FR3132023A1 - PROTECTIVE INGREDIENT FOR THE SKIN AND/OR MUCOUS MOUSSES AGAINST VIRULENCE FACTORS - Google Patents

Abstract

PROTECTIVE INGREDIENT FOR THE SKIN AND/OR MUCOUS MOUSSES AGAINST VIRULENCE FACTORS The present invention relates to a new combination comprising pullulan or one of its derivatives, a polysaccharide chosen from hyaluronic acid, one of its salts or derivatives, alginic acid, one of its salts or derivatives or a mixture thereof, succinic acid, one of its salts or derivatives, lactic acid, one of its salts or derivatives and sucrose, one of its salts or derivative, particularly useful to prevent and/or reduce the virulence of C. acnes.

Description

PROTECTIVE INGREDIENT FOR THE SKIN AND/OR MUCOSA AGAINST VIRULENCE FACTORS

The present invention relates to the field of cosmetics and the pharmaceutical field, in particular dermatology. The present invention particularly relates to a new combination of pullulan and/or its derivatives in association with
- on the one hand 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 and
- on the other hand lactic acid, one of its salts or derivatives, succinic acid, one of its salts or derivatives and sucrose, one of its salts or derivatives.

This new combination is composed of a mixture of compounds having a synergistic action making it possible to limit and/or reduce the virulence of Cutibacterium acnes , in particular the formation of biofilm and thus prevent and/or reduce uncomfortable and/or unpleasant manifestations and/ or unsightly virulence factors of Cutibacterium acnes . It also makes it possible to treat pathologies associated/due to the virulence of C. acnes, in particular to the virulence factors of Cutibacterium acnes , such as acne.

The skin is the largest organ of the human body. It has a major protective role against external attacks such as environmental attacks, climatic attacks, pollution, allergens and pathogenic germs. The skin also represents a complex ecosystem in which several types of microorganisms such as bacteria and fungi proliferate. These microorganisms constitute the skin flora, also called skin microbial flora. We distinguish between resident or commensal flora such as Propionibacterium acnes , otherwise called Cutibacterium acnes , which normally lives on the skin. Under certain conditions, certain strains of C. acnes can become more virulent and therefore cause pathologies.

Cutibacterium acnes when it expresses virulence factors can in fact be the cause of unsightly and/or unpleasant and/or uncomfortable manifestations such as redness, swelling or even pimples and a sensation of burning and/or localized heat accompanied pain, pigment spots or scars for example following acne and therefore an inhomogeneity of the complexion. It can also contribute to real skin pathologies such as acne. The alteration caused at the skin barrier by C. acnes can also contribute to real opportunistic infections by other bacteria and/or mycoses such as candidiasis. Cosmetic or dermatological solutions are already known to act on bacteria, for example antiseptics. However, their modes of action are not targeted because they are not directed against a specific strain of microorganism. Antibiotics are then a solution allowing action on a targeted group of skin microbial flora but they have the disadvantages of not always being tolerated, of inducing the development of resistance and of acting on commensal microbial flora, which can also result in the appearance of mycoses. Consequently, there is a significant need in the field of cosmetics and dermatology to provide alternative active ingredients having a targeted action on a particular microbial strain, which are easily available and do not have the disadvantages or side effects previously described.

Unexpectedly, the inventors discovered that a combination comprising:
- pullulan and/or one of its derivatives
- 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
- lactic acid, one of its salts or derivatives
- succinic acid, one of its salts or derivatives and
- sucrose, one of its salts or derivatives
had the capacity to limit and/or reduce the virulence of strains of Cutibacterium acnes , in particular by at least one of the following mechanisms:
- by inhibiting or limiting the adhesion of Cutibacterium acnes strains;
- by inhibiting or limiting the production of virulence factors of Cutibacterium acnes strains, such as biofilm.

The mixture of a pullulan with another polysaccharide chosen from hyaluronic acid and alginic acid and their mixtures, possibly in the form of their respective salts or derivatives has already been described by the Applicant in a previous patent application published under the number WO2014027163A2 for its properties of:
- reduction of imperceptible water losses,
- maintaining the water content of the skin and/or mucous membranes,
- increased water content of the skin and/or mucous membranes, and
- increase and/or prolongation of the content of cosmetic and/or pharmaceutical active ingredients in the skin and/or mucous membranes.

This same mixture has also already been described by the Applicant in a previous patent application published under number FR3064473A1 for its properties of maintaining the balance of the bacterial flora of the skin and/or mucous membranes.

