WO2018185408A1

WO2018185408A1 - Protective ingredient for balancing the cutaneous and/or mucosal microbial flora

Info

Publication number: WO2018185408A1
Application number: PCT/FR2018/050801
Authority: WO
Inventors: Isabelle Bonnet; Louis Danoux; Manon GAULT; Sabrina Leoty-Okombi; Boris VOGELGESANG
Original assignee: Basf Beauty Care Solutions France Sas
Priority date: 2017-04-03
Filing date: 2018-03-30
Publication date: 2018-10-11
Also published as: FR3064473A1; FR3064473B1

Abstract

The present invention relates to a new use of pullulan or a derivative thereof in combination with a polysaccharide selected from hyaluronic acid, a salt or derivative thereof, alginic acid, a salt or derivative thereof, and a mixture of said polysaccharides to maintain and/or preserve the balance of the cutaneous and/or mucosal microbial flora.

Description

PROTECTIVE INGREDIENT FOR THE BALANCE OF THE MICROBIAL SKIN FLORA AND / OR MUCOSAL

The present invention relates to the field of cosmetics and the pharmaceutical field, in particular dermatological. The present invention particularly relates to a novel use of pullulan and / or its derivatives in combination with a polysaccharide selected from the group consisting of hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives, especially in the form of a mixture of ingredients to maintain the balance of the bacterial flora of the skin and / or mucous membranes.

The skin is the largest organ of the human body. It has a major role of protection against external aggressions such as environmental aggressions, climatic aggressions, pollution, allergens, pathogenic germs. The skin also represents a complex ecosystem on which several types of microorganisms such as bacteria and fungi proliferate. These microorganisms constitute the cutaneous flora, also called cutaneous microbial flora. We distinguish :

- The beneficial resident flora commensal consisting of microorganisms proliferating conventionally on healthy skin, permanently by drawing their nutrients from the skin, and bringing known benefits to the skin,

- the opportunistic pathogenic resident flora such as Propionibacterium acnes, which normally lives on the skin but which, under certain conditions, can become virulent and therefore potentially pathogenic and

transient flora, present on the skin under abnormal conditions, for example by contact with soiled elements, and which can become pathogenic in the event of proliferation.

Among the microorganisms of the commensal cutaneous flora, there will be mentioned in particular the strain Staphylococcus epidermidis. This strain is found especially on the face on healthy skin where it helps maintain the balance of commensal skin flora. In contrast, the Staphylococcus aurais strain may be considered part of the transient skin flora potentially pathogenic to human skin and Propionibacterium acnes as part of the opportunistic pathogenic resident flora. Staphylococcus aurais and Propionibacterium acnes in case of proliferation can cause a microbial imbalance in the skin flora, which makes it more vulnerable to infections and fungi, induce inflammation, particularly through redness, swelling or even pimples and a burning sensation and / or localized heat accompanied by pain, pigmentation spots or scars for example following acne and therefore an inhomogeneity of the complexion, and finally may be at the origin of real infectious skin diseases such as skin infections such as boils, folliculitis, ulcers, abscesses, sycosis impetigo, ecthyma, erysipelas or acne. In addition, a disturbance of the commensal flora can also be at the origin of mycoses of the skin such as candidiasis. Cosmetic or dermatological solutions are already known to act on the cutaneous microbial flora. On the other hand, their actions are often antiseptic. These modes of action are thus not targeted because they are not directed against a strain of specific microorganism. There are solutions to act on the cutaneous microbial flora by targeting a group such as bacteria in the field of pharmaceutical ingredients. Examples include antibiotics. However, antibiotics have the disadvantage of not always being tolerated especially in oral administration and further induce the development of resistance. In addition, antibiotics in general act not only on the pathogenic microbial flora, but also on the commensal microbial flora, which can result in the appearance of fungal infections. Therefore, there is an important need in the field of cosmetics and dermatology to provide active ingredients on the cutaneous microbial flora, especially by targeted action on a particular microbial strain or by protecting the commensal flora, which are easily available and do not have the disadvantages or side effects described above.

Unexpectedly, the inventors have discovered that pullulan and / or its derivatives in combination (i.e. in admixture) with another polysaccharide selected from the group consisting of hyaluronic acid and alginic acid and their mixtures, possibly in the form of their respective salts or derivatives, had the ability to: maintain or preserve the balance of cutaneous and / or mucosal microbial flora, in particular

limiting or decreasing strains of pathogenic microorganisms at the level of the skin and / or the mucous membranes, preferably strains of pathogenic bacteria, advantageously strains of opportunistic or transient pathogenic bacteria, in particular Staphylococcus aureus and / or Propionibacterium acnes, plus particularly Staphylococcus would have, in particular by at least one of the following mechanisms:

o inhibiting or limiting the amount of pathogenic strains; o inhibiting or limiting the growth of pathogenic strains;

o inhibiting or limiting the adhesion of pathogenic strains;

o inhibiting or limiting the virulence of pathogenic strains, including the production of virulence factors such as biofilm; o by inhibiting or limiting the effects of an increase in pathogenic strains (soothing effect); and or

by protecting the commensal microorganisms in the skin and / or the mucous membranes, preferably the beneficial commensal (or beneficial resident) bacteria, more preferably Staphylococcus epidermidis, for example by keeping their content constant.

The inventors have thus discovered that the use of pullulan or one of its derivatives in combination with a polysaccharide as described above corresponds to technical problem previously stated without the disadvantages of the prior art.

The proliferation of pathogenic microorganism and / or the decrease of the beneficial and / or mucosal commensal cutaneous microbial flora and therefore the imbalance of the cutaneous and / or mucosal microbial flora is generally responsible for unsightly and / or uncomfortable effects which are not diseases but that we wish to avoid in general for aesthetic reasons such as:

- increased production of sebum (hyperseborhhea) and / or an alteration of its quality which gives a shiny skin, causes the appearance of black spots and / or comedogenesis (appearance of pimples), buttons which can subsequently leave tasks or scars;

-perfection of the complexion of the skin (redness and / or irregularities and / or pigmentary stains and / or scars) and thus inhomogeneity of the complexion,

- feeling of warming up and / or

- development of odors especially in maceration areas and / or folds and / or

- the fall of the hairs.

Especially in the scalp, the proliferation of pathogenic microorganism and / or the decrease of beneficial and / or mucosal commensal cutaneous microbial flora and therefore the imbalance of the cutaneous and / or mucosal microbial flora may also be responsible for the fall of hair and / or the appearance of dandruff.

This imbalance can also be responsible in the most serious cases of pathologies of the skin and / or the mucous membranes, in particular during a decrease in the content of commensal beneficial micro-organisms cutaneous and / or mucosal and / or an increase in the content of pathogenic microorganisms, such as bacterial infections of the skin and / or mucous membranes, ulcers, herpes, boils, folliculitis, abscesses, sycosis, impetigo, ecthyma, perysipelas, mycoses such as candidiasis or dermatophytosis such as scabies and ringworm, and acne, delayed healing of wounds and even their superinfection, inflammation of the skin such as erythema, especially the gluteal theme of the infant.

In particular, the area of skin on which treatment with pullulan in combination with a polysaccharide as described above is particularly useful, is the area of skin or mucosa presenting a large amount of cutaneous microbial flora and / or mucosal such as the face, areas of maceration such as infant seat (under the layers), areas of plaice such as armpits, back of elbows, back of knees, buttocks, crotch , the groin, the belly and / or the neck, and / or the turn of the lips and / or the zone of skin or mucosa whose microbial flora has been altered, for example due to a mechanical, chemical or biological action , such as sunburn (solar erythema), the action of the razor, the use of unsuitable or too astringent cleaning products, pollution, the use of antibiotics, allergens etc. .

