous membranes.

[0006] There is therefore a constant need to identify inhibitors of S. aureus lipase activity (SAL) as alternatives to those already described and marketed, particularly for their use in the treatment of pathologies caused by S. aureus, especially dermatitis, but also to improve the appearance and / or comfort of sensitive, sensitized, fragile, weakened, dry, and / or atopic-prone skin and / or mucous membranes.

[0007] Miquelianin (Q), also known as quercetin-3-O-glucuronide, is a flavonol with the formula (Q) shown below ([Chem 1]). Miquelianin is particularly known for its antidiabetic, antioxidant, and antidepressant properties. This molecule is notably present in the following plants: Castanea saliva (leaves, flowers), Hypericum perforatum, Nelumbo nucifera, Gaultheria miqueliana, Adiantum capillus veneris, Phaseolus vulgaris, Achillea millefolium, Arnica montana, Centella asiatica, Foeniculum vulgare, Rubus idaeus, Myrothamnus flabellifolius, Oenothera biennis, Vitis vinifera, and strawberry cultivars.

[0008] [Chem.l] OH OH (Q)

[0009] Astragalin (K), also known as kampferol-3-O-glucoside, is a flavonol with the formula (K) shown below ([Chem 2]). This molecule is found in particular in the following plants: Castanea saliva, Astragalus sp., and Vitis vinifera. Astragalin (K) is known as an anti-inflammatory, antioxidant, anti-ROS agent, and as a skin protectant against UV radiation and stress (JP07118151; US7211567; and WO2004 / 037184).

[0010] [Chem.2]

[0011] A combination of Astragalin with Quercetin in a 1:1 ratio is disclosed in Korean patent application KR20120121684, for its activity on atopic dermatitis, irritation, and inflammation. This combination is notably used for its activity against itching. Summary of the invention

[0012] In this context, the inventors discovered that the combination of two compounds, Astragaline (K) and Miquélianine (Q), significantly inhibits the virulence of S. aureus, in particular the activity of S. aureus lipase (SAL). This inhibition is significantly greater than the inhibition induced by each compound taken individually. The inventors thus discovered a synergistic effect of the combination of Astragaline and Miquélianine in inhibiting SAL activity and therefore reducing the virulence of S. aureus.

[0013] The inventors have notably discovered that this combination can be used as a cosmetic agent, particularly to improve the appearance and / or comfort of healthy skin and / or mucous membranes, and / or for the cosmetic care of healthy skin and / or mucous membranes, particularly sensitive, sensitized, fragile, weakened, dry, and / or healthy skin prone to atopic dermatitis. This combination, through its properties that inhibit the activity of S. aureus, helps to prevent and / or inhibit the degradation of the skin barrier and thus limit insensible water loss. It is therefore also useful as a soothing agent for the skin and / or mucous membranes and / or as a moisturizing agent for the skin and / or mucous membranes. This combination can also be used as an active ingredient in a pharmaceutical or dermatological composition, particularly as an anti-inflammatory agent and an antibacterial agent, insofar as it inhibits the virulence of S.aureus and / or, in the treatment and / or prevention of skin infections caused by S. aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, particularly diaper rash, and / or in the prevention and / or pharmaceutical, particularly dermatological, treatment of pathologies related to reactive and / or atopic skin. This combination is useful. for the dermatological care of atopic and / or reactive skin and / or the skin of infants to prevent diaper rash.

[0014] The inventors also discovered that better synergy is obtained with a mass ratio K / Q between 1 / 1.5 and 1 / 3.5.

[0015] The invention therefore relates to a composition comprising a combination of Astragalin (K) and Miquelianin (Q) characterized in that the mass ratio K / Q is between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3.

[0016] The composition according to the invention is advantageously intended for topical administration.

[0017] The composition according to the invention is advantageously characterized in that the combination of Astragaline (K) and Miquelianine (Q) is included in a plant extract, preferably an extract of Castanea saliva leaves, enriched in Astragaline (K) and Miquelianine (Q) so as to have a K / Q mass ratio between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3.

[0018] Advantageously, the extract is obtained by extraction in water, preferably at a temperature between 70 and 90 °C, for example for 30 minutes to 2 hours.

[0019] Advantageously, the extract comprises the combination of Astragalin (K) and Miquélianin (Q) in an amount between 0.001 g / 100 ml of extract and 1 g / 100 ml of extract, preferably between 0.01 g / 100 ml of extract and 0.1 g / 100 ml of extract, in particular between 0.02 g / 100 ml of extract and 0.03 g / 100 ml.

[0020] The composition according to the invention advantageously comprises a content of the combination of Astragalin (K) and Miquélianin (Q) of between 0.4 and 0.6% by mass relative to the total mass of the composition.

[0021] The invention also relates to a cosmetic composition comprising a composition according to the invention and a cosmetically acceptable excipient.

[0022] The invention also relates to the non-therapeutic cosmetic use of a cosmetic composition according to the invention, to prevent and / or reduce uncomfortable and / or unsightly manifestations on the skin and / or mucous membranes of the virulence of S. aureus and / or for the cosmetic treatment of healthy sensitive skin and / or mucous membranes, healthy sensitized skin and / or mucous membranes, healthy fragile and / or weakened skin and / or mucous membranes, healthy dry skin and / or mucous membranes, and healthy skin and / or mucous membranes with atopic tendencies, and / or as a soothing agent or moisturizing agent.

[0023] The invention also relates to a cosmetic treatment method characterized in that it comprises the topical application to at least one area of ​​healthy skin and / or healthy mucous membranes of a cosmetic composition according to the invention, for the cosmetic treatment of sensitive healthy skin and / or healthy mucous membranes, healthy skin and / or healthy sensitized mucous membranes, healthy skin and / or healthy mucous membranes that are fragile and / or weakened, healthy dry skin and / or mucous membranes, and healthy skin and / or healthy mucous membranes with atopic tendencies, and / or as a soothing or moisturizing agent.

[0024] The invention also relates to a pharmaceutical and / or dermatological composition comprising a composition according to the invention and a pharmaceutically and / or dermatologically acceptable excipient.

[0025] The invention also relates to a pharmaceutical and / or dermatological composition according to the invention, for use as an anti-inflammatory agent, antibacterial agent and / or in the treatment and / or prevention of skin and / or mucous membrane infections associated with S. aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, in particular diaper rash, and / or in the prevention and / or pharmaceutical treatment, particularly dermatological treatment, of pathologies related to reactive and / or atopic skin. Detailed description

[0026] For the purposes of the present invention, "cosmetic use" and / or "cosmetic composition" means a non-pharmaceutical use and / or composition, that is to say, one which is not intended for therapeutic use and is applied to a part of the body said to be healthy, in particular to an area of ​​skin said to be healthy.

[0027] For the purposes of the present invention, "healthy skin and / or mucous membrane" means an area of ​​human skin and / or mucous membrane on which the agent or composition according to the invention is applied and which is said to be "non-pathological" by a dermatologist, that is to say, not showing any infection, scar, disease or skin condition such as candidiasis, impetigo, psoriasis, eczema, inflammation, ichthyosis, acne or dermatitis, or any wounds or injuries.

[0028] For the purposes of this invention, "skin" means the skin of all or part of the body, in particular human, preferably chosen from the legs, feet, armpits, hands, thighs, belly, décolleté, neck, arms, torso, back, face and / or scalp, advantageously the décolleté and / or face, further advantageously the face.

[0029] For the purposes of the present invention, "mucous membrane(s)" means the nasal, ocular, vaginal, urogenital and / or oral mucous membrane, in particular the labial and / or gingival mucous membrane, preferably the nasal, urogenital and / or oral mucous membranes, and even more preferably the nasal mucous membrane.

[0030] For the purposes of the present invention, "prevent and / or decrease" means to prevent the increase and / or reduce compared to a measurement taken in the absence of treatment, in particular cosmetic, dermatological or pharmaceutical (placebo).