Sucrose has also been described as promoting the specific fermentation of S. epidermidis , which will produce succinic acid, a compound which belongs to the family of short-chain fatty acids (SCFAs) and described in the literature as inhibiting the growth of C. acnes .

Particularly surprisingly, the inventors discovered that the new combination according to the invention exhibited synergistic effects against the virulence factors of C. acnes . The effect of the combination according to the invention on the formation of the C acnes biofilm is in fact greater than the effect obtained on the one hand with the mixture described in the previous patent application published under the number FR3064473A1 and on the other hand share higher than that obtained with a mixture of sucrose, lactic and succinic acid. This synergistic action of the compounds of the new combination according to the invention is demonstrated in Example 2.
Technical problem

The inventors thus discovered that the combination according to the invention responded to the technical problem previously stated without the disadvantages of the prior art in a particularly unexpected manner.

The present invention therefore relates to a combination comprising:
- pullulan or one of its derivatives, and
- 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 mixtures thereof, and
- lactic acid, one of its salts or derivatives, and
- succinic acid, one of its salts or derivatives and
- sucrose, one of its salts or derivatives.

The combination may be in the form of a mixture of the compounds listed above and consist only of these compounds, or may be in the form of a mixture of cosmetic or pharmaceutical ingredients, in particular dermatological for example. example when the combination is associated with xanthan gum and/or glycerin and/or pentylene glycol and/or caprylyl glycol and/or water, advantageously xanthan gum and/or glycerin . The combination can alternatively be in the form of a cosmetic or pharmaceutical composition, in particular dermatological.

The present invention also relates to the cosmetic use of this combination or of the mixture of cosmetic ingredients or of a cosmetic composition comprising the combination according to the invention to limit and/or reduce the virulence of Cutibacterium acnes strains on the skin and/or or the mucous membranes, in particular by at least one of the following mechanisms:
- by inhibiting or limiting the adhesion of Cutibacterium acnes ;
- by inhibiting or limiting the production of Cutibacterium acnes virulence factors such as biofilm.

The present invention also relates to the cosmetic use of the combination according to the invention to prevent and/or reduce unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes .

The present invention also relates to the combination according to the invention, or the mixture of pharmaceutical ingredients according to the invention or the pharmaceutical composition, in particular dermatological, according to the invention for its use as a pharmaceutical active ingredient, in particular dermatological, in particular to prevent and/or treat pathologies due to the virulence of C. acnes, advantageously involving an increase in the secretion of biofilm by C. acnes and/or an increase in the adhesion of C. acnes .

In general, the virulence factors of C. acnes can be responsible for unsightly and/or unpleasant and/or uncomfortable manifestations which are not diseases but which we wish to avoid for aesthetic and/or comfort reasons such as :
- increased production of sebum and/or an alteration of its quality which gives shiny skin, a loss of radiance of the skin, a so-called “dull” or less luminous complexion, causes the appearance of blackheads, an increase the size of the pores of the skin and/or comedogenesis (appearance of pimples), pimples which can subsequently leave spots and/or scars and/or
- an imperfection in the skin tone (redness and/or irregularities and/or pigment spots and/or scars) and therefore inhomogeneity of the complexion and/or
- a feeling of heating and/or
- loss of hair and/or hair and/or
- the appearance of dandruff.

The virulence factors of C. acnes may also contribute, in the most serious cases and under multifactorial favorable conditions, to the appearance of pathologies of the skin and/or mucous membranes, such as bacterial infections of the skin and /or mucous membranes, pustules, papules, boils, folliculitis, abscesses, and/or acne, particularly superinfected, and/or delay in the healing of wounds and even their superinfection and/or a inflammation of the skin and/or mucous membranes. They can also contribute to the appearance of scar marks on the skin in the form of pigment spots and/or acne scars.

In particular the area of skin on which the treatment using the combination according to the invention, optionally in the form of a mixture of cosmetic or pharmaceutical ingredients or of a cosmetic or pharmaceutical composition, is particularly useful, is the area of skin or mucosa presenting a large quantity of cutaneous and/or mucosal C. acnes such as the face, in particular the neck, chin, nose, forehead, cheeks, shoulders, arms, back, torso; and/or the area of skin or mucous membrane whose skin barrier has been altered for example due to mechanical, chemical or biological action, such as by a sunburn (solar erythema), by the action of the razor, by the use of unsuitable or overly astringent cleaning products, by pollution, by the use of antibiotics, by allergens, etc.

These may include irritated areas, weakened areas, shaved areas, inflamed areas, scars and/or wounds.

The combination according to the invention comprises pullulan and a polysaccharide chosen from alginic acid and/or hyaluronic acid, their salts and/or derivatives. Advantageously the polysaccharide is propylene glycol alginate, sodium hyaluronate and/or mixtures thereof.