It can thus be irritated areas, weakened areas, shaved areas, inflamed areas, scars and / or wounds.

Pullulan is a natural polysaccharide (oste polymer) consisting of maltotriose units (a glucose triholoside), also known as α-1,4-a-1,6-glucan. The three units of glucose that make up maltotriose are linked by an α-1,4-type osidic linkage, while the maltotrioses are connected to each other by α-1,61-type osidic bonds. The applications of pullulan are multiple.

It is mainly known as a thickening or film-forming agent and for its ability to capture and retain water as described in patent application FR7434619.

Hyaluronic acid, its salts and derivatives are some of the best-known moisturizing active ingredients currently used. Hyaluronic acid is a polymer of disaccharides, themselves composed of D-glucuronic acid and DN- acetylglucosamine, linked together by alternating glycosidic bonds beta-1,4 and beta-1,3. It is therefore a natural glycosaminoglycan. It is one of the main components of the extracellular matrix. Its different fractions, depending on their molecular weight, can be used as a moisturizing agent as described in patent application US2008 / 0003271.

Alginic acid and its derivatives (base conjugates, salts and esters) are natural polysaccharides obtained from a family of brown algae: laminaria or fucus. Alginate is a polymer formed from two monomers bonded together: mannuronate or mannuronic acid, some of which are acetylated, and guluronate or guluronic acid. The link is via beta 1-4. Alginates are used as thickeners, gelling agents, emulsifiers and stabilizers of various industrial products. They are also known as having water retention properties.

The mixture of a pullulan with another polysaccharide selected from hyaluronic acid and alginic acid and mixtures thereof, optionally in the form of their respective salts or derivatives has already been described by the Applicant in the previous patent application published under number WO2014027163 A2 for its properties to:

reduce insensible water losses

to maintain the water content of the skin and / or the mucous membranes,

to increase the water content of the skin and / or mucous membranes

to increase and / or prolong the content of cosmetic and / or pharmaceutical active ingredients, in particular dermatological ingredients in the skin and / or the mucous membranes, in particular in the cutaneous epidermis.

None of the effects previously described, however, made it possible to predict the protective effect of the mixture on the balance of the cutaneous and / or mucosal microbial flora, in particular when it is used alone (without cosmetic or pharmaceutical active ingredients) or only with a cosmetic or pharmaceutical active ingredient selected from the group consisting of trehalose, serine, urea and mixtures thereof. The present invention therefore relates to the cosmetic use of pullulan or a derivative thereof in combination with a polysaccharide selected from the group consisting of hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides to maintain and / or preserve the balance of cutaneous and / or mucosal microbial flora. Advantageously, the polysaccharide used in combination with the pullulan consists of a mixture of hyaluronic acid or one of its salts or derivatives and alginic acid or one of its salts or derivatives.

For the purposes of the present invention, the term "combination" means that the compounds (pullulan or one of derivatives and polysaccharides) are used together, preferably in the form of a premix. Advantageously, there is no covalent bond between the various compounds of the combination.

For the purposes of the present invention, the term "mucosa (s)", the ocular mucosa, the vaginal mucosa, the urogenital mucosa and / or the oral mucosa, especially the oral labial mucosa and / or the gingival mucosa, preferentially , ocular and / or oral mucosa, and even more preferably, the labial and / or ocular mucosa.

For the purposes of the present invention, the term "maintain and / or preserve the balance of the cutaneous and / or mucosal microbial flora", reduce and / or limit the increase of the pathogenic microbial flora and / or its cutaneous effects. and / or mucosal undesirable, and / or maintain and / or increase and / or protect the commensal beneficial microbial flora and / or increase the ratio of the content of one or more commensal microbial strains to the content of one or more pathogenic microbial strains, particularly transient pathogens or opportunistic pathogens, in the skin and / or mucous membranes.

For the purposes of the present invention, the term "decrease and / or limit the increase of pathogenic microbial flora", inhibit or limit the amount of pathogenic strains and / or inhibit or limit the growth of pathogenic strains (see Example 1 ), and / or inhibit or limit adhesion to the skin or mucosal pathogenic (transient or opportunistic) strains and / or inhibit or limit the virulence of pathogenic strains, including the production of virulence factors such as biofilm production (see Example 5) and / or inhibit or limit the effects of an increase in pathogenic strains.

For the purposes of the present invention, the term "pathogenic microorganism" is intended to mean a microorganism present on the skin and / or the mucous membranes in a non-permanent (transient) manner or a microorganism which normally lives on the skin but which under certain conditions may become virulent. and therefore potentially pathogenic (resident opportunistic pathogen) and inducing or capable of inducing non-pathological alterations of the skin and / or mucous membranes such as skin imperfections such as, for example, redness, dandruff and / or hair loss and / or hair, swelling or even pimples and / or a burning sensation and / or localized heat accompanied by pain, pigmentation spots or scars for example following acne and therefore an inhomogeneity of the complexion, and may be involved in real skin diseases including skin infections, such as boils, folliculitis, abscesses, ulcers, sycosi s, ecthyma, erysipelas, acne or impetigo, see pathological conditions, such as fungal infections (such as candidiasis or dermatophytosis) such as scabies, ringworm and fungal infections caused by Candida albicans, malassezia, Streptococci, Propionibacterium acnes, Staphylococci and especially Staphylococcus ciureus.

For the purposes of the present invention, the term "maintain and / or protect the commensal beneficial microbial flora cutaneous and / or mucosal" to maintain a constant content in the skin and / or mucous membranes of one or more strains of commensal microorganisms chosen in the group consisting of fungi, yeasts and bacteria, preferentially bacteria, present or made on the skin or mucous membranes, especially human and whose action is beneficial for the skin and / or mucous membranes such as Staphylococcus hominis, S warneri, S. capitis, S. epidermidis, preferentially Staphylococcus epidermidis. For the purposes of the present invention, the term "commensal strain" means a strain or flora beneficial to the skin and / or the mucous membranes, which does not or does not become pathogenic for the skin and / or the mucous membranes.

Several methods can be used to measure the content of strains of microorganisms in the skin and / or mucous membranes, including a count of colonies present on the skin or mucous membranes, an in vitro optical density measurement after recovery of samples containing the strains or a PCR measurement. Advantageously, the content of the microorganisms is measured in vitro by optical density after recovery of samples containing the strains.

For the purposes of the present invention, the use of pullulan or a derivative thereof in combination with a polysaccharide according to the invention for increasing the commensal beneficial microbial flora cutaneous and / or mucosal prevents the growth of strains of pathogenic microorganisms at the level of the skin and / or mucous membranes. Here, the term "prevent" prevents the appearance of pathogenic strains in the skin and / or mucous membranes, and not treat. It is therefore a cosmetic use and not a therapeutic treatment.

According to the invention, the use of pullulan or one of its derivatives in combination with a polysaccharide according to the invention is not for improving the barrier function of the skin or for increasing the hydration of the skin and / or mucous membranes neither for the treatment of dry skin.

According to the invention, the term "microbe" encompasses both bacteria and fungi, in particular pathogens. The extract according to the invention therefore has a role of regulating the cutaneous microbial flora, by preventing and / or limiting the development of a pathogenic, opportunistic or transient strain, such as the S. aureus strain and / or the P strain. acnes.

