FR3064473A1 - PROTECTIVE INGREDIENT FOR THE BALANCE OF THE MICROBIAL SKIN FLORA AND / OR MUCOSAL - Google Patents

Abstract

The present invention relates to a new use of pullulan or a derivative thereof or its combination with a polysaccharide chosen from hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and one mixing these polysaccharides to maintain and / or preserve the balance of cutaneous and / or mucosal microbial flora.

Description

® FRENCH REPUBLIC

NATIONAL INSTITUTE OF INDUSTRIAL PROPERTY © Publication number:

(to be used only for reproduction orders)

©) National registration number

064 473

52864

COURBEVOIE © Int Cl ⁸ : A 61 K8 / 73 (2017.01), A 61 K31 / 719, 31/728, 31/734, A 61 O 19/00, A 61 P 17/00

A1 PATENT APPLICATION

©) Date of filing: 03.04.17. ® Applicant (s): BASF BEAUTY CAPE SOLUTIONS ©) Priority: FRANCE SAS Simplified joint stock company - FR. @ Inventor (s): BONNET ISABELLE, DANOUX LOUIS, GAULT MANON, LEOTY-OKOMBI SABRINA (43) Date of public availability of the and VOGELGESANG BORIS. request: 05.10.18 Bulletin 18/40. ©) List of documents cited in the report preliminary research: Refer to end of present booklet (© References to other national documents ® Holder (s): BASF BEAUTY CARE SOLUTIONS related: FRANCE SAS Simplified joint-stock company. ©) Extension request (s): ® Agent (s): CABINET BEAU DE LOMENIE.

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

(g / 2 The present invention relates to a new use of pullulan or one of its derivatives or of its association with a polysaccharide chosen from 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 the cutaneous and / or mucosal microbial flora.

FR 3 064 473 - A1

The present invention relates to the field of cosmetics and the pharmaceutical field, in particular dermatology. The present invention particularly relates to a new use of pullulan and / or its derivatives, in particular in the form of a mixture of ingredients making it possible to maintain the balance of the bacterial flora of the skin and / or mucous membranes.

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

- the commensal beneficial resident flora consisting of microorganisms conventionally proliferating 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 skin flora, mention will be made in particular of the Staphylococcus epidermidis strain. This strain is found in particular in the face on healthy skin where it participates in maintaining the balance of the commensal skin flora.

On the other hand, the Staphylococcus aureus strain can be considered as part of the transient cutaneous flora potentially pathogenic for human skin and Propionibacterium acnes as part of the resident opportunistic pathogenic flora. Staphylococcus aureus and Propionibacterium acnes in the event of proliferation can indeed be at the origin of a microbial imbalance in the cutaneous flora, which makes it more vulnerable to infections and mycoses, induce an inflammation expressed in particular by 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 can be at the origin of real infectious skin pathologies 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 the cause 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 therefore not targeted because they are not directed against a specific strain of microorganism. There are solutions that can act on the microbial flora of the skin by targeting a group like bacteria in the field of pharmaceutical ingredients. An example is antibiotics. However, antibiotics have the disadvantage of not always being tolerated, especially when administered orally, and also induce the development of resistance. In addition, antibiotics in general act not only on pathogenic microbial flora, but also on the commensal microbial flora, which can result in the appearance of yeast infections. Consequently, there is an important need in the field of cosmetics and dermatology to provide active ingredients on the cutaneous microbial flora, in particular by targeted action on a particular microbial strain or by protection of the commensal flora, which are readily available. and do not have the disadvantages or side effects previously described.

Unexpectedly, the inventors have discovered that pullulan and / or its derivatives, preferably in combination (that is to say in admixture) with another polysaccharide chosen 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 capacity to: maintain or preserve the balance of the cutaneous and / or mucosal microbial flora, in particular by limiting or reducing the strains of pathogenic microorganisms at the level of the skin and / or mucous membranes, preferably the strains of pathogenic bacteria, advantageously the strains of opportunistic or transient pathogenic bacteria, in particular of Staphylococcus aureus and / or Propionibacterium acnes, more particularly of Staphylococcus aureus, in particular by at least one of the following mechanisms:

o by inhibiting or limiting the quantity of pathogenic strains; o by inhibiting or limiting the growth of pathogenic strains; o by inhibiting or limiting the adhesion of pathogenic strains; o by 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 commensal microorganisms in the skin and / or mucous membranes, preferably beneficial commensal bacteria (or beneficial resident), 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 particular in combination with a polysaccharide as described above answered the technical problem previously stated without the drawbacks of the prior art.

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

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

-perfection of the complexion of the skin (redness and / or irregularities and / or pigment spots and / or scars) and therefore inhomogeneity of the complexion,

- feeling of heating and / or

- development of odors in particular in the maceration areas and / or the folds and / or

- hair loss.

In the scalp in particular, the proliferation of pathogenic microorganisms and / or the decrease in the beneficial commensal cutaneous and / or mucosal microbial flora and therefore the imbalance in the cutaneous and / or mucosal microbial flora may also be responsible for the fall 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 mucous membranes, in particular during a decrease in the content of beneficial commensal microorganisms 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, erysipelas, yeast infections such as candidiasis or dermatophytosis such as scabies and ringworm, and acne, delay in wound healing and even superinfection, inflammation of the skin such as erythema, in particular diaper rash in infants.

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

It can thus be irritated areas, weakened areas, shaved areas, inflamed areas, scars and / or wounds. Pullulan is a natural polysaccharide (osmosis polymer) made up of maltotriose units (a glucose triholoside), also known as a-1,4-a-1,6-glucan. The three glucose units that make up maltotriose are linked by an a-1,4 type sugar link, while the maltotrioses are connected to each other by a a-1,61 type sugar links. The applications of pullulan are multiple.