Pullulan is a natural polysaccharide (ose polymer) consisting of maltotriose units (a glucose trisaccharide), also known as α-1,4-α-1,6-glucan. The three glucose units that make up maltotriose are linked by an α-1,4 type sugar bond, while the maltotrioses are connected together by α-1,61 type sugar bonds. Pullulan is produced from starch by the fungus Aureobasidium pullulans and can be obtained from different Aureobasidium pullulans ferments. According to the present invention, pullulan can be used in its aqueous, optionally saline form. The pullulan derivatives which can be used in the context of the present invention are cosmetically and/or pharmaceutically acceptable derivatives, preferably dermatologically acceptable, that is to say they are non-toxic for administration to humans, in particular by application. topical and can be applied without risk and without causing an allergic or inflammatory reaction, particularly 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 chosen from trimethylsiloxysilylcarbamoyl pullulan and trimethylsilyl pullulan.

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

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-N-acetylglucosamine, 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 (conjugated base, salts and esters) are natural polysaccharides obtained from a family of brown algae: kelp or fucus. Alginate is a polymer formed of two monomers linked together: mannuronate or mannuronic acid, some of which are acetylated, and guluronate or guluronic acid. The connection is via beta 1-4. Alginates are used as thickeners, gelling agents, emulsifiers and stabilizers in a wide variety of industrial products. They are also known to have water retention properties. Preferably, in particular when the combination, the mixture of cosmetic and/or pharmaceutical ingredients or the cosmetic or pharmaceutical composition according to the invention contain a lot of salts, the alginic acid will be in the form of propylene glycol alginate, to facilitate the formulation and use of the combination and the compositions which contain it.

Particularly advantageously, pullulan is in association with alginic and/or hyaluronic acid as described in 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 one of the compounds", in particular pullulan, hyaluronic acid, alginic acid, succinic acid, lactic acid or sucrose, means all derivatives obtained by simple or multiple esterification of a primary or secondary alcohol function or an acid function of the compound, and presenting on the esterified part a carbon chain comprising from 1 to 6 carbon atoms, advantageously a linear or branched alkyl chain.

For the purposes of the present invention, the term "organomineral derivatives based on pullulan silicon, hyaluronic acid or alginic acid" means all derivatives which contain at least one silanol (-SiOH) and obtained by condensation of pullulan, hyaluronic acid or alginic acid with a molecule from the silane family.

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

The salts and derivatives of hyaluronic acid which can be used in the context of the present invention are 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, sulfated sodium hyaluronate and their mixtures. Advantageously it is sodium hyaluronate. In an advantageous embodiment, the hyaluronic acid derivatives are chosen from the derivatives usually used in cosmetics such as for example those chosen from esterified derivatives, in particular ascorbyl hyaluronate, benzyl hyaluronate, propylene glycol hyaluronate, acetylated sodium hyaluronate, sodium butyroyl hyaluronate 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 found 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 available commercially 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 which can be used in the context of the present invention are 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 glyceryl alginate or propylene glycol alginate, organomineral derivatives silicon of alginic acid, in particular siloxanetriol alginate or methylesilanol 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 found in the form of one of its salts. Advantageously it is sodium alginate. Advantageously, alginic acid, its salts or derivatives, in particular esterified or organominerals of silicon, have a weight average molecular weight, advantageously measured by steric exclusion chromatography, of 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 Ingredients. BASF, BAM, Penta Manufacturing Company, Vevy Europe.

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

In one embodiment of the present invention, the weight ratio of pullulan, or derivatives, and the polysaccharide (chosen from alginic and/or hyaluronic acid, salts or derivatives) 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 of hyaluronic acid, optionally in the form of salt or derivative in particular esterified, advantageously in the form of hyaluronate of sodium. Advantageously, for a quantity x (in g) of pullulan, or derivatives in particular esterified, the quantity of hyaluronic acid, salts or derivatives in particular esterified, will be between 0.001x and 100x. In particular, the ratio by weight of pullulan, 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 salt or derivative in particular esterified, advantageously in the form of alginate of propylene glycol. Advantageously, for a quantity x (in g) of pullulan, or derivatives in particular esterified, the quantity 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 in particular esterified/alginic 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, 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 salt or derivative in particular esterified, advantageously in the form of sodium hyaluronate , and alginic acid, optionally in the form of salt or derivative in particular esterified, advantageously in the form of propylene glycol alginate. It therefore includes these three compounds.