[0031] For the purposes of the present invention, "virulence of S. aureus" means the expression of virulence factors of S. aureus, in particular the adhesion capacity of S. aureus, the lipase activity of S. aureus, the hyaluronidase of S. aureus, the activation of plasminogen to plasmin by S. aureus, the formation of the biofilm of S. aureus, preferably the lipase activity of S. aureus.

[0032] For the purposes of the present invention, "inhibition of S. aureus lipase activity" means a decrease in S. aureus lipase activity of at least 10%, preferably at least 20%, and even more preferably at least 30%, compared to S. aureus lipase activity measured in the absence of treatment, particularly cosmetic, dermatological, or pharmaceutical (placebo). Advantageously, the inhibition of S. aureus lipase activity is measured according to the protocol described in Example 2 or 3.

[0033] For the purposes of the present invention, "physiologically acceptable excipient" means an excipient suitable for topical application for cosmetic, pharmaceutical or dermatological use, non-toxic, non-irritating to the skin, not inducing an allergic response, and not chemically unstable.

[0034] Generally speaking, "sensitive skin and / or mucous membranes" can be defined as healthy skin and / or mucous membranes that, by their nature, have a very low tolerance for aggressive agents, particularly environmental agents such as pollutants, climatic factors (wind, cold, heat), UV exposure, emotional factors such as stress, and / or chemical agents (heavy metals, detergents, compounds contained in cosmetic treatments such as perfumes, preservatives, alcohols, pH adjusters, AHAs, or dermatological agents such as retinoic acid (vitamin A acid)), and / or aggressive conditions such as perspiration and mechanical aggressions such as hair removal, shaving, friction, and even water, especially hard water. Sensitive skin is not pathological, unlike allergic skin.However, they can react to aggressive agents and / or conditions with unsightly and / or uncomfortable cutaneous and / or mucosal manifestations such as skin and / or mucosal dryness, loss of evenness in skin tone and / or mucous membranes, particularly through the appearance of redness, sensations of tightness, tingling, prickling, prickling, tension and / or itching, a rough texture of the skin and / or mucous membranes and / or a loss of softness to the touch. Thus, the "sensitive skin" characteristic can be assessed by the individual. either himself with subjective skin sensations or by the dermatologist with objective skin reactions.

[0035] Unsightly and / or uncomfortable symptoms may be generalized to the entire body, but most of the time they can have well-defined locations such as, for example, the scalp, face, skin folds, buttocks in infants, etc. They may therefore involve sensitive areas of skin and / or mucous membranes.

[0036] Similarly, "sensitized skin and / or mucous membranes" are healthy skin and / or mucous membranes made momentarily sensitive and therefore not pathological as such.

[0037] "Fragile or weakened skin and / or mucous membranes (i.e., temporarily made fragile)" refers to healthy skin and / or mucous membranes whose barrier function is weakened. This condition may be related to the individual's health and / or age, with the elderly and infants, for example, having fragile skin. This condition may also result from chemical or physical aggression (abrasion, friction, cuts).

[0038] “Atopic-prone skin and / or mucous membranes” are healthy skin and / or mucous membranes that are extremely fragile and / or weakened, with increased permeability due to a weakened barrier function, and which are genetically predisposed to develop, under the influence of multiple intrinsic and extrinsic factors, into a pathological state, namely atopic dermatitis. Thus, the “atopic-prone skin” characteristic can be assessed by the individual themselves through subjective skin sensations or by the dermatologist through objective skin reactions.

[0039] The uncomfortable and / or unsightly manifestations of sensitized, fragile and / or weakened skin and / or mucous membranes are the same as for sensitive skin and / or mucous membranes, without these manifestations and / or skin conditions being related to the prevention and / or treatment of a pathology.

[0040] “Reactive skin and / or mucous membrane”, otherwise called intolerant, irritable or allergic, is skin and / or mucous membrane whose tolerance threshold has decreased and which reacts excessively.

[0041] “Atopic skin and / or mucous membrane” is skin and / or mucous membrane affected by the pathology atopic dermatitis.

[0042] The characteristics "reactive skin and / or mucous membrane" and "atopic skin and / or mucous membrane" can be assessed by the dermatologist with objective skin reactions.

[0043] For the purposes of the present invention, "unsightly and / or uncomfortable manifestations" of the virulence of S. aureus, in particular of the lipase activity of S. aureus, include dryness of the skin and / or mucous membranes, a loss of homogeneity of skin tone and / or mucous membranes, notably through the appearance of redness, sensations of tightness, overheating, heat, tingling, prickling, Tension and / or itching, a rough appearance of the skin and / or mucous membranes, and / or a loss of softness to the touch of the skin and / or mucous membranes. The unsightly and / or uncomfortable manifestations of S. aureus virulence, in particular the lipase activity of S. aureus, are therefore found on healthy skin and / or mucous membranes, preferentially on sensitive, sensitized, fragile, weakened, dry, and / or atopic-prone skin and / or mucous membranes.

[0044] Composition according to the invention

[0045] The present invention relates to a composition, in particular a cosmetic, pharmaceutical, and in particular dermatological composition, comprising Astragalin (K) and Miquélianin (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5. The inventors have identified that, in a completely surprising way, these two compounds in this particular proportion exhibit a synergistic effect.

[0046] The composition according to the invention may be a composition intended for topical administration. Advantageously, the composition according to the invention is a composition for topical administration. "Topical route" means the direct local application and / or spraying of the composition onto the surface of the skin and / or mucous membranes. Thus, the composition may be applied topically to all or part of the skin of the body, advantageously selected from the legs, feet, armpits, hands, thighs, abdomen, décolleté, neck, arms, torso, back, face including the forehead, cheeks, nose, temples, T-zone (forehead, nose, and chin), and / or scalp, and / or to all or part of the mucous membranes.

[0047] In the context of the invention, the combination of Astragalin (K) and Miquélianin (Q) is used as an active agent in the composition, in particular as a cosmetic, pharmaceutical or dermatological active agent.

[0048] Advantageously, the composition according to the invention comprises Astragaline (K) and Miquelianine (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1. The combination of Astragaline (K) and Miquelianine (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, has a synergistic effect on the inhibition of S. aureus lipase activity. For the purposes of the invention, "synergy effect" means a decrease in S. aureus lipase activity of at least 3%, advantageously at least 5%, and even more advantageously at least 7%, greater than the decrease in S. aureus lipase activity measured in the presence of Astragalin (K) or Miquélianin (Q) alone. In a very particular embodiment, the synergistic effect is such that the decrease in S. aureus lipase activity...aureus with the combination of Astragaline (K) and Miquélianine (Q) is greater than the sum of the decreases in S. aureus lipase activity with Astragaline (K) alone and with Miquélianine. (Q) alone. The activity of S. aureus lipase can be tested according to the protocol indicated in example 2 or 3.

[0049] The present invention therefore relates to a composition comprising a combination of Astragalin (K) and Miquelianin (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1, said composition advantageously comprising an Astragalin (K) content of 1 x 10⁶% to 0.1%, preferably 1 x 10⁵% to 0.1%, by mass relative to the total mass of the composition, and advantageously a Miquelianin (Q) content at a concentration of 1 x 10⁶% to 2.3 x 10⁻²%, preferably 1 x 10⁵% to 2.3 x 10⁻²%, by mass relative to the total mass composition.

[0050] Advantageously, when the molecules are contained in a plant extract, in particular Castanea saliva, the content of flavanol glycosides in said extract is equal to or greater than at least 20 ppm.

[0051] In an advantageous embodiment, the composition according to the invention further comprises a physiologically acceptable excipient, in particular cosmetically, pharmaceutically or dermatologically acceptable.