Thus advantageously the cosmetic use according to the invention (and therefore non-therapeutic) is to prevent and / or reduce and / or eliminate the unsightly and / or uncomfortable effects due to the proliferation of pathogenic microorganisms, such as opportunistic or transient pathogenic microorganisms. , and / or the imbalance of the cutaneous and / or mucosal microbial flora, in particular for preventing and / or reducing and / or delaying the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular for preventing and / or or reduce and / or retard the formation of black spots and / or comedogenesis, and / or maintain and / or improve the homogeneity of the complexion of the skin and / or mucous membranes, for example by suppressing and / or reducing redness and / or or irregularities, and / or prevent and / or treat the sensation of heating of the skin and / or mucous membranes and / or prevent and / or reduce and / or eliminate the development of odors and / or to prevent and / or to reduce hair loss and / or hair, and / or to prevent and / or reduce dandruff.

For the purposes of the present invention, the term "maintain and / or improve the homogeneity of the complexion of the skin and / or mucous membranes", to prevent and / or reduce and / or treat the imperfections of the complexion, such as redness or irregularities of the skin, so as to make the complexion of the skin and / or mucous membranes more homogeneous and therefore less dull and brighter, and / or to reduce the reddish appearance of the skin by giving it a healthy appearance and / or or fed and therefore a good-looking effect. The measurement of the homogeneity of the complexion of the skin can for example be measured by chromametry or by image analysis. The latter method of measurement in vivo consists of taking high resolution photographs in cross polarized configuration of the face of volunteers taken at 45 ° before and after application of the tested product. On the basis of these digital photographs, an image analysis makes it possible to extract and to quantify specific parameters (for example: L *, a *, b *, C, h °) related to the color, the brightness, the homogeneity, and the texture of the skin.

In an advantageous embodiment, the pullulan or one of its derivatives in combination with a polysaccharide is applied topically, advantageously on specific parts of the body selected from the legs, feet, armpits, hands, neck, throat, cleavage, belly, arms, thighs, hips, buttocks, waist, crotch, groin, torso, back, labial mucosa, face and / or scalp, especially shaved areas, areas of maceration such as infant seat, areas of plaice such as underarms, back of elbows, back of knees, buttocks, crotch, groin, neck, and / or around the lips.

For the purposes of the present invention, the term "topical route" means the application of the combination and / or the composition according to the invention to the surface of the skin and / or mucous membranes, in particular by direct application or by vaporization.

For the purposes of the present invention, the term "cosmetic and / or pharmaceutical ingredient (s)" means one or more plant extracts and / or one or more natural or synthetic molecules and / or their mixtures intended for a particular purpose. cosmetic and / or pharmaceutical application. Cosmetic ingredients are defined in particular by the International Nomenclature of Cosmetic Ingredients (INCI). The term "cosmetic or pharmaceutical active ingredient" means a cosmetic or pharmaceutical ingredient having a cosmetic and / or pharmaceutical efficacy. Active pharmaceutical ingredients correspond to pharmaceutical active ingredients. Categories and examples of cosmetic and / or pharmaceutical active ingredients are provided hereinafter.

For the purposes of the present invention, the term "suitable cosmetic or pharmaceutical vehicle" means that the composition or the components thereof are suitable for use in contact with the skin and / or the human mucosa without toxicity, incompatibility, instability, allergic response, or their equivalents, undue.

The present invention therefore relates to the use of pullulan or a derivative thereof in combination with a polysaccharide selected from the group consisting of hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides.

Particularly advantageously, it is the use of pullulan or one of its derivatives in combination with a mixture of hyaluronic acid, one of its salts or derivatives and alginic acid, one of its salts or derivatives. This association is in particular described in the application WO2014027163. According to the invention, the "derivatives" are preferably esterified derivatives and organomineral derivatives based on silicon.

For the purposes of the present invention, the term "esterified derivatives of pullulan, hyaluronic acid or alginic acid" means all derivatives obtained by single or multiple esterification of a primary or secondary alcoholic function or an acid function of the pullulan, hyaluronic acid or alginic acid, and having on the esterified part a carbon chain comprising from 1 to 6 carbon atoms, advantageously a linear or branched alkyl chain. Within the meaning of the present invention, the term "organomineral derivatives based on silicon of pullulan, hyaluronic acid or alginic acid" all the derivatives which contain at least one silanol (-SiOH), the siloxane derivatives and / or derivatives obtained by condensation of pullulan, hyaluronic acid or alginic acid with a molecule of the family of silanes.

For the purposes of the present invention, the term "salts of hyaluronic acid, or alginic acid", the ionic compounds that result from the neutralization reaction of the acid form of hyaluronic acid or alginic acid by anion, especially inorganic, in particular chloride, sulfate, phosphate, sodium, potassium and magnesium.

Pullulan is produced from starch by the mushroom Aureobasidium pullulans and can be obtained from different ferments of Aureobasidium pullulans. According to the present invention, the pullulan can be used in its aqueous form, possibly saline. The pullulan derivatives that may be used in the context of the present invention are the cosmetically and / or pharmaceutically acceptable derivatives, preferably dermatologically acceptable, that is to say that they are non-toxic for administration to humans, particularly by application. topical and can be applied safely and without causing allergic or inflammatory reaction especially on the skin. In an advantageous embodiment, the pullulan derivatives are chosen from the organomineral derivatives based on silicon usually used in cosmetics such as for example those selected from trimethylsiloxysilylcarbamoyl pullulan and trimethylsilyl pullulan.

Advantageously in the association, the pullulan is not in the form of derivative. In particular, the pullulan has a weight average molecular weight, advantageously measured by steric exclusion chromatography, of less than 500 kDa, advantageously of approximately 200 kDa. Pullulan is commercially available (Chemaster International, China, Hayashibara, Japan).

The salts and derivatives of hyaluronic acid that may be used in the context of the present invention are the cosmetically and / or pharmaceutically acceptable salts or derivatives, which are preferentially dermatologically acceptable. Advantageously, the hyaluronic acid salts are chosen from hydrolysed calcium hyaluronate, hydrolyzed sodium hyaluronate, potassium hyaluronate, sodium hyaluronate, sodium sulfated hyaluronate and mixtures thereof. Advantageously, it is sodium hyaluronate. In an advantageous embodiment, the hyaluronic acid derivatives are chosen from the derivatives conventionally used in cosmetics such as, for example, those chosen from esterified derivatives, in particular ascorbyl hyaluronate, benzyl hyaluronate, propylene glycol hyaluronate, sodium acetylated hyaluronate, sodium hyaluronate butyroyl or hydroxypropyltrimonium hyaluronate, organomineral silicon derivatives, in particular dimethylsilanol hyaluronate, and mixtures thereof.

Advantageously in the combination with pullulan or one of its derivatives according to the invention, hyaluronic acid is in the form of one of its salts. Advantageously, it is sodium hyaluronate. In particular, hyaluronic acid, its salts or esterified derivatives have a weight average molecular weight, advantageously measured by steric exclusion chromatography, greater than 20 kDa, advantageously between 50 and 800 kDa, advantageously between 250 and 450 kDa. Sodium hyaluronate is commercially available in particular from the companies Technidd Chemi-tech, Wuhan Fortuna Chemical, Dalian Chem Imp. and Exp. Group, Afine Chemicals Limited, Javenech SA, Soliance, Maprecos, Landy Enterprise Limited, Chandigarh Medical Corporation, Kartik Enterprises, DSA Exports.