According to this third embodiment, advantageously, the combination according to the invention therefore comprises pullulan, sodium hyaluronate and propylene glycol alginate. Advantageously, the ratio by weight 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, again 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 preferably in the range 1/1/1 to 1/2/5. According to a preferential mode, this ratio is approximately 1/1/2, even more preferably it is 1/1/2.

According to this advantageous embodiment, said combination according to the invention forms a multistratified molecular network, corresponding to a molecular mesh with formation of hydrogen bonds, when the 3 pullulan compounds, optionally in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, salts or esterified derivatives are combined concomitantly, preferably in the form of a pre-mixture, 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, advantageously a ratio of 1/1/2.

In addition, this combination, in particular when it comprises the three compounds: pullulan, optionally in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, salts or esterified derivatives, has in fact an enhanced activity, so durable, particularly due to the formation of a molecular network when the 3 pullulan compounds, possibly in the form of derivatives, hyaluronic acid, salts or esterified derivatives, and alginic acid, salts or esterified derivatives, are combined concomitantly, preferably in the form of a pre-mixture, 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, advantageously a ratio of 1/1/2.

Succinic acid or butane 1,4 dioic acid (CAS 110-15-6) can be used in its acid molecule forms or in salts and/or derivatives, in particular esters, compatible with cosmetic and/or pharmaceutical use.

Among the salts of succinic acid, we can cite monosodium or disodium succinate.

Among the succinic acid derivatives, we can cite the cholesterol ester: cholesterol succinate.

Succinic acid can in particular be extracted from sugar cane by a biotechnological extraction process.

Preferably, succinic acid, optionally in the form of one of its salts and/or derivatives, is present in the combination at a content of 0.1% to 10%, preferably between 1% and 5%, again preferably 2% by weight of dry matter relative to the total weight of the combination.

According to a particularly advantageous embodiment of the invention, the succinic acid is present in the combination at a weight ratio of succinic acid, salts or derivatives/lactic acid, salts or derivatives lying in the range 1/2 to 1/ 5, preferably 1/3 to 1/4.

Lactic acid or 2-hydroxypropanoic acid can be used in its acid molecule forms or salts and/or derivatives in particular esters compatible with cosmetic and/or pharmaceutical use.

Among the lactic acid salts, we can cite sodium lactate, potassium lactate, magnesium lactate and zinc lactate.

Among the lactic acid derivatives, we can cite esterified derivatives, in particular isostearyl, stearyl and ethyl lactate.

Lactic acid can in particular be extracted from beets by a biotechnological extraction process.

Preferably, lactic acid, optionally in the form of one of its salts and/or derivatives, is present in the combination at a content of 1% to 15%, preferably between 3% and 9%, more preferably 6, 75% by weight of dry matter compared to the total weight of the suit

According to a particularly advantageous embodiment of the invention, lactic acid is present in the combination at a weight ratio of lactic acid, salts or derivatives/sucrose, salts or derivatives lying in the range 1/1 to 1/3 , preferably 1/1 to 1/2.

Sucrose, otherwise known as sucrose, can be used as is or in the form of a salt or a derivative compatible with cosmetic and/or pharmaceutical use.

Among the salts, we can cite the salts of sucrose octosulfate, in particular potassium sucrose octosulfate.

Among the derivatives, we can cite by way of example sucrose esters (or sucrose esters) in particular of fatty acids such as sucrose palmitate, sucrose cocoate, sucrose laurate, sucrose polystearate, sucrose polyoleate.

Sucrose can in particular be extracted from beets using a biotechnological extraction process.

Preferably, sucrose, optionally in the form of one of its salts and/or derivatives, is present in the combination at a content of 1% to 15%, preferably between 3% and 9%, more preferably 7.5 % by weight of dry matter relative to the total weight of the suit.

According to a particularly advantageous embodiment of the invention, succinic acid, lactic acid and sucrose are present in the combination at a ratio by weight of succinic acid, salts or derivatives / lactic acid, salts or derivatives / sucrose, salts or derivatives in the range 1/2/2 to 1/4/15, preferably 1/3/3 to 1/4/8.

For the purposes of the present invention, “combination” means the fact that the compounds (pullulan, alginic acid and/or hyaluronic acid, lactic acid, succinic acid and sucrose, optionally in the form of their respective salts and/or derivatives) are used together, preferably in the form of a premix. Advantageously, there is no covalent bond between the different compounds in the combination.

For the purposes of the present invention, “cosmetic use” means a non-therapeutic use, that is to say one which is not intended for therapeutic use and is intended and/or applied to a so-called healthy part of the body. , in particular on an area of the skin and/or mucous membranes, called healthy.