[0052] According to one embodiment, Astragalin (K) and Miquélianin (Q) are used as purified molecules, in particular without being associated with other flavonols. Specifically, they are not added in the form of a plant extract.

[0053] In an alternative embodiment of the invention, Astragaline (K) and Miquélianine (Q) are obtained from a plant extract. "Plant extract" means an extract of all or part of a plant selected from the aerial parts, leaves, flowers, petals, stems, fruit, fruit peel, seeds, roots, rhizomes, and any combination thereof.

[0054] In one embodiment, Astragalin (K) and Miquelianin (Q) are provided in the composition in the form of a purified extract or an extract enriched with Astragalin (K) and Miquelianin (Q). In one aspect, the two molecules are obtained from an extract of a single plant. In another aspect, the two molecules are obtained from two extracts of different plants.

[0055] When the two molecules are obtained from two different plant extracts, Michelianin (Q) can be purified from an extract of all or part of a plant including, such as a plant chosen from: Castanea sativa (leaves, flowers), Hypericum perforatum, Nelumbo nucifera, Gaultheria miqueliana, Adiantum capillus veneris, Phaseolus vulgaris, Achillea millefolium, Arnica montana, Centella asiatica, Foeniculum vulgare, Rubus idaeus, Myrothamnus flabellifolius, Oenothera biennis, Vitis vinifera, and Strawberry cultivars; and / 'Astragalin (K) can be purified from an extract of all or part of a plant including, such as a plant chosen from: Castanea sativa (leaves), Myrothamnus flabellifolius, Astragalus sp and Vitis vinifera.

[0056] The plant variety and / or the plant part chosen will be selected beforehand for its Astragalin (K) and Miquelianin (Q) content, and the extraction will be carried out according to conventional methods to promote obtaining the desired mass ratio of Astragalin (K) to Miquelianin (Q), in particular as described below. In a particular embodiment, when the plant extract is an extract of Castanea sativa, in particular of Castanea sativa leaves, the extract originates from France, and more specifically from the Cher or Ardèche regions.

[0057] According to a preferred embodiment, Astragalin (K) and Miquelianin (Q) are provided in the composition in the form of an extract enriched in Astragalin (K) and Miquelianin (Q) obtained from a single plant, the extract preferably being an extract of Castanea sativa, in particular an extract of the aerial parts of Castanea sativa, more particularly of Castanea sativa leaves. In a particular embodiment, the extract is enriched in Astragalin (K) and Miquelianin (Q) so as to have a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1.

[0058] The plant extract, and in particular the extract of Castanea sativa leaves, is obtained by any extraction method known to those skilled in the art, chosen from maceration, hot decoction, grinding (including ultrasonic grinding), grinding with a mixer, or the extract may be obtained by extraction in water under subcritical or supercritical conditions (carbon dioxide). Preferably, the extraction is carried out by maceration or by solvent extraction, in particular in water.

[0059] The extraction can be carried out from dry or fresh material, advantageously dry, in quantities of 0.1% to 20% by mass, advantageously from 1% to 10%, very advantageously from 5% to 10%, and even more advantageously from 10% by mass relative to the total mass of the material and the extraction solvent.

[0060] The extraction can be carried out at a temperature ranging from 4°C to 300°C, including ambient temperature, i.e. a temperature of 18°C ​​to 25°C. In a preferred embodiment of the invention, the extraction will be carried out at a temperature of 60°C to 90°C, preferably from 70°C to 90°C, preferably from 70°C to 85°C, and even more preferably at a temperature of 80°C.

[0061] In an alternative embodiment of the invention, the extraction will be carried out at a temperature of 4°C to 25°C, more preferably from 4°C to 20°C, more advantageously at room temperature, i.e. between 18°C ​​and 25°C.

[0062] In yet another alternative embodiment of the invention, the extraction will be carried out in water under subcritical conditions, at a temperature ranging from 100°C to 300°C, advantageously from 120°C to 250°C, and further advantageously at 120°C. The extraction may be carried out at a single given temperature or at successive increasing temperatures. In an advantageous embodiment of the invention, the extraction will be carried out at a single temperature of 120°C. In an alternative embodiment, it will be conducted along a gradient of three increasing temperatures between 100°C and 200°C, such as 120°C, 140°C then 160°C or 110°C, 130°C then 150°C, or even 120°C, 145°C then 170°C.

[0063] Extraction under "subcritical conditions" means extraction in the presence of water, under temperature conditions above 100°C and pressure below 221 bars, such that the water remains in a liquid state but has a viscosity and surface tension lower than that of water at room temperature, increasing its dielectric constant.

[0064] Thus, the extraction pressure will be between 150 bars and 250 bars, preferably between 200 and 221 bars, advantageously in a pressure extraction autoclave.

[0065] Regardless of the extraction method used, the extraction can be carried out over a period of 30 minutes to 24 hours, preferably from 30 minutes to 12 hours, more preferably from 30 minutes to 5 hours, and advantageously from 30 minutes to 2 hours or from 1 hour to 2 hours. Most advantageously, the extraction will be carried out over a period of 1 hour.

[0066] In a preferred embodiment, the composition according to the invention is advantageously an extract of Castanea sativa leaves, optionally in combination with an excipient. More advantageously, the Castanea sativa leaf extract is obtained by water extraction, preferably at a temperature between 70°C and 90°C, preferably at 80°C, advantageously for a period of 30 minutes to 2 hours or from 1 hour to 2 hours, in particular 1 hour.

[0067] The extract according to the invention is therefore advantageously obtained by extraction in water as the sole solvent.

[0068] Alternatively, the extraction may be carried out in the presence of a non-ionic surfactant, preferably chosen from lauryl glucoside marketed under the name Plantacare® 1200UP by BASF or from caprylyl / capryl glucoside (Plantacare® 810 UP), preferably caprylyl / capryl glucoside (Plantacare® 810 UP). The mass concentration of the non-ionic surfactant may be between 0.5% and 5%, advantageously between 0.5% and 1%, and even more advantageously 1% by mass relative to the total mass of the extract.

[0069] The extract can be in liquid or powder form. In one embodiment of the invention, the plant extract is freeze-dried in the presence of maltodextrin present at a concentration of 70% to 90% by mass relative to the total mass of the final extract, advantageously at a concentration of 75% to 85% by mass and very advantageously at a concentration of 85% by mass of maltodextrin.

[0070] The extract according to the invention may be a purified extract of Astragalin (K) and Miquelianin (Q). In this context, the purification of Astragalin (K) and / or Miquelianin (Q) may be carried out by any suitable technique known to those skilled in the art. For example, the technique may be a chromatographic technique chosen from thin-layer chromatography or preparative high-performance liquid chromatography (HPLC). Advantageously, the purification of one or both molecules is carried out by preparative high-performance liquid chromatography (HPLC), in particular reversed-phase HPLC, most advantageously on a C18 column. Elution is carried out by a solvent gradient (for example, at 5 mL / min), advantageously in the presence of a solvent mixture, and preferably in the presence of a mixture of formic acid (1%) and acetonitrile. When the extract is in powder form, it can be resolubilized in water for purification.

[0071] Thus, in a particularly advantageous embodiment of the invention, an aqueous extract obtained in water as the sole solvent, of Castanea saliva leaves, for example as described in Example 1, comprises an Astragaline (K) content of between 0.0005 and 0.3 g per 100 ml of extract, preferably between 0.0005 and 0.0080 g per 100 ml of extract, in particular between 0.001 and 0.006 g per 100 ml of extract, and a Miquélianine (Q) content of between 0.0010 and 0.800 g per 100 ml of extract, preferably between 0.0010 and 0.0200 g per 100 ml of extract; the mass ratio K / Q being between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, especially between 1 / 2.5 and 1 / 3.3, particularly between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1.