The salts and derivatives of alginic acid that may be used in the context of the present invention are the cosmetically and / or pharmaceutically acceptable salts or derivatives, which are preferentially dermatologically acceptable. Advantageously, the salts of alginic acid are chosen from ammonium alginate, sodium alginate, calcium alginate, magnesium alginate, sodium alginate sulfate and potassium alginate. Advantageously, it is sodium alginate. In an advantageous embodiment, the derivatives of alginic acid are chosen from the derivatives conventionally used in cosmetics, such as, for example, those chosen from esterified derivatives, in particular glycerol alginate or propylene glycol alginate, and organomineral derivatives. silicon of alginic acid, in particular siloxanetriol alginate or methylsilanol carboxymethyl theophylline alginate, and mixtures thereof. In particular, the derivative is propylene glycol alginate. Advantageously in the combination with pullulan or one of its derivatives, according to the invention, the alginic acid is in the form of one of its salts. Advantageously, it is sodium alginate. Advantageously, the alginic acid, its salts or derivatives, in particular esterified or organomineral silicon have a weight average molecular weight, advantageously measured by size exclusion chromatography, between 10 and 600 kDa, preferably between 30 and 550 kDa, still preferably from 100 to 550kDa. Sodium alginate is commercially available, in particular from the companies Laserson S.A, Univar and Danisco Ingredients. BASF, BAM, Penta Manufacturing Company, Vevy Europe.

Advantageously, the alginic acid will be in the form of sodium alginate, propylene glycol alginate or mixtures thereof. The pullulan or one of its derivatives according to the invention is therefore used in combination with a polysaccharide advantageously as described below. This association will be called the association according to the invention.

In one embodiment of the present invention, when the pullulan is in combination with a polysaccharide according to the invention, the ratio by weight of pullulan, or derivatives and polysaccharide is in the range 1 / 0.002 - 1/200, advantageously in the range 1 / 0.2 - 1/20, even more preferably in the range 1/1 - 1/3.

In a first embodiment, the combination according to the invention contains a mixture of pullulan, optionally in derivative form, and hyaluronic acid, optionally in the form of a salt or derivative, in particular esterified, advantageously in the form of hyaluronate. sodium. Advantageously, for an amount x (in g) of pullulan, or especially esterified derivatives, the amount of hyaluronic acid, salts or derivatives in particular esterified, will be between 0.001x and 100x. In particular, the pullulan weight ratio, or especially esterified derivatives / hyaluronic acid, salts or derivatives especially esterified is in the range 1 / 0.001 -1/100, preferably in the range 1 / 0.1 - 1/10, still more preferably it is 1/1.

In a second embodiment, the combination according to the invention contains a mixture of pullulan, optionally in derivative form, and alginic acid, optionally in the form of a salt or derivative, in particular esterified, advantageously in the form of alginate. sodium. Advantageously, for an amount x (in g) of pullulan, or especially esterified derivatives, the amount of alginic acid, salts or derivatives in particular esterified, will be between 0.001x and 100x. In particular, the ratio by weight of pullulan or derivatives especially esterified / alginic acid, salts or derivatives in particular esterified is in the range 1 / 0.001 - 1/100, advantageously in the range 1 / 0.1 - 1/10, even more advantageously included in the range 1/1 - 1/2.

In a third embodiment, the combination according to the invention contains a mixture of pullulan, optionally in the form of a derivative, of hyaluronic acid, optionally in the form of a salt or derivative, especially esterified, advantageously in the form of sodium hyaluronate, and alginic acid, optionally in the form of a salt or derivative, especially esterified, advantageously in the form of sodium alginate. It therefore comprises three compounds. According to this third embodiment, the combination according to the invention advantageously comprises pullulan, sodium hyaluronate and sodium alginate. Advantageously, the ratio by weight of pullulan, optionally in the form of derivatives / hyaluronic acid, salts or ester derivatives / alginic acid, salts or esterified derivatives is in the range 1 / 0.001 / 0.001 to 1/100/100, still advantageously in the range 1 / 0.1 / 0.1 to 1/10/10, even more preferably in the range 1/1/1 to 1/10/10, and even more preferably in the range 1/1/1 to 1 / 2/5. In a preferred embodiment, this ratio is about 1/1/2, more preferably it is 1/1/2.

According to this advantageous embodiment, said combination according to the invention forms a molecular network pluristratified, corresponding to a molecular grid with formation of hydrogen bonds, when the 3 compounds pullulan, optionally in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, salts or esterified derivatives are associated concomitantly, preferably in the form of a premix, preferably at a ratio lying in the range 1/1/1 to 1/10/10, and still more preferably in the range 1/1/1 to 1/2/5, preferably a ratio of 1/1/2.

In addition, the inventors have realized that this combination according to the invention, in particular when it comprises the three compounds, has a strengthened activity, in a sustainable way, and this in particular because of the formation of a molecular network when the 3 pullulan compounds, optionally in the form of derivatives, hyaluronic acid, salts or ester derivatives, and alginic acid, salts or esterified derivatives are associated concomitantly, preferably in the form of a premix, preferably at a ratio found in the range 1/1/1 to 1/10/10, and even more preferably in the range 1/1/1 to 1/2/5, preferably a ratio of 1/1/2.

The combination according to the invention, and preferably in the form of the 3 compounds (pullulan or its derivative, hyaluronic acid, its salt or derivative and alginic acid, its salt or derivative) is preferably used alone or in the form of a mixture of cosmetic or pharmaceutical ingredients further comprising a cosmetic or pharmaceutical vehicle, in particular a dermatological vehicle, suitable for its formulation and / or its integration into a cosmetic or pharmaceutical composition, especially a dermatological composition. The combination according to the invention may also be used in a cosmetic or pharmaceutical composition, especially a dermatological composition, that is to say in combination with a suitable cosmetic or pharmaceutical vehicle, in particular a dermatological vehicle, and preferably intended for administration by the route. topical. Preferably, said combination according to the invention consists of a mixture of the 3 compounds (pullulan, optionally in the form of derivatives, hyaluronic acid, salts or ester derivatives, and alginic acid, salts or esterified derivatives) preferably at a ratio lying in the range 1/1/1 to 1/10/10, and even more preferably in the range 1/1/1 to 1/2/5, preferably a ratio of 1/1/2.

According to a particular embodiment, the combination according to the invention preferably the combination of the 3 compounds is in the form of a mixture of cosmetic or pharmaceutical ingredients, in particular dermatological, advantageously intended to be incorporated into a cosmetic composition or pharmaceutical, in particular dermatological, further comprising a suitable cosmetic or pharmaceutical vehicle. Advantageously, the vehicle of the mixture of cosmetic or pharmaceutical ingredients is and / or contains water.

Advantageously, the combination according to the invention is then included in the mixture of cosmetic or pharmaceutical ingredients, in particular dermatological ingredients, at a content of 0.001% to 20% by weight of dry matter per relative to the total weight of the mixture of cosmetic or pharmaceutical ingredients, more preferably between 0.01 and 10% by weight, still more advantageously between 0.1 and 5% by weight, in particular between 0.25 and 3% by weight, more particularly between 1 and 3%, even more particularly 1% by weight. According to an advantageous embodiment, the mixture of cosmetic or pharmaceutical ingredients, especially dermatological ingredients, comprises pullulan or a cosmetically or pharmaceutically acceptable derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the product. mixture of ingredients, more advantageously between 0.001% and 5% by weight, even more advantageously between 0.01 and 3% by weight, in particular between 0.1 and 1% by weight, more particularly between 0 and , 25 and 0.5% by weight, very particularly 0.25% by weight and

hyaluronic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 0.001% and 5% by weight; weight, more preferably between 0.01 and 3% by weight, in particular between 0.1 and 1% by weight, more particularly between 0.1 and 1% by weight, even more particularly between 0.25 and 0.5% by weight; by weight, very particularly 0.25% by weight and / or

alginic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 0.001% and 5% by weight; weight, more preferably between 0.01 and 3% by weight, even more advantageously between 0.1 and 2% by weight, still more particularly 0.5% by weight.