It is especially 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 among the best known and most used moisturizing active ingredients today. Hyaluronic acid is a polymer of disaccharides, themselves composed of D-glucuronic acid and D-Nacetylglucosamine, linked together by alternating beta-1,4 and beta-1,3 glycosidic bonds. It is therefore a natural glycosaminoglycan. It is one of the main components of the extracellular matrix. Its different fractions, depending on their molecular weights, can be used as a moisturizing agent as described in patent application US2008 / 0003271.

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

The mixture of a pullulan with another polysaccharide chosen from hyaluronic acid and alginic acid and their mixtures, optionally in the form of their respective salts or derivatives has already been described by the Applicant in the previous patent application published under WO2014027163A2 for its properties to:

reduce insensitive water losses to maintain the water content of the skin and / or 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, in particular dermatological active ingredients in the skin and / or the mucous membranes, in particular in skin epidermis.

None of the previously described effects, 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 ingredient) or only with a cosmetic or pharmaceutical active ingredient chosen from the group consisting of trehalose, serine, urea and their mixtures.

The present invention therefore relates to the cosmetic use of pullulan or one of its derivatives, preferably in combination with a polysaccharide chosen 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 the cutaneous and / or mucosal microbial flora. Advantageously, the polysaccharide used in combination with 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 "association" 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 association.

For the purposes of the present invention, the term "mucous membrane (s)" means the ocular mucosa, the vaginal mucosa, the urogenital mucosa and / or the oral mucosa, in particular the labial buccal mucosa and / or the gingival mucosa, preferably , the ocular and / or buccal mucosa, and more preferably, the labial and / or ocular mucosa.

For the purposes of the present invention, the term "maintaining and / or preserving the balance of the cutaneous and / or mucosal microbial flora" means reducing and / or limiting the increase in the pathogenic microbial flora and / or its cutaneous effects and / or unwanted mucosals, and / or maintain and / or increase and / or protect the beneficial commensal 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, in particular transient pathogens or opportunistic pathogens, in the skin and / or mucous membranes.

For the purposes of the present invention, the term "decreasing and / or limiting the increase in pathogenic microbial flora" means inhibiting or limiting the amount of pathogenic strains and / or inhibiting or limiting the growth of pathogenic strains (cf. example 1 ), and / or inhibit or limit the adhesion to the skin or mucous membranes of pathogenic strains (transient or opportunistic) and / or inhibit or limit the virulence of pathogenic strains, including the production of virulence factors such as the production of biofilm (cf. example 5) and / or inhibit or limit the effects of an increase in pathogenic strains.

In the sense of the present invention, the term “pathogenic microorganism” is understood to mean a microorganism present on the skin and / or the mucous membranes in a non-permanent (transient) manner or a microorganism which lives normally on the skin but which under certain conditions can become virulent. and therefore potentially pathogenic (resident opportunistic pathogen) and inducing or capable of inducing non-pathological changes in the skin and / or mucous membranes such as skin imperfections such as redness, dandruff and / or hair loss and / or hair loss, 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 which may be involved in real skin pathologies especially skin infections, such as boils, folliculitis, abscesses, ulcers, sycosi s, ecthyma, erysipelas, acne or impetigo, see pathological conditions, such as yeast infections (such as candidiasis or dermatophytosis) for example scabies, ringworm and yeast infections due to Candida albicans, malassezia, Streptococci, Propionibacterium acnes, Staphylococci and in particular Staphylococcus aureus.

For the purposes of the present invention, the term "maintaining and / or protecting the beneficial commensal microbial flora cutaneous and / or mucosal" means keeping the content in the skin and / or mucous membranes of one or more strains of commensal microorganisms chosen constant. in the group consisting of fungi, yeasts and bacteria, preferably bacteria, present or made on the skin or mucous membranes, in particular human and whose action is beneficial for the skin and / or mucous membranes such as Staphylococcus hominis, S warneri, S. capitis, S. epidermidis, preferably Staphylococcus epidermidis.

For the purposes of the present invention, the term “commensal strain or flora” therefore means a strain or flora beneficial for the skin and / or the mucous membranes, which is not or does not become pathogenic for the skin and / or the mucous membranes.

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

Within the meaning of the present invention, the use of pullulan or of a derivative thereof preferably in combination with a polysaccharide according to the invention for increasing the beneficial commensal microbial flora of the skin and / or mucosa makes it possible to prevent the growth of strains of microorganisms pathogens in the skin and / or mucous membranes. The term "prevent" is understood here to prevent the appearance of pathogenic strains in the skin and / or mucous membranes, and not to treat. It is therefore a cosmetic use and not a therapeutic treatment.

According to the invention, the use of pullulan or of a derivative thereof preferably in combination with a polysaccharide according to the invention is not to improve the barrier function of the skin nor to increase the hydration of the skin and / or mucous membranes or for the treatment of dry skin.

According to the invention, the term "microbe" includes both bacteria and fungi, in particular pathogens. The extract according to the invention therefore has a role in 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 imbalance of the cutaneous and / or mucosal microbial flora, in particular to prevent and / or reduce and / or delay the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular to prevent and / or reduce and / or delay the formation of blackheads and / or comedogenesis, and / or maintain and / or improve the uniformity of the complexion of the skin and / or mucous membranes, for example by removing and / or reducing redness and / 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 suppress the development oppement of odors and / or to prevent and / or reduce hair loss and / or hair, and / or to prevent and / or reduce dandruff.