[0072] The present invention is therefore advantageously related to an extract of Castanea sativa leaves enriched with Astragalin (K) and Miquelianin (Q), such that the extract comprises the combination of Astragalin (K) and Miquelianin (Q) in an amount between 0.001 g / 100 ml of extract and 1 g / 100 ml of extract, preferably between 0.01 g / 100 ml of extract and 0.1 g / 100 ml of extract, in particular between 0.02 g / 100 ml of extract and 0.03 g / 100 ml.

[0073] The present invention therefore advantageously relates to an extract of Castanea sativa leaves enriched with Astragalin (K) and Miquelianin (Q), such that the extract comprises an Astragalin (K) content of between 0.0005 and 0.3 g per 100 ml of extract, preferably between 0.0005 and 0.0080 g per 100 ml of extract, and a Miquelianin (Q) content between 0.0010 and 0.800 g per 100 ml of extract, preferably between 0.0010 and 0.0200 g per 100 ml of extract; the K / Q mass ratio being between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, especially between 1 / 2.5 and 1 / 3.3, particularly between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1.

[0074] In an alternative embodiment of the invention, Astragaline (K) and / or Miquelianine (Q) can be used from commercially available powders, for example from Sigma-Aldrich. In this case, Astragaline (K) and Miquelianine (Q) can be solubilized in a cosmetic ingredient at a concentration such that the K / Q mass ratio is between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, particularly between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1. Thus, in this particularly advantageous embodiment of the invention, Astragaline (K) and / or Miquelianine (Q) are added to the composition in the form of a pure product.

[0075] Astragalin (K) and Miquélianin (Q), regardless of their method of preparation, can then be physically and microbiologically stabilized by the addition of a solvent or mixture of solvents such as water, glycerol, or glycols in various proportions suitable for such stabilization. Advantageously, glycerol will be present alone or in combination with water or a glycol, advantageously in a proportion of between 40% and 95%, and preferably between 50% and 90%. Similarly, glycol will advantageously be present alone or in combination with water or glycerol, advantageously in a proportion of between 40% and 95%, and preferably between 50% and 90%. Advantageously, the solvent mixture comprises water and glycerol in a mass ratio of between 10 / 90 and 40 / 60, preferably 20 / 80.

[0076] Thus, in a particularly advantageous embodiment, the composition according to the invention comprises a combination of Astragalin (K) and Miquelianin (Q), preferably in the form of Castanea sativa leaf extract enriched with Astragalin (K) and Miquelianin (Q), in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, and a solvent or a mixture of solvents, preferably a mixture of water and glycerol. In particular, the combination of Astragalin (K) and Miquelianin (Q), more particularly the Castanea sativa leaf extract enriched with Astragalin (K) and Miquelianin (Q), is present in the composition at a concentration of between 0.4% and 0.6% by mass, relative to the total mass of the composition.Advantageously, the solvent mixture comprising water and glycerol is present in an effective quantity for physical and microbiological stabilization action, particularly in a mass ratio between 10 / 90 and 40 / 60, preferably 20 / 80.

[0077] The combination according to the invention can be used in the form of a cosmetic or pharmaceutical agent intended to be incorporated into a composition cosmetic or pharmaceutical, and further comprising a suitable cosmetic or pharmaceutical excipient.

[0078] In this case, the combination according to the invention is in another embodiment preferably solubilized in and / or diluted in a solvent, in particular polar, such as water, advantageously further comprising glycerin as in the product described in Example 5.

[0079] The combination according to the invention in another embodiment can be atomized onto an atomization support such as maltodextrin and be in the form of a powder.

[0080] Cosmetic composition

[0081] The present invention further relates to a cosmetic composition comprising the composition according to the invention as defined above, and a cosmetically acceptable excipient. In the cosmetic composition, the composition according to the invention, as defined above, and comprising in particular the combination of Astragalin (K) and Miquelianin (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1, is then used as a cosmetic active agent.

[0082] Advantageously, the cosmetic active agent is a composition according to the invention, as defined above, comprising a combination of Astragalin (K) and Miquelianin (Q), preferably in the form of Castanea sativa leaf extract enriched in Astragalin (K) and Miquelianin (Q), in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1 and a solvent or a mixture of solvents, preferably a mixture of water and glycerol. In particular, the combination of Astragalin (K) and Miquelianin (Q), more specifically the extract of Castanea sativa leaves enriched with Astragalin (K) and Miquelianin (Q), is present in the composition of cosmetic active agent at a content of between 0.4% and 0.6% by mass, relative to the total mass of the composition.Advantageously, the solvent mixture comprising water and glycerol is present in an effective quantity for physical and microbiological stabilization action, particularly in a mass ratio between 10 / 90 and 40 / 60, preferably 20 / 80.

[0083] In one embodiment of the invention, the cosmetic active agent according to the invention is present in the cosmetic composition at a concentration of 1 x 10⁴% to 10%, preferably 1 x 10⁴% to 5%, and even more preferably 1 x 10³% to 3% by mass, relative to the total mass of the cosmetic composition. Advantageously, the cosmetic active agent according to the invention is present in the cosmetic composition at a concentration of 0.1 to 3% by mass, for example between 1 and 3% by mass, in particular 2% by mass, relative to the total mass of the cosmetic composition.

[0084] Advantageously, the cosmetic agent is effective in inhibiting S. aureus virulence factors by at least 20%, preferably S. aureus lipase activity, preferably at least 30%, compared to a placebo control.

[0085] The term “acceptable” means a cosmetic excipient that is not irritating to the skin, does not induce an allergic response, and is chemically stable.

[0086] Advantageously, Astragalin (K) is present in the cosmetic composition at a concentration of 1x10⁶% to 0.1%, preferably 1x10⁵% to 0.1%, by mass relative to the total mass of the composition. Even more advantageously, Miquélianin (Q) is present in the cosmetic composition at a concentration of 1x10⁶% to 2.3x10⁻²%, preferably 1x10⁵% to 2.3x10⁻²%, by mass relative to the total mass of the composition.

[0087] The compositions according to the invention may contain any suitable solvent, excipient, vehicle, as well as other active ingredients.

[0088] The excipient(s) may thus be chosen from among surfactants and / or emulsifiers, preservatives, buffering agents, chelating agents, denaturing agents, opacifying agents, pH adjusters, reducing agents, stabilizing agents, thickening agents, gelling agents, film-forming polymers, fillers, mattifying agents, gloss-enhancing agents, pigments, colorants, perfumes, and mixtures thereof. The CTFA (Cosmetic Ingredient Handbook, 2016 Edition) describes various cosmetic excipients suitable for use in the present invention.

[0089] Advantageously, the excipient(s) are chosen from the group comprising polyglycerols, esters, polymers and cellulose derivatives, lanolin derivatives, phospholipids, lactoferrins, lactoperoxidases, sucrose-based stabilizers, vitamin E and its derivatives, xanthan gums, natural and synthetic waxes, vegetable oils, triglycerides, unsaponifiables, phytosterols, silicones, protein hydrolysates, betaines, aminoxides, plant extracts, sucrose esters, titanium dioxide, glycines, and parabens, and preferably from the group consisting of steareth-2, steareth-21, glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, the methylparaben, ethylparaben, propylparaben, butylparaben, butylene glycol, caprylyl glycol, natural tocopherols, glycerin, dihydroxycetyl sodium phosphate,isopropyl hydroxycetyl ether, glycol stearate, triisononanoine, octyl cocoate, polyacrylamide, isoparaffin, laureth-7, a carbomer, propylene glycol, hexylene glycol, glycerol, bisabolol, dimethicone, sodium hydroxide, PEG-30 dipolyhydroxysterate, caprylic / capric triglycerides, cetearyl octanoate, dibutyl adipate, grapeseed oil, jojoba oil, magnesium sulfate, EDTA, cyclomethicone, xanthan gum, citric acid, sodium lauryl sulfate, waxes and mineral oils, isostearyl isostearate, propylene glycol dipelargonate, propylene glycol isostearate, PEG-8, beeswax, hydrogenated palm kernel oil glycerides, lanolin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, dioxide titanium, lactose, sucrose, low-density polyethylene, isotonic saline solution, and mixtures thereof.