For the purposes of the present invention, “skin” means any part of the body and/or face, including the scalp.

For the purposes of the present invention, the term "mucous membrane(s)" means the mucous membranes on which C acnes are present, in particular the ocular mucosa, the nasal mucosa, the oral mucosa, in particular the labial oral mucosa and/or the gingival mucosa. , preferably, the ocular and/or oral mucosa, and even more preferably, the labial and/or ocular mucosa.

For the purposes of the present invention, the term “healthy skin and/or healthy mucous membranes” or “healthy tissue” means an area of skin, skin appendage or mucous membrane, to which the combination or mixture of ingredients or the composition according to the invention and which is said to be “non-pathological” by a dermatologist, that is to say not presenting any infection, in particular bacterial, scar, disease or skin condition such as candidiasis or dermatophytoses, impetigo, psoriasis, eczema, acne, ulcers, herpes or dermatitis, rosacea, telangiectasias, solar elastosis and/or pathology cutis laxa or sores or injuries, boils, pustules, papules, folliculitis, abscesses , sycosis, inflammation, erythema, particularly diaper, ecthyma, erysipelas, scar marks including pigment spots and/or acne scars. Advantageously, the combination according to the invention is not intended for atopic skin.

For the purposes of the present invention, the term "reduce and/or limit the virulence of a bacteria" is understood to mean at least partially inhibiting or limiting the adhesion to the skin and/or mucous membranes of this bacteria and/or inhibiting at least partially or limit the production of virulence factors such as the production of biofilm by this bacterium.

Adhesion to the skin and/or mucous membranes of C. acnes can be measured as described in Example 3.

Biofilm production by C. acnes can be measured as described in Example 2.

The effect of a product on the virulence of C. acnes is thus evaluated by measuring the adhesion to the skin and/or mucous membranes of C. acnes and/or by measuring the production of biofilm by C. acnes in the presence of the product tested and comparing the results to those obtained in the absence of the product tested. Preferably, the reduction in the virulence of C. acnes, preferably in the adhesion to the skin and/or mucous membranes of C. acnes and/or in the production of biofilm by C. acnes is at least 10%. , preferably at least 20%, more preferably 30% compared to the results obtained without treatment.

Here we mean “preventing and/or reducing unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes ” preventing the appearance of unsightly and/or unpleasant and/or uncomfortable manifestations and/or reducing them. the extent of healthy skin, healthy hair and/or healthy hair and/or healthy mucous membranes, and not prevent or treat a pathology. It is therefore a cosmetic use and not a therapeutic treatment.

Thus advantageously the cosmetic use according to the invention (and therefore non-therapeutic) is to prevent and/or reduce and/or eliminate unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes , in particular for 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 prevent and/or reduce the visibility of skin pores, and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity of the complexion of the skin and/or mucous membranes, for example by removing and /or reduction of redness and/or irregularities, and/or prevent and/or treat the sensation of heating of the skin and/or mucous membranes, and/or to prevent and/or reduce hair loss and/or hair, and/or to prevent and/or reduce dandruff.

In the sense of the present invention, “reducing the visibility of the skin pores” is understood to mean tightening the skin pores, that is to say reducing the opening diameter of the pores, and/or the density and/or the area of the pores at the surface of the skin, and/or prevent the dilation of skin pores. The combination according to the invention makes it possible to reduce the opening and/or density of pores on the surface of the skin.

The visibility of the pores of the skin can be demonstrated in vivo by an evaluation called “scoring” by a dermatologist on a predefined area after application of a composition comprising the combination according to the invention. It can also be demonstrated by an objective instrumental method by an image analysis making it possible to extract and quantify specific parameters from high-resolution photographs in cross-polarized configuration of the faces of volunteers before and after application of a composition comprising the combination according to the invention.

The density of skin pores can also be measured in vivo by imaging, in particular by the fringe projection technique, by measuring the so-called curvature parameter.

In a preferred embodiment of the invention, the combination according to the invention is in an effective quantity to reduce the visibility of the pores of the skin by at least 10%, preferably by at least 20%, after 28 days of application of a cream comprising the combination according to the invention, preferably formulated in the form of a cosmetic composition such as that described in the examples.

For the purposes of the present invention, the term “maintain and/or improve the homogeneity and/or radiance and/or luminosity of the complexion of the skin and/or mucous membranes”, prevent and/or reduce and/or treat complexion imperfections, such as redness or irregularities of the skin, make the complexion of the skin and/or mucous membranes more even and therefore less dull and more luminous, and/or reduce the reddish appearance of the skin in it giving a healthy and/or nourished appearance and therefore a healthy glow effect.