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

In an advantageous embodiment, the pullulan or one of its derivatives or its association with a polysaccharide is applied topically, advantageously to specific parts of the body chosen from the legs, feet, armpits, hands, neck, cleavage, stomach, arms, thighs, hips, buttocks, waist, crotch, groin, torso, back, labial mucosa, face and / or scalp, in particular shaved areas, maceration areas such as the infant seat, plaice areas such as the armpits, back of the elbows, back of the 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 of 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 mixtures thereof intended for a cosmetic and / or pharmaceutical application. Cosmetic ingredients are notably defined by the international nomenclature of cosmetic ingredients (INCI).

The term “cosmetic or pharmaceutical active ingredient” means a cosmetic or pharmaceutical ingredient having cosmetic and / or pharmaceutical efficacy. The active pharmaceutical ingredients correspond to the active pharmaceutical ingredients. Categories and examples of cosmetic and / or pharmaceutical active ingredients are provided below.

Within the meaning 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 human skin and / or mucous membranes without toxicity, incompatibility, instability, allergic response, or their equivalents, undue.

The present invention therefore relates to the use of pullulan or one of its derivatives preferably in combination with a polysaccharide chosen 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 application WO2014027163.

According to the invention, the "derivatives" are preferably the esterified derivatives and the 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 the derivatives obtained by simple or multiple esterification of a primary or secondary alcoholic function or of 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 pullulan silicon, hyaluronic acid or alginic acid” means all the derivatives which contain at least one silanol (-SiOH) and obtained by condensation of the pullulan, hyaluronic acid or alginic acid with a molecule from the silane family.

For the purposes of the present invention, the term “hyaluronic acid or alginic acid salts” means the ionic compounds which result from the neutralization reaction of the acid form of hyaluronic acid or of alginic acid by an anion, in particular inorganic, in particular chloride, sulphate, phosphate, sodium, potassium and magnesium.

Pullulan is produced from starch by the fungus Aureobasidium pullulans and can be obtained from different ferments of Aureobasidium pullulans. According to the present invention, pullulan can be used in its aqueous form, optionally saline. The pullulan derivatives which can 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, in particular by application. topical and can be applied safely and without causing an allergic or inflammatory reaction, especially on the skin. In an advantageous embodiment, the pullulan derivatives are chosen from organomineral derivatives based on silicon usually used in cosmetics such as for example those chosen from trimethylsiloxysilylcarbamoyl pullulan and trimethylsilyl pullulan. Advantageously in the association, pullulan is not in the form of a derivative. In particular, 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 which can be used in the context of the present invention are the cosmetically and / or pharmaceutically acceptable salts or derivatives, preferably dermatologically acceptable. Advantageously, the hyaluronic acid salts are chosen from hydrolyzed calcium hyaluronate, hydrolyzed sodium hyaluronate, potassium hyaluronate, sodium hyaluronate, sodium sulfated hyaluronate and their mixtures. Advantageously, it is sodium hyaluronate. In an advantageous embodiment, the derivatives of hyaluronic acid are chosen from the derivatives usually used in cosmetics such as for example those chosen from esterified derivatives, in particular ascorbyl hyaluronate, benzyl hyaluronate, l propylene glycol hyaluronate, acetylated sodium hyaluronate, sodium butyroyl hyaluronate or hydroxypropyltrimonium hyaluronate, organomineral silicon derivatives, in particular dimethylsilanol hyaluronate and mixtures thereof.

Advantageously in 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 450kDa. Sodium hyaluronate is commercially available in particular from the companies Technidd Chemi-tech, Wuhan Fortuna Chemical, Dalian Chem lmp. 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 which can be used in the context of the present invention are the cosmetically and / or pharmaceutically acceptable salts or derivatives, preferably 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 alginic acid derivatives are chosen from the derivatives usually used in cosmetics such as, for example, those chosen from esterified derivatives, in particular glycerile alginate or propylene glycol alginate, organomineral derivatives alginic acid silicon, in particular siloxanetriol alginate or methyl alginate carboxymethyl theophylline alginate, and mixtures thereof. In particular, the derivative is propylene glycol alginate. Advantageously in the association with pullulan or one of its derivatives, according to the invention, 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 steric exclusion chromatography, between 10 and 600 kDa, preferably between 30 and 550 kDa, still preferably from 100 to 550kDa. Sodium alginate is available commercially in particular from the companies Laserson S.A, Univar, Danisco Ingrédients. BASF, BAM, Penta Manufacturing Company, Vevy Europe.

Advantageously, the alginic acid will be in the form of sodium alginate, propylene glycol alginate or their mixtures.

Pullulan or one of its derivatives according to the invention can therefore be used in combination with a polysaccharide advantageously as described below. This association will then be called, the association according to the invention.

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

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

In a second embodiment, the combination according to the invention contains a mixture of pullulan, optionally in the form of a derivative, and of alginic acid, optionally in the form of a salt or in particular esterified derivative, advantageously in the form of alginate sodium. Advantageously, for an amount x (in g) of pullulan, or derivatives in particular esterified, the amount of alginic acid, salts or derivatives in particular esterified, will be between 0.001x and lOOx. In particular, the ratio by weight of pullulan or in particular esterified derivatives / alginic acid, salts or in particular esterified derivatives is included 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 in particular esterified derivative, advantageously in the form of hyaluronate of sodium, and alginic acid, optionally in the form of a salt or in particular esterified derivative, advantageously in the form of sodium alginate. It therefore comprises three compounds. According to this third embodiment, advantageously, the combination according to the invention therefore comprises pullulan, sodium hyaluronate and sodium alginate. Advantageously, the weight ratio of pullulan, optionally in the form of derivatives / hyaluronic acid, salts or esterified derivatives / alginic acid, salts or esterified derivatives is included 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 advantageously in the range 1/1/1 to 1/10/10, and even more preferably in the range 1/1/1 to 1 / 2/5. According to a preferred mode, this ratio is around 1/1/2, even more preferably it is 1/1/2.