[0090] The cosmetic composition according to the invention can be selected from a solution, aqueous or oily, an aqueous cream or gel or an oily gel, in particular a shower gel, a milk, an emulsion, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone, a mask, a serum, a lotion, a liquid soap, a dermatological bar, an ointment, a mousse, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of makeup powders, a stick or a lozenge.

[0091] The cosmetic composition may further comprise a cosmetically or dermatologically acceptable excipient selected from surfactants, preservatives, buffering agents, swelling agents, chelating agents, biocidal agents, denaturing agents, opacifying agents, pH adjusters, reducing agents, stabilizing agents, emulsifiers, thickeners, gelling agents, film-forming polymers, solvents, fillers, bactericides, odor absorbers, mattifying agents, conditioning agents, texturizing agents, gloss-enhancing agents, pigments, colorants, perfumes, and chemical or mineral sunscreens, trace elements, and essential oils. These combinations are also covered by the present invention.

[0092] The cosmetic or pharmaceutical composition may further include other active ingredients for the treatment of skin and / or mucous membrane conditions affecting sensitive, sensitized, reactive, fragile, and / or weakened skin and / or mucous membranes, and / or having an effect on increasing, protecting, and / or maintaining the beneficial commensal flora of the skin and / or mucous membranes, inducing a complementary or synergistic effect with the extract according to the invention, chosen, for example, from

[0093] - a combination of sodium hyaluronate, pullulan and sodium alginate in particular marketed in a formulation containing serine, trehalose, urea and glycerin under the name PatcH2O™ by the applicant;

[0094] - other cosmetic ingredients intended for the care of sensitive skin such as a plant extract of Cestrum latifolium as described in application WO2009 / 112590 for example marketed under the name Symbiocell ™ by the applicant, a butter extracted from the fruit of the tree Irvingia gabonensis marketed under the name Irwinol™ by the applicant, an extract of root of Eperua falcata marketed under the name Eperuline™, an N-acetyl-L-Tyrosyl-L-Prolyl-L-Phenylalaninamide peptide (INCI: acetyl tetrapeptide 15) sold under the name Skinasensyl™ by the applicant.

[0095] The cosmetic composition may also contain one or more active ingredients on the cutaneous and / or mucosal microbial flora and / or active ingredients on the skin barrier function, including moisturizing and / or soothing active ingredients, among which are an oligosaccharide obtained by enzymatic synthesis marketed by Solabia under the name BioEcolia™ or an alpha-glucooligosaccharide complex marketed by the same company under the name Ecoskin™, an extract of Alisma plantago-aquatica, an extract of Argania spinosa (Lipofructyl™ Argan), a mixture of ceramides (Sphingoceryl™ VEG), purifying extracts of Boldo (Betapur™), products based on inulin or fructooligosaccharides, extracts of bifidobacteria or an extract of Orthosiphon stamineus to combat oily skin (MAT-XS™ Bright), a natural honey extract marketed by the applicant under the name Melhydran™ for its moisturizing properties,a flax extract marketed under the name Oligolin™ by the Applicant, a yeast extract modified by biotechnology and marketed by the Applicant under the name Relipidium™, a Pueraria lobata root extract marketed under the name Inhipase™ by the Applicant, a beta-glucan derivative from baker's yeast marketed by Mibelle under the name CM-Glucan Forte™ and / or a Mirabilis jalapa extract marketed under the name Pacifeel™ by Sederma, N-methylglycine as a cutaneous prebiotic notably marketed under the name Scalposine™ by the Applicant, a barrier function repair agent extracted from phytosterols of Brassica campestris seed oil marketed by the Applicant under the name Phytosoothe™, a moisturizing and soothing agent containing beta-glucans and marketed under the name Hydrasensyl glucan™ by the Applicant,a moisturizing agent comprising hyaluronic acid and konjac polysaccharides marketed under the name Ultra Filling Spheres™, an antioxidant, anti-inflammatory, anti-redness agent containing an extract of Inonotus obliquus marketed by the applicant under the name Inolixir™ soothing, an agent protecting against the effects of pollution, including an extract of Moringa oleifera seeds marketed by the applicant under the name Purisoft™.

[0096] An object of the invention also relates to the non-therapeutic cosmetic use of a cosmetic composition according to the invention, for the cosmetic treatment of healthy skin and / or sensitive healthy mucous membranes, healthy skin and / or sensitized healthy mucous membranes, healthy skin and / or fragile healthy mucous membranes, healthy skin and / or weakened healthy mucous membranes, healthy dry skin and / or mucous membranes, and / or healthy skin with atopic tendencies.

[0097] The present invention also relates to the non-therapeutic cosmetic use of a cosmetic composition according to the invention as a soothing agent and / or moisturizing agent, in particular by its properties to maintain and / or restore the skin and / or mucosal barrier and limit insensible water loss.

[0098] The invention further relates to a cosmetic care method characterized in that it comprises the topical application to at least one area of ​​healthy skin and / or healthy mucous membranes of a cosmetic composition according to the invention, for the cosmetic treatment of sensitive healthy skin and / or healthy mucous membranes, sensitized healthy skin and / or healthy mucous membranes, fragile and / or weakened healthy skin and / or healthy mucous membranes, dry healthy skin and / or healthy mucous membranes, and healthy skin and / or healthy mucous membranes with atopic tendencies, and / or as a soothing agent or a moisturizing agent.

[0099] In an advantageous embodiment of the invention, the cosmetic care process comprises the topical application of the cosmetic composition according to the invention to all or part of the body and / or face, advantageously chosen from the legs, feet, armpits, hands, thighs, belly, décolleté, neck, arms, torso, back, face including the forehead, cheeks, nose, temples, T-zone (forehead, nose and chin) and / or scalp, more advantageously the armpits, scalp and / or face, most advantageously the face and even more advantageously the forehead, cheeks, nose, temples, T-zone (forehead, nose and chin).

[0100] The inventors have demonstrated, in particular, that the combination of Astragalin (K) and Miquelianin (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, exhibits a synergistic effect that provides a significant protective effect on healthy skin and, in particular, soothes sensitive or sensitized healthy skin, fragile or weakened healthy skin, dry healthy skin, and healthy skin prone to atopic dermatitis. The combination according to the invention notably strengthens the skin's barrier function, particularly that of healthy skin. The combination according to the invention promotes healthier and more comfortable skin. It relieves skin discomfort.

[0101] In one embodiment, the amount of the combination of Astragaline (K) and Miquélianine (Q) in the cosmetic composition does not give a therapeutic effect.

[0102] Advantageously, the invention also relates to a cosmetic treatment method for preventing and / or reducing the unsightly and / or uncomfortable manifestations of S. aureus virulence and / or of healthy skin and / or of healthy mucous membranes that are sensitive and / or sensitized and / or fragile and / or weakened and / or dry and / or prone to atopic dermatitis in an individual who needs / wants it, comprising the steps: a. The identification on the individual of an area of ​​healthy skin and / or mucous membrane where one wishes to prevent and / or reduce the unsightly and / or uncomfortable manifestations of S. aureus virulence and / or where one wishes to prevent and / or reduce the sensitivity and / or fragility and / or dryness and / or atopic tendency, and b. The topical application to this area of ​​healthy skin and / or healthy mucous membrane of a cosmetic composition containing the combination according to the invention in an amount effective to prevent and / or reduce the unsightly and / or uncomfortable manifestations of the virulence of S. aureus on this area of ​​skin and / or mucous membrane and / or in an amount effective to prevent and / or reduce its sensitivity and / or fragility and / or dryness and / or atopic tendency, namely in a content of the combination between 1x104% and 10% by weight, preferably between 1x104% and 5% by weight, more advantageously between 1x103% and 3% by weight, more preferably between 0.001% and 0.1% by weight, relative to the total weight of the composition.