The measurement of the homogeneity, radiance and/or luminosity 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 crossed polarized configuration of the faces 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.

Advantageously, the term "reducing hair loss" means reducing the density of hair or body hair by at least 0.5%, preferably by at least 1%, and more preferably by at least 2%. telogen phase, that is to say in the falling phase. The measurement of the density of hair and/or hair in the telogen phase and in the anagen phase can be measured by in vivo measurement, by the phototrichogram technique, in the presence of the combination according to the invention or of a composition comprising it, in particular a formulation in the form of a shampoo, in comparison with the density of hair or hairs in the telogen and anagen phase measured without the combination according to the invention or without a composition comprising it.

In an advantageous embodiment, the combination is applied topically, advantageously on specific parts of the body chosen the body, the face, in particular the forehead, the cheeks, the nose the so-called "T" zone (forehead, nose and chin), neck and lip contour, scalp, shoulders, arms, back, torso, décolleté, ocular mucosa, nasal mucosa, oral mucosa, in particular the labial and/or oral mucosa the gingival mucosa, excessively cleaned areas and/or the area of skin or mucous membrane whose skin barrier has been altered for example due to mechanical, chemical or biological action, such as by sunburn (solar erythema) , 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...

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

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 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 cosmetic and/or pharmaceutical effectiveness. Active pharmaceutical ingredients correspond to active pharmaceutical ingredients. Categories and examples of cosmetic and/or pharmaceutical active ingredients are provided below.

For the purposes of the present invention, the term "suitable cosmetic or pharmaceutical vehicle" means that the composition or 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.

Advantageously, the combination according to the invention comprises, in particular is constituted by:
- pullulan or one of its derivatives, advantageously pullulan,
- hyaluronic acid, one of its salts or derivatives, advantageously sodium hyaluronate,
- alginic acid, one of its salts or derivatives, advantageously propylene glycol alginate,
- lactic acid, one of its salts or derivatives, advantageously lactic acid,
- succinic acid, one of its salts or derivatives, advantageously succinic acid and
- sucrose, one of its salts or derivatives, advantageously sucrose.

It therefore includes, in particular it is made up of, 6 ingredients.

The combination according to the invention, and preferably in the form of the 6 compounds (pullulan or its derivative, hyaluronic acid or its salt or derivative, alginic acid or its salt or derivative, lactic acid or its salt or derivative, succinic acid or its salt or derivative and sucrose or its 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 dermatological suitable for its formulation and/or its integration into a composition cosmetic or pharmaceutical, particularly dermatological. The combination according to the invention can also be used in a cosmetic or pharmaceutical composition, in particular dermatological, that is to say with an appropriate cosmetic or pharmaceutical vehicle, in particular suitable dermatological, and preferably intended for topical administration. Preferably, said combination according to the invention comprises, in particular consists of a mixture of the 6 compounds (pullulan or its derivative, hyaluronic acid or its salt or derivative, alginic acid or its salt or derivative, lactic acid or its salt or derivative , succinic acid or its salt or derivative and sucrose or its salt or derivative) preferably at a ratio lying in the range 1/1/1/1/1/1 to 1/10/10/300/100/300, and still preferably in the range 1/1/1/10/5/10 to 1/2/5/100/50/100, still preferably in the range 1/1/1/20/5/20 to 1/1/ 2/30/10/35, advantageously a ratio of 1/1/2/24/8/30.

According to a particular embodiment, the combination according to the invention, preferably the combination of the 6 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 for the mixture of cosmetic or pharmaceutical ingredients is and/or contains water.

The present invention further relates to a mixture of cosmetic or pharmaceutical ingredients intended to be incorporated into a cosmetic or pharmaceutical composition, said mixture comprising the combination according to the invention and a suitable cosmetic or pharmaceutical vehicle.

Advantageously, the combination according to the invention is included in the mixture of cosmetic or pharmaceutical ingredients, in particular dermatological, at a content of 0.001% to 30% by weight of dry matter relative to the total weight of the mixture of cosmetic or pharmaceutical ingredients. , more advantageously between 0.01 and 20% by weight, even more advantageously between 0.1 and 20% by weight, in particular between 0.25 and 20% by weight, more particularly between 1 and 20% by weight of dry matter relative to the total weight of the mixture of cosmetic or pharmaceutical ingredients, preferably in association with glycerin and/or xanthan gum and/or pentylene glycol, and/or caprylyl glycol and/or water, still advantageously xanthan gum and/or glycerin.