According to this advantageous embodiment, said association according to the invention forms a multi-layered molecular network, corresponding to a molecular mesh with the formation of hydrogen bonds, when the 3 pullulan compounds, optionally in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, esterified salts or derivatives are associated concomitantly, preferably in the form of a premix, preferably with a ratio in the range 1/1/1 to 1/10/10, and even more preferably in the range 1/1/1 to 1/2/5, advantageously a ratio of 1/1/2.

In addition, the inventors have realized that this association according to the invention, in particular when it comprises the three compounds, had an enhanced activity, in a lasting manner, and this in particular due to the formation of a molecular network when the 3 pullulan compounds, optionally in the form of derivatives, hyaluronic acid, esterified salts or derivatives, and alginic acid, esterified salts or derivatives are associated concomitantly, preferably in the form of a premix, preferably with a ratio found in the range

1/1/1 to 1/10/10, and more preferably in the range 1/1/1 to 1/2/5, advantageously 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, in particular dermatological, vehicle suitable for its formulation and / or for its integration into a cosmetic or pharmaceutical composition, in particular dermatological. The combination according to the invention can also be used in a cosmetic or pharmaceutical composition, in particular dermatological, that is to say in combination with an appropriate cosmetic or pharmaceutical vehicle, in particular suitable dermatological, and preferably intended for administration by route. topical. Preferably, said association according to the invention consists of a mixture of the 3 compounds (pullulan, optionally in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, salts or esterified derivatives) preferably at a ratio found in the range 1/1/1 to 1/10/10, and more preferably in the range 1/1/1 to 1/2/5, advantageously a ratio of 1/1/2.

According to a particular embodiment, the pullulan or one of its derivatives according to the invention or the association according to the invention preferably the association 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 or pharmaceutical composition, in particular dermatological, further comprising a suitable cosmetic or pharmaceutical vehicle. Advantageously, the vehicle for the mixture of cosmetic or pharmaceutical ingredients is and / or contains water.

Advantageously, pullulan or one of its derivatives or 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 relative to the total weight of the mixture of cosmetic or pharmaceutical ingredients, more advantageously between 0.01 and 10% by weight, even 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 mode, the mixture of cosmetic or pharmaceutical, in particular dermatological, ingredients comprises pullulan or one of its cosmetically or pharmaceutically acceptable derivatives in a content of between 0.0001 and 10% by weight of dry matter relative to the total weight of the 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, even more particularly between 0 , 25 and 0.5% by weight, very particularly 0.25% by weight and optionally (in the case of the combination according to the invention) hyaluronic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content 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, more advantageously between 0.01 and 3% by weight, in particular r 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, very particularly 0.25% by weight and / or l 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 , more advantageously between 0.01 and 3% by weight, even more advantageously between 0.1 and 2% by weight, even 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 d '' one 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, even more preferably at a ratio of 1/1 / 2.

The mixture of cosmetic or pharmaceutical, in particular dermatological, ingredients may also comprise an active cosmetic or pharmaceutical ingredient chosen from the group consisting of trehalose, serine, urea and their mixtures.

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

The mixture of cosmetic or pharmaceutical, in particular dermatological, ingredients can be used in a cosmetic or pharmaceutical, in particular dermatological, composition preferably with 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 pullulan or one of its derivatives or the combination according to the invention or the mixture of cosmetic or pharmaceutical ingredients the or comprising it according to the invention is in the form of a cosmetic or pharmaceutical composition, in particular a dermatological composition, intended for topical administration, further comprising a suitable cosmetic or pharmaceutical vehicle.

Thus in this embodiment of the present invention, the pullulan or one of its derivatives or the combination according to the invention is included in a cosmetic or pharmaceutical composition, in particular dermatological, in particular intended to be administered to a human being, preferably by topical application, preferably to the skin. Advantageously, pullulan or one of its derivatives or 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 total dry matter relative to the total weight of the composition, more advantageously between 0.005 and 10% by weight, even 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, in particular dermatological, composition preferably also contains a cosmetic and / or pharmaceutical, in particular dermatological, vehicle and / or excipient.

According to an advantageous embodiment, the cosmetic or pharmaceutical, in particular dermatological, composition according to the invention comprises pullulan or one of its cosmetically or pharmaceutically acceptable derivatives in an amount 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 optionally (in the case of the combination according to the invention)

- 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, 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 / 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 advantageously between 0.001 and 1% by weight, in particular between 0.007 and 0.2% by weight, even 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 one of its salts or derivatives and alginic acid or one of its salts or derivatives, 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 can be in all dosage forms conventionally used for topical application, such as liquid or solid forms or even in the form of a pressurized liquid. . They can in particular be formulated in the form of an aqueous or oily solution, an aqueous cream or gel or an oily gel, in particular in a jar 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-based, a serum, a lotion, in particular in a glass or plastic bottle, in a dosing bottle or in aerosol, an ampoule, a liquid soap, a paste, a dermatological bar, an ointment, a foam, a mask, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of a stick, in particular in stick or in powders, in particular of makeup. In particular, the composition is in the form of a serum, a lotion, a cream, a milk, an ointment, a paste, a foam, an emulsion, d '' a hydrogel, a shower gel, a mask, a stick of a patch, or make-up powders, advantageously 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 chosen from surfactants, preservatives, buffering agents, swelling agents, chelating agents, biocidal agents, denaturants, opacifying agents, pH adjusters, reducing agents , stabilizers, emulsifiers, thickeners, gelling agents, film-forming polymers, solvents, fillers, bactericides, odor absorbers, matting agents, conditioning agents, texturing agents, glossing agents , pigments, dyes, perfumes and chemical or mineral sunscreens, 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 in particular suitable for topical use.