[0103] Pharmaceutical or dermatological composition

[0104] The invention further relates to a pharmaceutical and / or dermatological composition comprising a composition according to the invention, as defined above, and a pharmaceutically and / or dermatologically acceptable excipient. In the pharmaceutical and / or dermatological composition, the composition according to the invention, as defined above, and comprising in particular the combination of Astragaline (K) and Miquelianine (Q) in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1, is then used as the active pharmaceutical or dermatological ingredient.

[0105] Advantageously, the pharmaceutical or dermatological active ingredient is a composition according to the invention, as defined above, comprising a combination of Astragalin (K) and Miquelianin (Q), preferably in the form of Castanea sativa leaf extract enriched with Astragalin (K) and Miquelianin (Q), in a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.3, in particular between 1 / 2.5 and 1 / 3.3, especially between 1 / 2.8 and 1 / 3.2 or between 1 / 2.9 and 1 / 3.1, and a solvent or mixture of solvents, preferably a mixture of water and glycerol. In particular, the combination of Astragalin (K) and Miquelianin (Q), more specifically Castanea saliva leaf extract enriched with Astragalin (K) and Miquelianin (Q), is present in the cosmetic active ingredient composition at a concentration of between 0.4% and 0.6% by mass, relative to the total mass of the composition. Advantageously, the solvent mixture comprising water and glycerol is present in an effective quantity for physical and microbiological stabilization, particularly in a mass ratio of between 10 / 90 and 40 / 60, preferably 20 / 80.

[0106] In one embodiment of the invention, the pharmaceutical and / or dermatological composition according to the invention comprises the pharmaceutical and / or dermatological active ingredient according to the invention at a concentration of 1 x 10⁴% to 10%, preferably from 1 x 10⁴% to 5%, and further preferably from 1 x 10³% to 3% by mass, relative to the total mass of the composition. Advantageously, the pharmaceutical and / or dermatological active ingredient according to the invention is present in the pharmaceutical and / or dermatological composition at a concentration of 0.1 to 3% by mass, for example between 1 and 3% by mass, in particular 2% by mass, relative to the total mass of the pharmaceutical and / or dermatological composition.

[0107] Advantageously, Astragaline (K) is present in the pharmaceutical and / or dermatological composition at a concentration of 1 x 10⁶% to 0.1%, preferably 1 x 10⁵% to 0.1%, by mass relative to the total mass of the pharmaceutical and / or dermatological composition. Further advantageously, Miquélianine (Q) is present in the pharmaceutical and / or dermatological composition at a concentration of 1 x 10⁶% to 2.3 x 10⁻²%, preferably 1 x 10⁵% to 2.3 x 10⁻²%, by mass relative to the total mass of the pharmaceutical and / or dermatological composition.

[0108] The pharmaceutical and / or dermatological composition, comprising the combination Astragaline (K) and Miquélianine (Q) is advantageously administered topically or orally, and advantageously applied topically to all or part of the body, advantageously chosen from the legs, feet, armpits, hands, thighs, abdomen, décolleté, neck, arms, torso, back, face including the forehead, cheeks, nose, temples, T-zone (forehead, nose and chin) and / or scalp, more advantageously the armpits, scalp and / or face, most advantageously the face and even more advantageously the forehead, cheeks, nose, temples, T-zone (forehead, nose and chin).

[0109] The pharmaceutically or dermatologically acceptable excipient(s) may be chosen from surfactants and / or emulsifiers, Preservatives, buffering agents, chelating agents, denaturing agents, opacifying agents, pH adjusters, reducing agents, stabilizing agents, thickening agents, gelling agents, film-forming polymers, fillers, mattifying agents, gloss enhancers, pigments, colorants, perfumes, and mixtures thereof. The CTFA (Cosmetic Ingredient Handbook, 2016 Edition) describes various cosmetic excipients suitable for use in the present invention. A person skilled in the art can adapt the formulation of the composition according to the invention using their general knowledge.

[0110] The pharmaceutical and / or dermatological composition according to the invention can be selected from a solution, aqueous or oily, an aqueous cream or gel or an oily gel, in particular a shower gel, a milk, an emulsion, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or siliconed, a mask, a serum, a lotion, a liquid soap, a dermatological bar, an ointment, a foam, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of makeup powders, a stick or a lozenge.

[0111] The invention further relates to a pharmaceutical and / or dermatological composition according to the invention, as defined above, for use as an anti-inflammatory agent, antibacterial agent and / or in the treatment and / or prevention of skin and / or mucous membrane infections associated with S aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, in particular diaper rash, and / or in the prevention and / or pharmaceutical treatment, particularly dermatological treatment, of pathologies related to reactive and / or atopic skin.

[0112] The pharmaceutical and / or dermatological composition is therefore particularly suitable for the treatment of pathologies related to reactive skin and / or mucous membranes, intolerant and / or atopic skin and / or mucous membranes.

[0113] The present invention also relates to the use of a pharmaceutical and / or dermatological composition according to the invention, as defined above, for the manufacture of an anti-inflammatory, antibacterial drug, and / or for the treatment and / or prevention of skin and / or mucous membrane infections associated with S aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, in particular diaper rash, and / or in the prevention and / or pharmaceutical treatment, particularly dermatological treatment, of pathologies related to reactive and / or atopic skin.

[0114] Advantageously, Astragaline (K) is present in the pharmaceutical and / or dermatological composition at a concentration of 1x106% to 0.1%, Preferably, 1 x 10⁵% to 0.1%, by mass relative to the total mass of the pharmaceutical and / or dermatological composition. Even more advantageously, Miquélianin (Q) is present in the pharmaceutical and / or dermatological composition at a concentration of 1 x 10⁶% to 2.3 x 10⁻²%, preferably 1 x 10⁵% to 2.3 x 10⁻²%, by mass relative to the total mass of the pharmaceutical and / or dermatological composition.

[0115] The present invention further relates to a method of treatment and / or prevention and / or reduction of the occurrence of pathologies related to the virulence of S. aureus, in particular to the lipase activity of S. aureus such as inflammation, bacterial infection, and / or skin infections associated with S. aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, in particular diaper rash, and / or in the prevention and / or pharmaceutical treatment, in particular dermatological treatment, of pathologies related to reactive and / or atopic skin in a subject, comprising the topical application of a therapeutically effective amount of the pharmaceutical and / or dermatological composition according to the invention, as defined above, to said subject.

[0116] The invention will now be illustrated by means of the examples below. Other objects, features, and advantages of the invention will become clear to those skilled in the art upon reading the explanatory description, which refers to examples. These examples are given by way of illustration and are in no way intended to limit the invention.

[0117] The examples form an integral part of the present invention and any feature which appears new in relation to any prior art from the description taken as a whole, including the examples, forms an integral part of the invention in its function and in its generality.

[0118] Thus, each example has a general scope.

[0119] Furthermore, in the examples, and unless otherwise indicated, temperature is expressed in degrees Celsius and pressure is atmospheric pressure. EXAMPLES

[0120] Example 1: Preparation of an extract of Castenea saliva according to the invention

[0121] An extract according to the invention is prepared under the following conditions:

[0122] A quantity of 230 g of dried and ground Castenea sativa leaves of French origin (Ardèche and Cher) was extracted in 1865.60 g of reverse osmosis water as the sole solvent for one hour with stirring at a temperature of 80°C. The crude extract was centrifuged and filtered (0.45 µm). The extract is thus obtained in liquid form.