According to an advantageous mode, the mixture of cosmetic or pharmaceutical ingredients, in particular dermatological ingredients, comprises on the one hand:
- 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% in 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% in weight relative to the total weight of the mixture of ingredients and
- hyaluronic acid or one of its cosmetically or pharmaceutically acceptable salts or 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, advantageously between 0.001% and 5% by 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, very particularly 0.25% by weight relative to the total weight of the mixture of ingredients and/or
- alginic acid or one of its cosmetically or pharmaceutically acceptable salts or 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, 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 relative to the total weight of the mixture of ingredients,
And on the other hand :
- succinic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content of between 0.1 and 10% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 0.1 and 10 % by weight, more advantageously between 1 and 5% by weight, even more particularly 2% by weight relative to the total weight of the mixture of ingredients and
- lactic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content of between 1 and 15% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 3 and 9% by weight, even more particularly 6% by weight relative to the total weight of the mixture of ingredients
And
- sucrose or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content of between 1 and 15% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 3 and 9% by weight, even more particularly 7.5% by weight relative to the total weight of the mixture of ingredients.

According to a preferred mode, 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 between 1/1/1 and 1/10/10, preferably between 1/1/1 and 1/2/5, still preferably at a ratio of 1/1/2 .

In an advantageous embodiment, the mixture of cosmetic or pharmaceutical ingredients according to the invention further comprises xanthan gum and/or glycerin and/or water.

In particular, the mixture of cosmetic or pharmaceutical ingredients according to the invention is in liquid form.

Advantageously, the mixture of cosmetic or pharmaceutical ingredients according to the invention then contains a polar solvent, such as water, an alcohol, a polyol, a glycol, such as pentylene glycol and/or butylene glycol and/or or hexylene glycol and/or caprylyl glycol, or one of their mixtures, preferably a hydroglycolic mixture, more preferably containing a glycol chosen from hexylene glycol, pentylene glycol, caprylyl glycol and their mixtures, or glycerol.

Advantageously, the mixture of cosmetic or pharmaceutical ingredients contains pentylene glycol, in particular between 0.1 and 10%, preferably between 0.5 and 5%, more preferably between 1 and 3% by weight of pentylene glycol, relative to the weight total mixture of cosmetic ingredients.

Advantageously, the mixture of ingredients contains caprylyl glycol, in particular containing between 0.01 and 10%, preferably between 0.1 and 5%, more preferably between 0.3 and 1% by weight of caprylyl glycol, relative to the total weight. of the mixture of cosmetic ingredients.

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

The present invention further relates to a cosmetic or pharmaceutical composition intended for topical administration comprising the combination according to the invention or the mixture of cosmetic or pharmaceutical ingredients according to the invention and a suitable cosmetic or pharmaceutical vehicle.

In an advantageous embodiment, particularly if the mixture of cosmetic or pharmaceutical ingredients does not already contain them, the cosmetic or pharmaceutical composition according to the invention further comprises xanthan gum and/or glycerin and/or pentylene glycol and/or caprylyl glycol.

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 dermatological, intended for topical administration further comprising an appropriate 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 dermatological, in particular intended to be administered to a human being, preferably by topical application, preferably to the skin. 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 total dry matter relative to the total weight of the composition, between 0.0005% and 10%, plus advantageously between 0.005 and 10% by weight, even more advantageously between 0.005 and 5% by weight, in particular between 0.005 and 1% by weight, of total dry matter relative to the total weight of the composition. The cosmetic or pharmaceutical composition according to the invention, in particular dermatological, preferably also contains a cosmetic and/or pharmaceutical, in particular dermatological, vehicle and/or excipient.

According to an advantageous mode, the cosmetic or pharmaceutical composition, in particular dermatological, according to the invention comprises on the one hand:
- 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 a quantity between 0.001% and 5% in weight, more advantageously between 0.001 and 3% by weight, in particular between 0.002 and 0.1% by weight, more preferably between 0.002 and 0.075% by weight, and
- hyaluronic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives 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 preferably between 0.001 and 3% by weight, in particular between 0.002 and 0.1% by weight, more preferably between 0.002 and 0.075% by weight and/or
- alginic acid or one of its cosmetically or pharmaceutically acceptable salts or 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 0.001% and 5% by weight , more advantageously between 0.001 and 1% by weight, in particular between 0.005 and 0.1% by weight, even more particularly between 0.005 and 0.015% by weight,
And on the other hand :
- succinic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content of between 0.001 and 5% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 0.001 and 1% by weight, more advantageously between 0.001 and 0.1% by weight, even more advantageously between 0.01% and 0.05% by weight, even more particularly 0.04% by weight and
- lactic acid or one of its cosmetically or pharmaceutically acceptable salts or derivatives in a content of between 0.001 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 1% by weight, even more advantageously between 0.1 and 0.5% by weight, even more particularly 0.12% by weight and
- sucrose or cosmetically or pharmaceutically acceptable derivatives in a content of between 0.001 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 1% by weight, even more advantageously between 0.1 and 0.5% by weight, even more particularly 0.15% by weight.