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

The present invention thus relates to the cosmetic use of pullulan or one of its derivatives or of the combination according to the invention, alone or in the form of a mixture of cosmetic ingredients or of a cosmetic composition according to the present invention for maintaining and / or preserving the balance of the 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 imbalance of the cutaneous and / or mucosal microbial flora, in particular to prevent and / or reduce and / or delay the secretion of sebum and its unsightly and / or unpleasant and / or uncomfortable manifestations, in particular to prevent and / or reduce and / or delay the formation of blackheads and / or comedogenesis, and / or maintain and / or improve the uniformity 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 preventing and / or reducing and / or suppressing the development of odor and / or for preventing and / or reducing hair loss and / or po they and / or to prevent and / or reduce dandruff.

Pullulan or one of its derivatives or the combination according to the invention has an anti-inflammatory action linked to pathogenic microorganisms (it is not a generalizable anti-inflammatory action because the IL8 tests induced by formaldehyde are ineffective)

Pullulan, or one of its derivatives or 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 by the topical and / or oral route, non-toxic, non-irritating to the skin and / or the mucous membranes and / or the scalp, not inducing an allergic response, which is not chemically unstable.

Pullulan or a derivative thereof or the combination according to the invention, in particular in the form of a cosmetic or pharmaceutical composition, in particular a dermatological composition, is therefore very suitable for the care and / or treatment of skin and / or mucous membranes. particularly shaved areas, maceration areas such as the infant seat, plaice areas such as the armpits, the back of the elbows, the back of the knees, the buttocks, the crotch, the groin, and / or the neck, and / or around the lips, excessively cleansed areas. Pullulan or one of its derivatives or the combination according to the invention is also very 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 flora. mucosal microbial, advantageously for preventing and / or reducing and / or eliminating the unsightly and / or uncomfortable effects due to the proliferation of pathogenic microorganisms and / or to the imbalance of the mucosal microbial flora, in particular for maintaining and / or increasing and / or improve the uniformity of the complexion of the mucous membranes 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 loss and / or to prevent and / or reduce dandruff. Pullulan or a derivative thereof or a combination according to the invention, alone or in the form of a cosmetic or pharmaceutical composition or a mixture of cosmetic or pharmaceutical ingredients is also very particularly suitable for producing ophthalmic care compositions.

Pullulan or one of its derivatives or 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 can be applied to all or part of the human body chosen from the legs, feet, armpits, hands, thighs, belly, décolleté, neck, arms, torso, back, labial mucosa, hips, buttocks, waist, face and / or leather hair, advantageously the neckline and / or the face, advantageously the face.

The present invention further relates to pullulan or one of its derivatives or the combination according to the invention, advantageously in the form of a mixture of pharmaceutical ingredient or in the form of a pharmaceutical composition, in particular dermatological, according to the present invention for use in the treatment and / or 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 beneficial commensal cutaneous microorganisms 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 from pathologies chosen from the group consisting of bacterial infections of the skin and / or mucous membranes, ulcers, herpes, acne, especially superinfected, s boils, folliculitis, abscesses, sycosis, impetigo, ecthyma erysipelas, yeast 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 erythema, in particular diaper rash in infants, and / or in the prevention of blemishes pigment and / or acne scars.

Finally, the present invention relates to a cosmetic care method characterized in that it comprises the application to at least one affected area of the skin and / or mucous membranes of the face or body, of pullulan or of a derivative thereof or of the combination according to the present invention or of a cosmetic composition or of a mixture of cosmetic ingredients comprising, as active agent, pullulan or one of its derivatives or the combination according to the invention as defined above, to maintain and / or preserve the balance of the cutaneous and / or mucosal microbial flora, and advantageously to prevent and / or reduce and / or delay the secretion of sebum and its unsightly and / or unpleasant manifestations and / or uncomfortable, in particular to prevent and / or reduce and / or delay the formation of blackheads and / or comedogenesis, and / or maintain and / or improve the uniformity of the complexion of the skin and / or mucous membranes its, 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 hair loss and / or hair loss, and / or to prevent and / or reduce dandruff.

It also relates to a method of treatment and / or of prevention and / or of reduction of the occurrence of pathologies due to an imbalance of the cutaneous and / or mucosal microbial flora, advantageously implying a decrease in the content of beneficial cutaneous commensal microorganisms 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 from pathologies chosen from the group consisting of bacterial infections of the skin and / or mucous membranes, ulcers, herpes, acne, in particular superinfected, boils, folliculitis, abscesses, sycosis, impetigo, erythyma erysipelas, fungal infections 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 diaper rash of the infant, and / or prevention of pigment spots and / or acne scars, advantageously by application to at least one affected area of the skin and / or mucous membranes of the face or body of a patient in need thereof, an effective amount of pullulan or of a derivative thereof or of the combination according to the present invention or of a pharmaceutical composition or 'A mixture of pharmaceutical ingredients comprising as active agent, pullulan or one of its derivatives or the combination according to the invention as defined above.

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

The examples form an integral part of the present invention and any characteristic which appears new compared to any prior state of the 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.

Thus, each example is general in scope.

On the other hand, in the examples, and unless otherwise indicated, the temperature is expressed in degrees Celsius and the pressure is atmospheric pressure.