[0123] The extract obtained (dry extract = 3.2%) comprises the following compounds:

[0124] Kampferol-3-O-glucoside (=Astragaline): 0.0058 g / 100 ml

[0125] Quercetin-3-O-glucuronide (= Miquélianin): 0.0174 g / 100 ml

[0126] Other batches were analyzed and showed the compounds in similar concentrations and a K / Q mass ratio between 1 / 1.5 and 1 / 3.5

[0127] The extract according to Example 1 was tested at 0, 1 and 0.3% (w / v) for its ability to inhibit the following virulence factors of S aureus: - on inhibition of S. aureus biofilm formation: the extract showed strong biofilm inhibition properties. - On the inhibition of S. aureus hyaluronidase. - on the inhibition of plasminogen activation into plasmin by S. aureus (protocol in example 4)

[0128] In addition to inhibiting the activity of S. aureus lipase, the extract according to Example 1 of the invention exhibited very good inhibitory properties of these three factors.

[0129] Example 2: Demonstration of the synergistic effect of the combination of Miquélianin (Q) and Astragaline (K) according to the invention on the inhibition of S. aureus lipase activity

[0130] Materials and methods:

[0131] S. aureus (Staphylococcus aureus ATCC 35556) is inoculated with 1 million bacteria in a culture broth (TSB-F Biomérieux index 42614) and incubated at 37°C with the tested molecules or without any additions (negative control) for 24 hours. At the end of the incubation, the growth of S. aureus is determined by measuring the optical density at 600 nm of the bacterial suspension. The supernatant of the culture broth is recovered by centrifugation (1000 g for 5 minutes). The supernatant is then used to evaluate the lipase activity secreted by S. aureus. Lipase activity is determined by adding a chromogenic substrate (Sigma 30058) to a phosphate buffer stabilized at pH 8. After an incubation of one hour at 40 °C, lipase activity is obtained by measuring fluorescence (emission at 600 nm and excitation at 520 nm).The results are expressed as a percentage of inhibition compared to the control (=culture broth without product) and presented as mean + / - standard deviation.

[0132] The molecules were obtained from Extrasynthese (Ref 1243S for astragalin and refl315 for miquelianin) and are added to the culture broth at the doses indicated in weight relative to total volume (broth + molecule tested)

[0133] Results:

[0134] The significance test is the t-test with p<0.01

[0135] [Tables 1] Miquelianin (Q) 0.02% w / v Astragalin (K) 0.01% w / v Miquelianin (Q) 0.02% w / v + Astragalin (K) 0.01% w / v Control Negative Test 1 92 112 60 105 Test 2 85 85 51 103 Test 3 86 79 43 93 Mean 88 92 51 100 Standard deviation 4 17 9 7

[0136] The combination of Miquélianin (Q) 0.02% w / v and Astragalin (K) 0.01% w / v (K / Q mass ratio = 1 / 2) significantly inhibited S. aureus lipase activity by 49%. This inhibition was significantly greater than that induced by Miquélianin (Q) 0.02% alone (P<0.01) or by Astragalin (K) 0.01% alone (P<0.05). The combination had a synergistic effect.

[0137] Example 3: Demonstration of the effect of the K / Q ratio on the inhibition of S. aureus lipase activity

[0138] Materials and methods:

[0139] S. aureus (Staphylococcus aureus ATCC 35556) is inoculated with 1 million bacteria in a culture broth (TSB-F Biomérieux index 42614) and incubated at 37°C in the presence of the products to be tested for 24 hours. At the end of the incubation, the growth of S. aureus is determined by measuring the optical density at 600 nm of the bacterial suspension. The supernatant of the culture broth is recovered by centrifugation (1000 g for 5 minutes). The supernatant is then used to evaluate the lipase activity secreted by S. aureus. Lipase activity was determined by adding a chromogenic substrate (Sigma 30058) to a phosphate buffer stabilized at pH 8. After incubation for one hour at 40 °C, lipase activity was measured by fluorescence (emission at 600 nm and excitation at 520 nm). Results are expressed as a percentage of inhibition relative to the control (culture broth without the substrate) and presented as mean ± standard deviation.

[0140] Results:

[0141] [Tables2] Miquelianin (Q) 0.02% w / v + Astragalin (K) 0.01% w / v Miquélianin (Q) 0.0225% w / v + Astragalin (K) 0.0075% w / v Test 1 51 41 Test 2 51 38 Test 3 51 44 Test 4 55 42 Test 5 76 42 Test 6 57 62 Test 7 51 49 Test 8 45 Mean 56 46 Standard deviation 9 7 (P = 0.009)

[0142] The results show that the mass ratio 1 / 3 (Q 0.0225% + K 0.0075%) is significantly better than the mass ratio 1 / 2 (Q 0.02% + K 0.01%) for the same total amount of Miquelianin and Astragalin (=0.03%). Thus, the mass ratio of 1 / 3 for K / Q exhibits a more pronounced synergistic effect than the mass ratio of 1 / 2 for K / Q.

[0143] Example 4 Effect of the combination according to the invention on the inhibition of the activation of plasminogen into plasmin by S. aureus.

[0144] The combination of Miquélianin (Q) 0.02% w / v and Astragalin (K) 0.01% w / v at a mass ratio K / Q = 1 / 2 was also tested for its ability to inhibit the activation of plasminogen to plasmin by S. aureus and thus act on the barrier function

[0145] Simplified protocol:

[0146] Simplified protocol for the inhibition test of the activation of Plasminogen to Plasmin:

[0147] S. aureus (Staphylococcus aureus ATCC 35556) was inoculated with 10 million bacteria in culture broth (TSB-F bioMérieux index 42614) and incubated at 37°C for 24 hours. At the end of the incubation, the growth of S. aureus was determined by measuring the optical density at 600 nm of the bacterial suspension. The optical density at 600 nm of the bacterial suspension was adjusted to 1.3 and then centrifuged at 1600 g for 10 minutes. The supernatant of the culture broth was collected to evaluate the activation of plasminogen to plasmin as follows.

[0148] For this purpose a defined quantity of plasminogen (40 mil, Sigma P7999) was added with the product to be tested and the chromogenic substrate of plasmin (the Bodipy-Casein Sigma E6638) to the supernatant.

[0149] After incubation for 2 (T2h) and 3 hours (T3h) at 37°C, the hydrolysis of the substrate by plasmin was quantified by fluorescence measurement (emission at 538 nm and excitation at 488 nm). The results are expressed as a percentage relative to the control (=sampling of culture broth without product) and presented as mean ± standard deviation.

[0150] Molecules tested:

[0151] Quercetin-3-O-glucuronide = Miquelianin - Supplier Extrasynthèse 1315 lot 22688-79-5

[0152] Kaempferol-3-O-glucoside = Astragalin - Supplier Extrasynthèse 1243S lot 480-10-4

[0153] Result:

[0154] [Tables3] UFR 485 / 538 nm T2h UFR 485 / 538 nm T3h Mean ET Mean ET Control without bacteria 0 0 0 0 Control with bacteria 100 4 100 3 Astragalin 0.01% + Miquelianin 0.02% 10 1 28 1

[0155] The combination according to the invention strongly inhibited the activation of plasminogen into plasmin by S. aureus.

[0156] Example 5: Example of a composition according to the invention comprising a Castanea saliva extract in the form of a cosmetic agent

[0157] A composition comprising the following compounds is prepared according to methods known to those skilled in the art: (the proportions are expressed as % by weight).

[0158] [Tables4] Composition Content (w / w) relative to total composition Glycerin 80.0% Water 19.5% (19.4-19.6%) Castanea sa tiva leaf extract obtained according to example 1 0.5% (0.4 - 0.6%)

[0159] Example 6: Double-blind test on dry skin

[0160] The objective of the study was to evaluate the effects of the extract according to Example 5 at 2% (w / w), formulated in the emollient balm of Example 7.1. The in vivo study was conducted on 22 adult women and men with dry skin.