According to a preferred embodiment, the mixture of cosmetic or pharmaceutical ingredients comprises the combination of pullulan or one of its derivatives, hyaluronic acid, or one of its salts or derivatives and alginic acid or 'a of its salts or derivatives, preferably at a ratio of between 1/1/1 and 1/10/10, preferably between 1/1/1 and 1/2/5, more preferably at a ratio of 1/1 / 2.

The mixture of cosmetic or pharmaceutical ingredients, especially dermatological, may further comprise a cosmetic or pharmaceutical active ingredient selected from the group consisting of trehalose, serine, urea and mixtures thereof.

According to a particularly advantageous embodiment, the mixture of cosmetic or pharmaceutical ingredients, in particular dermatological ingredients, comprises at least the combination according to the invention, preferably pullulan or a derivative, hyaluronic acid, a salt or a derivative and alginic acid, a salt or a derivative, as well as serine, trehalose, urea and water.

The mixture of cosmetic or pharmaceutical ingredients, in particular dermatological ingredients, may be used in a cosmetic or pharmaceutical composition, in particular a dermatological composition, preferably at a content by weight of dry matter relative to the total weight of the composition of between 0.1 and 10%, advantageously between 0.1 and 5%, in particular between 1 to 3%.

In another embodiment of the present invention, the combination according to the invention or the mixture of cosmetic or pharmaceutical ingredients comprising it according to the invention is in the form of a cosmetic or pharmaceutical composition, in particular a dermatological composition, for topical administration further comprising a suitable cosmetic or pharmaceutical vehicle.

Thus, in this embodiment of the present invention, the combination according to the invention is included in a cosmetic or pharmaceutical composition, in particular a dermatological composition, in particular intended to be administered to a human, preferably by topical application, preferably cutaneous. Advantageously, the combination according to the present invention is then included in the composition at a content of between 0.0001% and 20% by weight of material. total dry weight relative to the total weight of the composition, more preferably between 0.005 and 10% by weight, still more advantageously between 0.01 and 5% by weight, in particular between 0.02 and 1% by weight, more particularly 0, 03% by weight. The cosmetic or pharmaceutical composition, in particular dermatological, preferably also contains a cosmetic and / or pharmaceutical vehicle and / or excipient, especially a dermatological vehicle.

According to one advantageous embodiment, the cosmetic or pharmaceutical composition, especially the dermatological composition according to the invention, comprises pullulan or a cosmetically or pharmaceutically acceptable derivative thereof in an amount of between 0.0001 and 10% by weight of dry matter relative to the total weight of the composition, and advantageously an amount between 0.001% and 5% by weight, more advantageously between 0.001 and 3% by weight, in particular between 0.005 and 0.1% by weight, more preferably between 0.007 and 0, 02% by weight, and

hyaluronic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of dry matter of the composition, advantageously between 0.001% and 5% by weight; % by weight, more preferably between 0.001 and 3% by weight, in particular between 0.005 and 0.1% by weight, more preferably between 0.007 and 0.02% by weight and / or

alginic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the composition, advantageously between 0.001% and 5% by weight, more preferably between 0.001 and 1% by weight, in particular between 0.007 and 0.2% by weight, still more particularly between 0.01 and 0.1% by weight. According to a preferred embodiment, the cosmetic or pharmaceutical composition contains the combination of pullulan or one of its derivatives, hyaluronic acid, or a salt or derivative thereof and alginic acid or a salt or derivative thereof, preferably at a ratio of 1/1/2.

The cosmetic or pharmaceutical composition or the mixture of cosmetic or pharmaceutical ingredients according to the invention may be in any of the galenical forms conventionally used for topical application, such as liquid or solid forms or even in the form of liquid under pressure. . They may especially be formulated in the form of an aqueous or oily solution, an aqueous cream or gel or an oily gel, in particular in a pot or in a tube, in particular a shower gel, a shampoo, a milk, an emulsion, a hydrogel, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone, a serum, a lotion, in particular in a glass or plastic bottle or in a measuring or aerosol flask, an ampoule, a liquid soap, a paste, a dermatological bread, an ointment, a mousse, a mask, a patch, an anhydrous product, preferably a liquid, pasty or solid product, for example in the form of a stick, in particular a stick or a powder, in particular makeup. In particular, the composition is in the form of a serum, a lotion, a cream, a milk, an ointment, a paste, a mousse, an emulsion, a hydrogel, a shower gel, a mask, a stick of a patch, or makeup powders, preferably a cream or a lotion.

The compositions according to the invention may contain any suitable solvent and / or any suitable vehicle and / or any suitable excipient, optionally in combination with other compounds of interest. They may in particular contain a cosmetically or dermatologically acceptable excipient selected from surfactants, preservatives, buffering agents, blowing agents, chelating agents, biocides, denaturants, 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, shine, pigments, dyes, perfumes and sunscreens chemical or mineral, trace elements, essential oils. These combinations are also covered by the present invention. The CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes various cosmetic and pharmaceutical ingredients commonly used in the cosmetic and pharmaceutical industry, which are particularly suitable for topical use.

Preferably, the compositions according to the invention in the form of a mixture of cosmetic or pharmaceutical ingredients or of a cosmetic or pharmaceutical composition contain at least one cosmetic or pharmaceutical active ingredient, in particular dermatological, and preferably from one to three active ingredients cosmetic or pharmaceutical, in particular dermatological selected from the group consisting of urea, trehalose, serine and mixtures thereof, in particular at least two of these compounds selected from serine, urea and trehalose and advantageously three of these compounds. compounds: serine, urea and trehalose.

The present invention thus relates to the cosmetic use of the combination according to the invention, alone or in the form of a mixture of cosmetic ingredients or a cosmetic composition according to the present invention for maintaining and / or preserving the balance. cutaneous and / or mucosal microbial flora.

Advantageously, the cosmetic use according to the invention (and therefore non-therapeutic) is to prevent and / or reduce and / or eliminate the unsightly and / or uncomfortable effects due to the proliferation of pathogenic microorganisms such as opportunistic or transient pathogenic microorganisms, and or the imbalance of the cutaneous and / or mucosal microbial flora, in particular for preventing and / or reducing and / or delaying the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular for preventing and / or to reduce and / or to delay the formation of black spots and / or comedogenesis, and / or to maintain and / or improve the homogeneity of the complexion of the skin and / or the mucous membranes, and / or to prevent and / or treat the sensation of warming up skin and / or mucous membranes, and / or prevent and / or reduce and / or suppress the development of odor and / or to prevent and / or reduce hair loss and / or hair loss and / or to prevent and / or reduce dandruff.

The combination according to the invention has an anti-inflammatory action related to pathogenic microorganisms (it is not a generalizable anti-inflammatory action because the formaldehyde-induced IL8 tests are ineffective)

The combination according to the invention is topically and / or orally acceptable.

For the purposes of the present invention, the term "topically and / or orally acceptable" means an ingredient suitable for application respectively topically and / or orally, non-toxic, non-irritating to the skin and / or mucous membranes and / or the scalp, not inducing an allergic response, which is not chemically unstable.

The combination according to the invention, especially in the form of a cosmetic or pharmaceutical composition, in particular a dermatological composition, is therefore particularly suitable for the care and / or the treatment of skins and / or mucous membranes, in particular shaved areas, maceration such as infant seat, areas of plaice such as armpits, back of elbows, back of knees, buttocks, crotch, groin, and / or neck, and / or turn of the lips, the areas excessively cleaned. The combination according to the invention is also particularly suitable for use on the mucous membranes, alone or in the form of a cosmetic or dermatological composition, in particular for maintaining and / or preserving the balance of the mucosal microbial flora, advantageously for preventing and / or or reduce and / or eliminate the unsightly and / or uncomfortable effects due to the proliferation of pathogenic microorganisms and / or the imbalance of the mucosal microbial flora, in particular to maintain and / or increase and / or improve the homogeneity of the mucous complexion and / or prevent and / or treat the sensation of heating of the mucous membranes, and / or prevent and / or reduce and / or suppress the development of odor and / or to prevent and / or reduce hair loss and / or hair and / or to prevent and / or reduce dandruff. The combination according to the invention, alone or in the form of a cosmetic composition or pharmaceutical or mixture of cosmetic or pharmaceutical ingredients is also particularly suitable for producing ophthalmic care compositions.