Example 1 Inhibition of the growth of transient pathogenic bacteria Staphylococcus aureus by the product according to the invention

- Realization of the product tested according to the invention:

Product P is obtained by simple mixing of the following compounds:

Last name Amount% by weight / total weight of the mixture water QSP Sodium alginate 0.5 Sodium hyaluronate 0.25 Pullulan 0.25 Pentylene glycol 2 Potassium phosphate 0.02 Trehalose 10 Serine 3 Caprylyl glycol 0.5 Glycerin 17.5 Glycerin polyacrylate 0.3 Urea 10 Disodium phosphate 0.1

This product is marketed under the name PATCH2O by the Applicant.

Bacterial growth test protocol:

5. aureus bacteria (strain ATCC 12600) are cultivated until stationary phase in TSB culture medium (Tryptic Soy Broth). Then they are seeded in a microplate at the rate of 10 ⁷ bacteria and incubated 24h at 37 ° C. aerobically with shaking in the presence of the product P tested and of 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 600nm.

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

Average DO difference type % of growth Significance (p) vs H ₂ O control TSB + S. aureus + H2O 0.99 0.06 100 TSB + S. aureus + SDS 0.00 0.02 0 TSB + 5. aureus + P to 0.91 0.06 92.35 P <0.05

0.25% (w / w) TSB + S. aureus + P to 0.125% (w / w) 0.91 0.06 91.45 P <0.05

Product P inhibited the bacterial growth of S. aureus significantly at the doses tested.

Example 2: Soothing Effect of 1 Inflammation Induced by Transient Pathogenic Staphylococcus Aureus Bacteria 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 HacaT keratinocytes in culture.

HaCaT keratinocytes are incubated at the 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 culture medium (Dulbecco Modified Essential Medium) supplemented with 10% fetal calf serum. The culture medium is then replaced by 1 ml of normal EMEM medium (Eagle's Minimal Essential Medium). The cells are incubated in the presence of the product to be tested for 24 hours until the cell mat is saturated.

An amount of 0.1 ml of bacterial suspension of S. aureus (ATCC12600) (1.5 × 10) is added to each well for 2 h at 37 ° C., 5% of CO 2 aerobically under a saturated atmosphere. The media containing the bacteria are then removed and replaced with EMEM medium containing the product to be tested and the incubation is continued for an additional 24 hours. The release of inflammatory cytokines is then assayed by ELISA.

Table 2.1: Evaluation of the Effect of Product P at Different Assays on the Release of Cytokine IL6 Induced in Keratinocytes by the Present of 5, Aureus

Average of Release of IL6 difference type Significance vs S. aureus control Untreated control 70 9 Ignition control (5. aureus) 100 8 P at 0.125% + S. aureus 66 3 P <0.001 P at 0.25% + 5. aureus 50 6 P <0.001 P at 0.5% + 5. aureus 48 13 P <0.001

Table 2.2: Evaluation of the effect of the product P at different dosages on the release of cytokine IL8 induced in keratinocytes by the present of 5.

aureus

Average of IL8 release Standard deviation Significance vs S. aureus control Untreated control 48 8 Ignition control (S. aureus) 100 4 0.25% P + S. aureus 22 3 P <0.001 P at 0.5% + 5. aureus 16 1 P <0.001

Product P induced a reduction in the release of cytokines IL6 and 1L8 caused by the pathogenic bacteria S. aureus in keratinocytes in culture. This demonstrates the soothing effect of product P as well as its anti-inflammatory effect.

Example 3: Protection of the growth of commensal resident microorganisms: the S. epidermidis bacteria 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).

5. epidermidis bacteria (strain ATCC 14990) are grown until stationary in TSB medium. Then they are seeded in a microplate at the rate of 10 ⁷ bacteria and incubated 24h at 37 ° C aerobically with shaking in the presence of the product to be tested and urban pollutants and water as control. Urban pollutants are pollution particles of about 20 microns in diameter and made up in particular of PAH (Polycyclic Aromatic Hydrocarbon: Polycyclic Aromatic Hydrocarbon) and organic pesticides (such as

PCB 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. Bacterial growth is estimated by measuring the optical density DO at the wavelength of 600nm.

Table 3: Evaluation of the effect of product P at different dosages on protection of the S. epidermidis (S. epi) bacteria in the presence or not of pollution particles.

Average DO Standard deviation % of growth Significance (p) vs condition polluting h ₂ o 1.17 0.07 100 SDS 0.00 0.8 0 P at 0.5% 1.36 0.05 116.26 Pollutants 0.3 0.002 30.37 Pollutants + P to 0.5% 0.452 0.05 45.63 P <0.01

This test demonstrates that the product according to the invention induced a slight bacterial growth of 5. epidermidis. The pollutants strongly inhibited the bacterial growth of 5. epidermidis. In the presence of product P, this inhibition is slowed down. Product P therefore has a protective effect on the bacterial growth of 5. epidermidis in the presence of pollutants.

Example 4: Lack of protection of the growth of opportunistic pathogenic resident microorganisms; the bacteria Propionibacterium acnes in the presence 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).

The microorganisms P. acnes (strain ATCC 6919) are cultivated until stationary phase in Schaedler medium. Then the microorganisms are seeded in a microplate at the rate of 10 ⁷ bacteria and incubated 72 hours at 37 ° C anaerobically with agitation in the presence of product P and urban pollutants and water as a control. Urban pollutants are pollution particles of around 20 microns in diameter and made up in particular of PAH (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 DO at the wavelength 600nm.