[0161] T0 corresponding to measurements taken before treatment

[0162] The so-called placebo cream corresponding to balm 7.1 in which the extract according to example 5 (= the cosmetic agent) has been replaced by water.

[0163] The study was conducted double-blind with the tested cream. The effects on atopic-prone skin were quantified by measuring transepidermal water loss (TEWL) and skin pH as determined by a dermatologist, before, after 14 days, 28 days, and 56 days of treatment with the tested composition. Users also self-assessed the benefit of the products on their skin after 14 and 56 days of treatment.

[0164] Regarding pH: the highest pH values ​​were measured in itchy and very dry areas of atopic-prone skin. Increased skin alkalinity is also associated with greater susceptibility to skin infections (Chikakane and Takahashi, 1995). Maintaining or restoring an acidic pH is therefore of primary importance for preserving or restoring normal barrier function. The cream containing the extract decreased the skin surface pH over time, achieving a significant acidification of 0.26 pH units after 56 days of treatment, unlike the placebo cream, with which no significant pH change was observed.

[0165] On transepidermal water loss (TEWL): Balm 7.1 containing the extract according to Example 5 (= the cosmetic agent) showed a significant decrease in transepidermal water loss (TEWL) at the skin level over time, significantly greater than the decrease observed with the placebo cream. After 14 days of treatment, Balm 7.1 containing the extract according to Example 5 (= the cosmetic agent) reduced transepidermal water loss by 10% (p<0.1) versus T0. After one and two months of treatment with Balm 7.1, significant improvements in barrier function were observed: -21% (p<0.001 vs T0, p<0.1 vs placebo) and -27% (p<0.001 vs T0, p<0.05 vs placebo). Compared with the placebo cream, transepidermal water loss were reduced by 1.7 times (p<0.1) and by 1.5 times (p<0.05) after one and two months of use of balm 7 respectively. Containing the cosmetic agent at 2% (w / w)

[0166] This in vivo demonstration shows the properties of the extract containing the two molecules in the ratio according to the invention to improve the barrier function of skin prone to atopic dermatitis.

[0167] Self-assessment:

[0168] After 14 days of treatment with the balm containing the 2% cosmetic agent, the majority of volunteers perceived improvements in their skin: more hydrated (82%, p<0.001) and softer (73%, p<0.01). Such benefits were not perceived to a significant extent by a majority of users of the placebo cream. After 56 days of treatment, the benefits perceived with the balm 7.1 according to the invention were maintained, and the majority of volunteers reported that their skin felt more soothed (73%, p<0.05).

[0169] Balm 7.1 containing the agent according to the invention improves the epidermal barrier function (TEWL), helps to improve skin pH and reduces lesions, and users have reported having more hydrated, softer and soothed skin.

[0170] Example 7: Cosmetic compositions.

[0171] The cosmetic agent is that of example 5).

[0172] Example 7.1 Body balm for dry, atopic-prone skin

[0173] [Tables5] Phase Name Quantity (% by weight before al) A Water 68.5 A Phenoxyethanol / ethylhexylglycerin 1.00 B Glyceryl stearate / PEG 100 stearate 3.00 B Glyceryl stearate 2.50 B Behenyl alcohol 2.00 B Octyldodecanol 2.00 B Liquid paraffin 5.00 B Ethylhexyl stearate 4.00 B Cocoglycerides 4.00 B Mineral oil 5.00 B Dimethicone 1.00 C Cosmetic agent 2

[0174] The balm is prepared by the usual methods in the field well known to the person skilled in the art, by mixing the 3 phases and adjusting the composition to a pH of 6.15.

[0175] Example 7.2 Emollient Cream for Atopic-Prone Skin

[0176] [Tableauxô] Phase Name Quantity (% by weight before al) A Sodium stearoyl glutamate 0.5 A Cetearyl alcohol 3.00 A Hydrogenated vegetable glycerides 2.00 A Myristyl myristate 1.00 A Caprylyl caprylate / caprate 3.00 A Cocoglycerides 3.00 A Coco-caprylate / caprate 6.00 B Water 71.64 B Xanthan gum 0.30 B Magnesium aluminum silicate 1.50 B Glycerin 5.00 B Trisodium dicarboxymethyl alaninate 0.20 C Cosmetic agent 2.00 D Citric acid 0.86

[0177] The cream is prepared by the usual methods in the field well known to those skilled in the art, by mixing the 4 phases and adjusting the composition to a pH of 4.9.

[0178] Example 7.3 Foam

[0179] [Tables7] Phase Name Quantity (% by weight before al) A Water 42.15 A Sodium Benzoate 0.55 A Lauryl Glucoside, Polyglyceryl 2, Dipolyhydroxystearate, Glycerin 4.00 A Sodium Stearoyl Glutaman 1.00 B Behenyl Alcohol 4.00 B Caprylic / Capric Triglyceride 15.00 B Coco-Caprylate / Caprate 15.00 B Coco-Caprylate 15.00 B Xanthan Gum 0.30 C Cosmetic Agent 2.00 D Citric Acid (50% solution) 1.00

[0180] The cream is prepared by the usual methods in the field well known to those skilled in the art, by mixing the 4 phases and adjusting the composition to a pH of 5.

Claims

Demands

1. Composition comprising a combination of Astragalin (K) and Miquelianin (Q) characterized in that the mass ratio K / Q is between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.

3.

2. Composition according to claim 1, characterized in that the combination of Astragaline (K) and Miquelianine (Q) is contained in a plant extract, preferably an extract of Castanea saliva leaves, enriched in Astragaline (K) and Miquelianine (Q) so as to have a K / Q mass ratio of between 1 / 1.5 and 1 / 3.5, preferably between 1 / 2 and 1 / 3.

3.

3. Composition according to claim 2, characterized in that the extract is obtained by extraction in water, preferably at a temperature between 70 and 90 °C, for example for 30 minutes to 2 hours.

4. Composition according to any one of claims 2 to 3, characterized in that the extract comprises the combination of Astragalin (K) and Miquélianin (Q) in an amount between 0.001 g / 100 ml of extract and 1 g / 100 ml of extract, preferably between 0.01 g / 100 ml of extract and 0.1 g / 100 ml of extract, in particular between 0.02 g / 100 ml of extract and 0.03 g / 100 ml.

5. Composition according to any one of claims 1 to 4, comprising a content of the combination of Astragalin (K) and Miquélianin (Q) of between 0.4 and 0.6% by mass relative to the total mass of the composition.

6. Cosmetic composition comprising a composition as defined in any one of claims 1 to 5 and a cosmetically acceptable excipient.

7. Dermatological composition comprising a composition as defined in any one of claims 1 to 5 and a dermatologically acceptable excipient for use in the prevention and / or reduction of uncomfortable and / or unsightly manifestations of S. aureus virulence on healthy skin and / or mucous membranes and / or for the cosmetic treatment of sensitive healthy skin and / or mucous membranes, sensitized healthy skin and / or mucous membranes, fragile and / or weakened healthy skin and / or mucous membranes, and dry skin and / or mucous membranes. healthy, and healthy skin and / or mucous membranes with atopic tendencies, and / or as a soothing or moisturizing agent.

8. Pharmaceutical and / or dermatological composition comprising a composition as defined in any one of claims 1 to 5 and a pharmaceutically and / or dermatologically acceptable excipient.

9. Pharmaceutical and / or dermatological composition as defined in claim 8, for use as an anti-inflammatory agent, antibacterial agent and / or in the treatment and / or prevention of skin and / or mucous membrane infections associated with S. aureus such as eczema, seborrheic or atopic dermatitis, acne, and cutaneous or mucosal inflammation caused by S. aureus, and / or erythema, in particular diaper rash, and / or in the prevention and / or pharmaceutical treatment, in particular dermatological treatment, of pathologies related to reactive and / or atopic skin.

10. Dermatological composition according to claim 7 or claim 9, wherein the composition is adapted for topical application.