The combination according to the invention, alone or in the form of a cosmetic or pharmaceutical composition or a mixture of cosmetic or pharmaceutical ingredients, may be applied to all or part of the human body chosen from the legs, the feet, the armpits and the hands. , the thighs, the belly, the cleavage, the neck, the arms, the torso, the back, the lining of the lips, the hips, the buttocks, the waist, the face and / or the scalp, advantageously the cleavage and / or the face, still advantageously the face.

The present invention furthermore relates to the combination according to the invention, advantageously in the form of a pharmaceutical ingredient mixture or in the form of a pharmaceutical composition, in particular a dermatological composition, according to the present invention for use in the treatment and / or the prevention and / or reduction of the occurrence of pathologies due to an imbalance of the cutaneous and / or mucosal microbial flora, advantageously involving a decrease in the content of commensal beneficial skin and / or mucosal microorganisms and / or an increase in the content of pathogenic microorganisms, preferably in pathogenic bacteria, in particular Staphylococcus aureus and / or Propionibacterium acnes, advantageously pathologies selected from the group consisting of bacterial infections of the skin and / or mucous membranes, ulcers, herpes , acne, especially superinfected, boils, folliculitis, abscess, sycosi s, impetigo, ecthyma perysipelas, fungal infections such as candidiasis or dermatophytosis such as ringworm, scabies, and / or those induced by malassezia and / or in the treatment and / or prevention of superinfection of wounds, and / or in the treatment and / or prevention of perylhema, in particular diaper rash, and / or in the prevention of age spots and / or acne scars.

Finally, the present invention relates to a method of cosmetic care characterized in that it comprises the application on at least one area concerned of the skin and / or mucous membranes of the face or body, of the combination according to the present invention or of a cosmetic composition or a mixture of cosmetic ingredients comprising, as active agent, the combination according to the invention as defined above, for maintaining and / or preserving the balance of cutaneous and / or mucosal microbial flora, and advantageously for preventing and / or reducing and / or delaying the secretion of sebum and its unsightly manifestations and / or uncomfortable and / or uncomfortable, in particular for preventing and / or reducing and / or delaying the formation of black spots and / or comedogenesis, and / or maintaining and / or improving the homogeneity of the complexion of the skin and / or mucous membranes and / or prevent and / or treat the sensation of heating of the skin and / or mucous membranes, and / or prevent and / or reduce and / or suppress the development of odor and / or to prevent and / or reduce the hair loss and / or hair, and / or p to restore and / or reduce dandruff.

It also relates to a method for treating and / or preventing and / or reducing the occurrence of pathologies due to an imbalance of the cutaneous and / or mucosal microbial flora, advantageously involving a decrease in the content of commensal beneficial skin microorganisms and and / or mucosal and / or an increase in the content of pathogenic microorganisms, preferably in pathogenic bacteria, in particular Staphylococcus aureus and / or Propionibacterium acnes, advantageously pathologies selected from the group consisting of bacterial infections of the skin and / or mucous membranes, ulcers, herpes, acne, especially superinfected, boils, folliculitis, abscess, sycosis, impetigo, ecthyma erysipelas, mycoses such as candidiasis or dermatophytosis ; and / or treatment and / or prevention of superinfection of wounds; and / or treatment and / or prevention of erythema, in particular infant diaper rash, and / or prevention of pigment spots and / or acne scars, advantageously by application to at least one of the affected areas of the skin. skin and / or mucous membranes of the face or body of a patient in need thereof, of an effective amount of the combination according to the present invention or of a pharmaceutical composition or a mixture pharmaceutical ingredients comprising as active agent, the combination according to the invention as defined above.

Other objects, features and advantages of the invention will become apparent to those skilled in the art following the reading of the explanatory description which refers to examples which are given by way of illustration only and which can not in in no way limit the scope of the invention.

The examples are an integral part of the present invention and any features appearing novel from any prior art from the description taken as a whole, including the examples, form an integral part of the invention in its function and its generality. Thus, each example has a general scope. On the other hand, in the examples, and unless otherwise indicated, the temperature is expressed in degrees Celsius and the pressure is the atmospheric pressure.

EXAMPLE 1 Inhibition of the Growth of Transient Staphylococcus Aureus Pathogenic Bacteria by the Product According to the Invention

- Realization of the tested product according to the invention: The product P is obtained by simple mixing of the following compounds:

This product is marketed under the name PATCH20 by the Applicant. - Test protocol on bacterial growth:

S. aurais bacteria (strain ATCC 12600) are cultured until stationary phase in TSB culture medium (Tryptic Soy Broth). Then they are seeded in a microplate at a rate of 10 ⁷ bacteria and incubated 24h at 37 ° C. under aerobic agitation with the product P tested and with water as a control at the final content tested (in% w / w in the total medium). ). Sodium dodecyl sulfate (SDS) is used as a negative growth control. Bacterial growth is estimated by measuring the optical density OD at 600 nm.

Table 1: Growth rate of bacteria in the presence of product P

Product P inhibited bacterial growth of S. aureus significantly at the doses tested. Pullulan, sodium alginate and sodium hyaluronate were tested individually at doses corresponding to those of their content in product P at the doses tested. The results show the existence of a synergistic effect of the use of these three ingredients in the product P with respect to each of these ingredients taken individually.

Example 2; Soothing effect of the inflammation induced by transient pathogenic bacteria Staphylococcus aureus by the product according to the invention

The product P tested is that of Example 1 at 0.5%, 0.25% and 0.125% by weight relative to the weight of the total final medium (medium and P). The test is carried out on human keratinocytes HacaT in culture. The HaCaT keratinocytes are incubated at a rate of 2 × 10 ⁶ cells / cm ² . The cells are incubated for 3 to 5 days at 37 ° C. under 5% CO ₂ and 95% relative humidity in a DMEM (Dulbecco Modified Essential Medium) culture medium supplemented with 10% fetal calf serum. The culture medium is then replaced with 1mL of EMEM (Eagle's Minimal Essential Medium) medium. The cells are incubated in the presence of the product to be tested for 24 hours until the cell layer is saturated.

An amount of 0.1 ml of bacterial suspension of S. aurais (ATCC12600) (1.5x10 ⁷ ) is added to each well for 2 hours at 37 ° C., 5% of CO ₂ under aerobic conditions under a saturated atmosphere. Then the media containing the bacteria are removed and replaced by EMEM medium containing the product to be tested and the incubation is continued for 24 more hours. The release of inflammatory cytokines is then assayed by EL1SA.

Table 2.1: Evaluation of the effect of the product P at different dosages on the release of IL6 cytokine induced in keratinocytes by the present S. aureus

Table 2.2: Evaluation of the effect of the product P at different dosages on the release of cytokine 1L8 induced in keratinocytes by the present S. aureus Mean% Standard Deviation Significance vs Release of IL8 Control S. aureus

Untreated control 48 8

Inflammation control 100 4

(S. would have)

P at 0.25% + 5. aureus 22 3 P <0.001

P at 0.5% + S. aureus 16 1 P <0.001

Product P induced a decrease in the release of cytokines IL6 and IL8 caused by S. aureus pathogenic bacteria in cultured keratinocytes. This demonstrates the soothing effect of the product P as well as its anti-inflammatory effect.