Table 4: Evaluation of the effect of the product P at various dosages on the protection of the bacteria P. acnes in the presence or not of pollution particles

Average DO Standard deviation 0.025% SDS -0.516 0.22 H ₂ O 0.929 0.03 P at 0.5% 0.961 0.04 Pollutants 0.185 0.09 Pollutants + at P 0.5% 0.074 0.10

This test demonstrates that the product according to the invention did not induce bacterial growth of P. acnes. The pollutants strongly inhibited the bacterial growth of P. acnes. In the presence of product P, this inhibition is not slowed down. Product P therefore has no protective effect on the bacterial growth of P. acnes in the presence of pollutants.

Example 5: Inhibition of virulence factors; formation of the biofilm of resident pathogenic microorganisms: the bacterium Propionibacterium acnes and Staphylococcus aureus by the product according to the invention.

The products tested are:

Pullulan of product P with a content of 0.005%

- The sodium alginate of product P 0.01% with the content of

- The hyaluronic acid of product P in the content of 0.005%

- Product P with a content of 2%

The microorganisms S aureus and P. acnes are seeded in a 96-well plate containing superparamagnetic beads at the rate of 10 ⁶ bacteria per well. The samples are then incubated at 37 ° C. in the presence of the products to be tested and cultured in a BHI (Brain Heart Infusion) medium aerobically for 5. aureus and anaerobic 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 which traps the microbeads. When the biofilm is completely 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 4 hours of incubation for S. aureus and 48 hours for P. acnes the results are as follows:

Well Witness negative (Middle BHI) Well Witnesses positive of formation of Biofilm by S. aureus Well 5. aureus + products Well Witnesses positive of formation of biofilm of P. acnes Well P. acnes + products Polymer 1: Pullulan No formation of biofilm (witness negative) Formation of biofilm, the marbles did not not gathered (no spot) Strong inhibition of Training from biofilm Formation of biofilm, the marbles don't are not gathered (no spot) Inhibition intermediate training Biofilm Polymer 2: Alginate sodium No formation of biofilm Formation of biofilm, the marbles don't are not gathered (no spot) Inhibition inlermédiair e of formation of Biofilm Formation of biofilm, the marbles don't are not gathered (no spot) Little inhibition of the formation of biofilm Polymer 3: Acid Hyaluronic No formation of biofilm Formation of biofilm, the marbles don't are not gathered (no spot) No inhibition Formation of biofilm, the marbles don't are not gathered (no spot) Not inhibition Product P No formation of biofilm Formation of biofilm, the marbles don't are not gathered (no spot) Strong inhibition of Training Biofilm Formation of biofilm, the marbles don't are not gathered (no spot) Inhibition intermediate training Biofilm

This test demonstrates that the pullulan and the product P strongly inhibited the formation of the biofilm of S. aureus. This inhibition was also observed in the presence of sodium alginate.

This test also demonstrated that the pullulan and the product P inhibited the formation of the biofilm of P. acnes.

Very advantageously, the pullulan and the product P inhibited the formation of the biofilms of P. acnes and of 5. aureus.

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

A mixture of cosmetic or pharmaceutical ingredients having the formulation 10 below in percentage by weight is prepared.

Denomination Quantity in% Sodium alginate 0.5 Pentylene glycol 2 Potassium phosphate 0.02 Trehalose 10 Serine 3 Sodium hyaluronate 0.25 Caprylyl glycol 0.5 Pullulan 0.25 Glycerin 17.5 Glycerin polyacrylate 0.3 Urea 10 Disodium phosphate 0.1 Water QSP

The preparation process 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 mixture of polymers is obtained, urea, trehalose, serine and glycerine are added. After complete solubilization, sodium alginate, pentylene glycol, caprylyl glycol and gel based on glycerol polyacrylate are added so as to stabilize the product.

Example 7: Composition according to the invention in the form of a Lotion for the body and / or the face:

Phase Denomination Quantity (% by weight total) AT Water 69.90 AT Disodium EDTA 0.05 AT Xanthan gum 0.20 B Steareth -2 2.00 B Stereth-21 2.50 B Cetearyl alcohol 1.00 B Propylheptyl caprylate 15.00 VS Mixture of cosmetic ingredients according to Example 6 including the association according to the invention 3.00 D Water 1.00 D Sodium hydroxide (30% solution) 0.10 E Phenoxyethanol mixture, chlorphenesin, benzoic acid, butylene glycol, sorbic acid (Germazide ™ PBS) 1.25 F Polyacrylate-X mixture, isohexadecane and polysorbate 60 (Sepigel ™ SMS 60) 4.00

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

FR 1752864

Claims (22)

1. Cosmetic use of pullulan or one of its derivatives, preferably in combination with a polysaccharide chosen 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 the cutaneous and / or mucosal microbial flora to prevent and / or reduce and / or delay 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 blackheads and / or comedogenesis, and / or maintaining and / or improving the uniformity of the complexion of the skin and / or mucous membranes, and / or preventing 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 hair loss and / or hairs and / o u to prevent and / or reduce dandruff. 2. Use according to claim 1 for limiting or reducing the strains of pathogenic microorganisms, advantageously the strains of pathogenic bacteria, in the skin and / or mucous membranes, by at least one of the following mechanisms: o by inhibiting or limiting the quantity of pathogenic strains; o by inhibiting or limiting the growth of pathogenic strains; o by inhibiting or limiting the adhesion of pathogenic strains; o by 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; July 13, 2017 FR 1752864 and / or to protect commensal microorganisms in the skin and / or mucous membranes, preferably beneficial commensal bacteria. 3. Use according to claim 2, characterized in that the pathogenic bacteria, advantageously the opportunistic or transient pathogenic bacteria, are Staphylococcus aureus and / or Propionibacterium acnes, and / or the beneficial commensal bacteria are Staphylococcus epidermidis. 4. Use according to any one of claims 1 to 3, characterized in that the pullulan or one of its derivatives or its association with a polysaccharide is applied topically to specific parts of the body chosen from the legs, feet, armpits, hands, neck, décolleté, stomach, arms, thighs, hips, buttocks, waist, crotch, groin, torso, back, labial mucosa, face and / or the scalp, in particular the shaved areas, the maceration areas such as the infant seat, the plaice areas such as the armpits, the back of the elbows, the back of the knees, the buttocks, the crotch , groin, neck, and / or around the lips, excessively cleaned areas. 5. Use according to any one of claims 1 to 4, characterized in that the pullulan or one of its derivatives is in association with a mixture of hyaluronic acid, of one of its salts or derivatives and of alginic acid, one of its salts or derivatives. 6. Use according to any one of claims 1 to 5, characterized in that the pullulan has a weight-average molecular weight of less than 500 kDa and / or hyaluronic acid, its salts or esterified derivatives have a mean molecular weight of weight greater than 20 kDa, advantageously between 50 and 800 kDa July 13, 2017 FR 1752864 7. Use according to any one of claims 1 to 6, characterized in that the hyaluronic acid is in the form of a salt, advantageously sodium hyaluronate and / or alginic acid is in the form of 'a salt, advantageously sodium alginate. 8. Use according to any one of claims 1 to 7, characterized in that the pullulan or one of its derivatives is in association with a polysaccharide chosen from hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives and a mixture of these polysaccharides and that the pullulan weight ratio, or derivatives and polysaccharide is included in the range 1 / 0.002 and 1/200. 9. Use according to any one of claims 6 to 8, characterized in that the pullulan weight ratio, 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. 10. Use according to any one of claims 1 to 9, characterized in that the pullulan or one of its derivatives or its association with a polysaccharide is in the form of a mixture of cosmetic ingredients intended to be incorporated into a cosmetic composition, and further comprising a suitable cosmetic vehicle. 11. Use according to claim 10, characterized in that the pullulan or one of its derivatives or its association 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 the total weight of the mixture of ingredients, advantageously between 0.1 and 5% by weight. July 13, 2017 FR 1752864 12. Use according to any one of claims 10 or 11 characterized in that the mixture of cosmetic ingredients comprises pullulan or one of its cosmetically acceptable derivatives in a content of between 0.0001 and 10% by weight of dry matter per relative to the total weight of the mixture 5 of cosmetic ingredients, advantageously between 0.1 and 1% by weight and possibly - 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 dry matter in the mixture 10 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 ingredients 15 cosmetics. 13. Use according to any one of claims 10 to 12 characterized in that the mixture of cosmetic ingredient further comprises an active cosmetic ingredient, chosen from the group consisting of trehalose, serine, 20 urea and mixtures thereof. 14. Use according to any one of claims 1 to 13, characterized in that the pullulan or one of its derivatives or its association with a 25 polysaccharide or the mixture of cosmetic ingredients comprising it is in the form of a cosmetic composition intended for topical administration further comprising a suitable cosmetic vehicle. July 13, 2017 FR 1752864 15. Use according to claim 14. characterized in that the pullulan or one of its derivatives or its association with a polysaccharide is present in the cosmetic composition in a content of between 0.0001% and 20% by weight of dry matter relative to total weight of the composition, advantageously between 0.01 and 5% by weight. 16. Use according to any one of claims 14 or 15 characterized in that the cosmetic composition comprises pullulan or one of its cosmetically or pharmaceutically acceptable derivatives 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 optionally 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. 17. Use according to any one of claims 14 to 16 characterized in that the composition is in the form of a serum, a lotion, a cream, a milk, an ointment, '' a paste, a foam, an emulsion, a hydrogel, a shower gel, a mask, a stick, a patch, or make-up powders, advantageously a cream or lotion. July 13, 2017 FR 1752864 18. Pullulan or one of its derivatives, preferably in combination with a polysaccharide chosen 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 the treatment and / or prevention and / or reduction of the occurrence of pathologies due to an imbalance of the cutaneous and / or mucosal microbial flora, advantageously implying a decrease in the content of beneficial cutaneous commensal microorganisms 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 from pathologies chosen from the group consisting of infections, in particular bacterial infections, of the skin and / or mucous membranes, ulcers, herpes, boils, folliculitis, abscesses, syco sis, impetigo, ecthyma erysipelas, acne, yeast infections such as candidiasis or dermatophytosis, such as ringworm and / or scabies and / or in the treatment and / or prevention of secondary infection wounds, and / or in the treatment and / or prevention of erythema, in particular diaper rash, and / or in the prevention of pigmentation spots and / or acne scars. 19. Pullulan or one of its derivatives or its association with a polysaccharide for its use according to claim 18 characterized in that the pullulan or one of its derivatives or its association is as defined in any one of claims 1 to 9. 20. Pullulan or one of its derivatives or its association with a polysaccharide for its use according to any one of claims 18 or 19, characterized in that the pullulan or one of its derivatives or its association is in the form of a mixture of A pharmaceutical ingredient or a pharmaceutical composition further comprising a suitable pharmaceutical carrier. July 13, 2017 FR 1752864 21. Pullulan or one of its derivatives or its association with a polysaccharide for its use according to any one of claims 18 to 20, characterized in that the mixture of pharmaceutical ingredients or the composition 5 pharmaceutical further comprises an active pharmaceutical ingredient selected from the group consisting of trehalose, serine, urea and mixtures thereof. 22. Pullulan or one of its derivatives or its association with a polysaccharide for its use according to any one of claims 18 to 21, characterized 10 in that it is intended for topical application, in particular on irritated, weakened skin and / or mucous membranes and / or maceration areas July 13, 2017 FRENCH REPUBLIC