Example 3: Protection of the growth of commensal resident microorganisms: the bacterium S. epidermidis in the presence or absence of urban pollutants by the product according to the invention.

The product P tested is that of Example 1 at 0.5% by weight relative to the weight of the total final medium (medium and P).

S. epidermidis bacteria (strain ATCC 14990) are cultured until stationary phase in TSB medium. Then they are seeded in a microplate at a rate of 10 ⁷ bacteria and incubated 24h at 37 ° C under aerobic agitation with the product to be tested and urban pollutants and water as control. Urban pollutants are pollution particles of about 20 microns in diameter and consist in particular of PAH (Polycyclic Aromatic Hydrocarbon: Hydrocarbon Aromatic Pol y cyclic) and organic pesticides (such as PCBs and chlorinated pesticides) (Urban Dust sold by the company NIST, USA). They are added to the content of 2.5 mg / ml in the final medium. Sodium dodecyl sulfate (SDS) is used as a negative growth control. The bacterial growth is estimated by measuring the optical density OD at the wavelength of 600 nm. Table 3: Evaluation of the effect of the product P at different dosages on protection of bacteria S. epidermidis (S. pi) in the presence or absence of pollution particles.

This test demonstrates that the product according to the invention induced a slight bacterial growth of S. epidermidis. Pollutants strongly inhibited the bacterial growth of S. epidermidis. In the presence of the product P, this inhibition is slowed down. The product P therefore has a protective effect of the bacterial growth of S. epidermidis in the presence of pollutants. Pullulan, sodium alginate and sodium hyaluronate were tested individually at doses corresponding to those of their content in product P at the doses tested. The results show the existence of a synergistic effect of the use of these three ingredients in the product P with respect to each of these ingredients taken individually.

Example 4: Absence of protection of the growth of opportunistic pathogenic resident microorganisms: the bacterium Propionibacterium acnes in the presence of urban pollutants by the product according to the invention.

The P. acn microorganisms (strain ATCC 6919) are grown to stationary phase in Schaedler medium. The microorganisms are then seeded in a microplate at a rate of 10 ⁷ bacteria and incubated for 72 hours at 37 ° C. under anaerobic conditions. agitation in the presence of product P and urban pollutants and water as control. Urban pollutants are pollution particles of about 20 microns in diameter and consist of PAH (Polycyciic Aromatic Hydrocarbon: Polycyclic Aromatic Hydrocarbon) and organic pesticides (such as PCBs and chlorinated pesticides) (Urban Dust sold by the company). NIST, USA). Sodium dodecyl sulfate (SDS) is used as a negative growth control. Bacterial growth is estimated by measuring the optical density OD at 600 nm wavelength.

Table 4: Evaluation of the Effect of the Product P at Different Dosages on the Protection of P. acnes Bacteria in the Presence or Not of Pollution Particles

bacterial P. acn s. Pollutants strongly inhibited the bacterial growth of P. acnes. In the presence of the product P, this inhibition is not slowed down. The product P therefore has no protective effect of the bacterial growth of P. acnes in the presence of pollutants.

EXAMPLE 5 Inhibition of Virulence Factors: Formation of the Biofilm of the Pathogenic Resident Microorganisms: the Propionibacterium Acnes and Staphylococcus Aureus Bacteria by the Product According to the Invention

The tested products are:

- Pullulan of the product P at the content of 0.005%

Sodium alginate of the product P at the content of 0.01%

Hyaluronic acid of the product P at the content of 0.005%

Product P at the content of 2% Microorganisms 5 and P. acnes are inoculated in a 96-well plate containing superparamagnetic beads at ¹⁰ bacteria per well. The samples are then incubated at 37 ° C. in the presence of the products to be tested and grown in BHI (Brain Heart Infusion) medium aerobically for S. aureus and anaerobically for P. acnes.

Under the action of a magnet placed under the wells the microbeads move more or less depending on the viscosity of the medium which is increased with the formation of the biofilm that traps the microbeads. When the biofilm is totally inhibited, a brown spot with regular contours is formed in the middle of the well. On the contrary, when there is no inhibition, there is no spot.

After 4h incubation for S. aureus and 48h for. acnes the results are as follows:

Well Well Well S. Well Well P. acnes

Witnesses Aureus + Witnesses + Positive Negative Products Positive Negative Products

(Middle training formation of

BHI) Biofilm of S. biofilm P.

aureus acnes

Polymer 1: No Strong Formation Formation of Inhibition

Pullulait Biofilm Formation, Biofilm Inhibition, Intermediate Biofilm Beads Do Not Have Ball Formation Training

(no biofilm control are not negative biofilm) collected collected

(no spot) (no spot)

Polymer 2: No Formation of Inhibition Formation of Few

Biofilm formation alginate, biofilm intermediates, the inhibition of sodium biofilm beads do not form beads do not formation of Biofilm are not collected biofilm collected

(no spot) (no spot)

Polymer 3: No Formation of No Step Formation

Biofilm formation acid, inhibition of biofilm, inhibition

Hyaluronic biofilm beads do not get balls it's not not

gathered together

(no spot) (no spot)

Product P No Strong Formation Training Inhibition Biofilm Formation, Inhibition of Bioiilm, Intermediate Biofilm Beads Do Not Formation Beads Do Not Form No Biofilm Formation Are Not Collected Biofilm Collected

(no spol) (no spot)

At 6 o'clock, this effect has been quantified and expressed as a percentage:

This test demonstrates that the product P strongly inhibited the formation of the S. aureus biofilm. This test also demonstrated that the product P inhibited the formation of the P. acnes biofilm. Very advantageously, the product P inhibited the formation of P. acnes and 5. aureus biofilms. The quantification of the technical effect at 6h demonstrates the synergistic activity of the combination of the 3 polymers of the product P.

Example 6 Mixture of Cosmetic or Pharmaceutical Ingredients According to the Invention Containing the Combination of Sodium Alginate, Sodium Hyaluronate and Pullulan

A mixture of cosmetic or pharmaceutical ingredients having the following formulation in percent by weight is prepared. Denomination Quantity in%

Sodium alginate 0.5

Pentylene glycol 2

Potassium phosphate 0.02

Trehalosc 10

Serine 3

Sodium hyaluronate 0.25

Caprylyl glycol 0.5

Pullulan 0.25

Glycerin 17.5

Polyacrylal of 0.3 glycerin

Urea 10

Disodium phosphate 0.1

QSP Water

The preparation method is as follows: in water buffered to pH6 with a mixture of disodium phosphate / potassium phosphate salts, sodium hyaluronate and pullulan are added. Once the polymer blend is obtained, urea, trehalose, serine and glycerine are added. After complete solubilization, sodium alginate, pentylene glycol, caprylyl glycol and glycerol polyacrylate gel are added to stabilize the product.

EXAMPLE 7 Composition according to the invention in the form of a lotion for the

Phase Denomination Quantity (% by total weight)

A Water 69.90

A Disodium EDTA 0.05

A xanthan gum 0,20

B Stearclh -2 2.00

B Stcreth-21 2.50

B Cetearyl alcohol 1.00

B Propylheptyl caprylate 15.00

C Blend of cosmetic ingredients according to Example 6 3.00

comprising the combination according to the invention D Water 1.00

D Sodium hydroxide (30% in solution) 0, 10

E Mixture of phenoxyelhanol, chlorphenesin, benzoic acid, 1.25

butylene glycol, sorbic acid (Germazide ™ PI3S)

F Mix of polyacrylate-X, isohexadecanc and 4.00

polysorbate 60 (Scpigel ™ SMS 60)

The lotion is prepared by the usual methods in the field well known to those skilled in the art, by mixing the 6 phases.

Claims

Cosmetic use of pullulan or a derivative thereof in combination with a polysaccharide selected from the group consisting of hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides for maintaining and / or maintaining the balance of cutaneous and / or mucosal microbial flora.

Use according to claim 1 for preventing and / or reducing and / or delaying the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular for preventing and / or reducing and / or delaying the formation of black spots and / or comedogenesis, and / or maintain and / or improve the homogeneity of the complexion of the skin and / or mucous membranes, and / or prevent and / or treat the sensation of heating of the skin and / or mucous membranes, and and / or to prevent and / or reduce and / or suppress the development of odor and / or to prevent and / or reduce hair loss and / or hair loss and / or to prevent and / or reduce dandruff.

Use according to claim 1 for limiting or reducing strains of pathogenic microorganisms, advantageously strains of pathogenic bacteria, in the skin and / or mucous membranes, by at least one of the following mechanisms:

o inhibiting or limiting the amount of pathogenic strains;

o inhibiting or limiting the growth of pathogenic strains;

o inhibiting or limiting the adhesion of pathogenic strains;

o inhibiting or limiting the virulence of pathogenic strains, including the production of virulence factors such as biofilm; o inhibiting or limiting the effects of an increase in pathogenic strains; and / or to protect the commensal microorganisms in the skin and / or mucous membranes, preferably the commensal beneficial bacteria.

Use according to claim 3, characterized in that the pathogenic bacteria, advantageously the opportunistic or transient pathogenic bacteria, are Staphylococcus aureus and / or Propionibacterium acnes, and / or the commensal beneficial bacteria are Staphylococcus epidermidis.

Use according to any one of Claims 1 to 4, characterized in that the pullulan or one of its derivatives in combination with a pol-saccharide is applied topically to specific parts of the body selected from the legs, feet and armpits. , hands, neck, décolleté, belly, arms, thighs, hips, buttocks, waist, crotch, groin, torso, back, labial mucosa, face and / or the scalp, especially shaved areas, areas of maceration such as infant seat, areas of plaice such as armpits, back of elbows, back of knees, buttocks, crotch, lumbar groin, neck, and / or around the lips, areas excessively cleaned.

Use according to any one of Claims 1 to 5, characterized in that the pullulan or one of its derivatives is in combination with a mixture of hyaluronic acid, one of its salts or derivatives and alginic acid, of one of its salts or derivatives.

Use according to any one of claims 1 to 6, characterized in that the pullulan has a weight average molecular weight of less than 500 kDa and / or hyaluronic acid, its esterified salts or derivatives have a higher weight average molecular weight at 20 kDa, advantageously between 50 and 800 kDa

8. Use according to any one of claims 1 to 7, characterized in that the hyaluronic acid is in the form of a salt, preferably sodium hyaluronate and / or alginic acid is in the form of a salt, preferably sodium alginate.

9. Use according to any one of claims 1 to 8, characterized in that the pullulan or a derivative thereof is in combination with a polysaccharide selected from hyaluronic acid, a salt thereof or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides and that the ratio by weight pullulan, or derivatives and polysaccharide is included in the range

1 / 0.002 and 1/200.

10. Use according to any one of claims 6 to 9, characterized in that the ratio by weight pullulan, or derivatives / hyaluronic acid, salts or derivatives / alginic acid, salts or derivatives is in the range 1 / 0.001 / 0.001 and 1/100/100, advantageously it is 1/1/2.

1 1. Use according to any one of claims 1 to 10, characterized in that the pullulan or a derivative thereof in combination with a polysaccharide is in the form of a mixture of cosmetic ingredients for incorporation into a cosmetic composition, and further comprising a suitable cosmetic vehicle.

12. Use according to claim 11, characterized in that the pullulan or a derivative thereof in combination with a polysaccharide is present in the mixture of cosmetic ingredients in a content of between 0.001 and 20% by weight of dry matter relative to total weight of the mixture of ingredients, preferably between 0.1 and 5% by weight.

13. Use according to any one of claims 11 or 12 characterized in that the mixture of cosmetic ingredients comprises pullulan or a cosmetically acceptable derivative thereof in a content of between 0.0001 and 10% by weight of dry matter per relative to the total weight of the mixture of cosmetic ingredients, advantageously between 0.1 and 1% by weight and

hyaluronic acid or a cosmetically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the dry matter of the mixture of cosmetic ingredients advantageously between 0.1 and 1% by weight and / or

alginic acid or a cosmetically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the mixture of cosmetic ingredients.

14. Use according to any one of claims 11 to 13 characterized in that the cosmetic ingredient mixture further comprises a cosmetic active ingredient, selected from the group consisting of trehalose, serine, urea and mixtures thereof.

15. Use according to any one of claims 1 to 14, characterized in that the pullulan or a derivative thereof in combination with a polysaccharide or the mixture of cosmetic ingredients comprising it is in the form of a cosmetic composition for topical administration further comprising a suitable cosmetic vehicle.

16. Use according to claim 15 characterized in that the pullulan or a derivative thereof in combination with a polysaccharide is present in the cosmetic composition in a content of between 0.0001% and 20% by weight of material. dry relative to the total weight of the composition, preferably between 0.01 and 5% by weight.

17. Use according to any one of claims 15 or 16 characterized in that the cosmetic composition comprises pullulan or a cosmetically or pharmaceutically acceptable derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the composition advantageously between 0.005 and 0.1% by weight and

hyaluronic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of dry matter of the composition, advantageously between 0.005 and 0, 1% by weight and / or

alginic acid or a cosmetically or pharmaceutically acceptable salt or derivative thereof in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the composition, advantageously between 0.007 and 0.2% by weight; weight.

18. Use according to any one of claims 15 to 17 characterized in that the composition is in the form of a serum, a lotion, a cream, a milk, an ointment, d a paste, a mousse, an emulsion, a hydrogel, a shower gel, a mask, a stick, a patch, or makeup powders, advantageously a cream or lotion.

19. Pullulan or a derivative thereof in combination with a polysaccharide selected from the group consisting of hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides, for its use in treatment and / or prevention and / or the decrease in the occurrence of pathologies selected from the group consisting of infections, in particular bacterial infections, of the skin and / or mucous membranes, ulcers, herpes, boils, folliculitis, abscesses, sycosis , impetigo, ecthyma erysipelas, acne, mycoses such as candidiasis or dermatophytosis, such as ringworm and / or scabies and / or in the treatment and / or prevention of superinfection of wounds, and / or in the treatment and / or prevention of erythema, in particular infant diaper rash, and / or in the prevention of pigment spots and / or acne scars.

20. Pullulan or a derivative thereof in combination with a polysaccharide for use according to claim 19 characterized in that the pullulan or a derivative thereof in combination with a polysaccharide is as defined in any one of claims 1 to 10 .

21. Pullulan or a derivative thereof in combination with a polysaccharide for use according to any one of claims 19 or 20, characterized in that the pullulan or a derivative thereof in combination with a polysaccharide is in the form of a pharmaceutical ingredient mixture or pharmaceutical composition further comprising a suitable pharmaceutical carrier.

22.. Pullulan or a derivative thereof in combination with a polysaccharide for use according to any one of claims 19 to 21, characterized in that the pharmaceutical ingredient mixture or the pharmaceutical composition further comprises a pharmaceutical active ingredient selected from the group consisting of trehalose, serine, urea and their mixtures.

23. Pullulan or a derivative thereof in combination with a polysaccharide for use according to any one of claims 19 to 22, characterized in that it is intended for topical application, in particular on irritated skin and / or mucous membranes, weakened and / or maceration zones