According to a preferred mode, 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 presented in all the galenic forms conventionally used for topical application, such as liquid or solid forms or even in the form of liquid under pressure. . They may 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 pot or 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 bottle or in an 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, particularly in the form of a stick or in powders, notably 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, a hydrogel, a shower gel, a mask, a stick of a patch, or makeup 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, possibly 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 , stabilizing agents, emulsifiers, thickeners, gelling agents, film-forming polymers, solvents, fillers, bactericides, odor absorbers, mattifying 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 particularly suitable for topical use.

Preferably, the compositions according to the invention in the form of a mixture of cosmetic or pharmaceutical ingredients or cosmetic or pharmaceutical composition contain at least one other cosmetic or pharmaceutical active ingredient, in particular dermatological, and preferably from one to three ingredients cosmetic or pharmaceutical active ingredients, in particular dermatological, preferably having complementary properties on virulence factors and/or on unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes, in particular sebum secretion, the formation of blackheads and/or comedogenesis, the visibility of skin pores, the homogeneity and/or radiance and/or luminosity of the complexion of the skin and/or mucous membranes, the sensation of heating of the skin and/or mucous membranes, loss of hair and/or body hair and/or the appearance of dandruff.

It may in particular be one or more other ingredients active on the skin and/or mucosal microbial flora and/or active on the barrier function of the skin, in particular moisturizing and/or soothing active ingredients, including an oligosaccharide obtained by enzymatic synthesis. marketed by the company Solabia under the name BioEcolia™ or a complex of alpha-glucooligosaccharides marketed by the same company under the name Ecoskin™, an extract of Alisma plantago-aquatica, an extract of Argania spinosa ( Lipofructyl™ Argan ), a mixture of ceramides (Sphingoceryl™ VEG), purifying extracts of Boldo (Betapur™), products based on inulin or fructooligosaccharides, extracts of bifidobacteria or even an extract of Orthosiphon stamineus to fight against the skin oily (MAT-XS™ Bright), a natural honey extract marketed by the applicant under the name Melhydran™ for its moisturizing property, a flax extract marketed under the name Oligolin™ by the applicant, a biotechnologically modified yeast extract and marketed by the applicant under the name Relipidium™, a root extract of Pueraria lobata marketed under the name Inhipase™ by the applicant, a beta-glucan derivative from baker's yeast marketed by Mibelle under the name CM-Glucan Forte™ and/or an extract of Mirabilis jalapa marketed under the name Pacifeel™ by Sederma.

These may be cosmetic ingredients having a complementary effect such as those chosen from salicylic acid, niacinamide, zinc gluconate, an extract of Bixa orellana seeds (for example Bix-Activ™) and/or N -methyl glycine (e.g. Scalposine™).

The present invention further relates to the cosmetic use of the combination according to the invention or of the mixture of cosmetic ingredients according to the invention or of the cosmetic composition according to the invention to limit and/or reduce the virulence of Cutibacterium acnes on the skin and/or mucous membranes, in particular by at least one of the following mechanisms:
- by inhibiting or limiting the adhesion of Cutibacterium acnes ;
- by inhibiting or limiting the production of Cutibacterium acnes virulence factors such as biofilm.

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 of a cosmetic composition according to the present invention, to limit and/or reduce the virulence of Cutibacterium acnes , in particular the formation of biofilm, in order to prevent and/or reduce the uncomfortable and/or unpleasant and/or unsightly manifestations of the virulence factors of Cutibacterium acnes .

Advantageously, the cosmetic use according to the invention (and therefore non-therapeutic) is to prevent and/or reduce and/or eliminate unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes , 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, prevent and /or reduce the visibility of skin pores and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity 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 to prevent and/or reduce hair loss and/or to prevent and/or reduce dandruff.

The combination or mixture of cosmetic or pharmaceutical, particularly dermatological, ingredients according to the invention is topically acceptable.

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

The combination according to the invention, in particular in the form of a cosmetic or pharmaceutical composition, in particular dermatological, is therefore particularly suitable for the care and/or treatment of skin and/or mucous membranes presenting a large quantity of cutaneous C. acnes and /or mucosal such as the face in particular the mention, the forehead, the cheeks and/or the contour of the lips, the shoulders, the arms, the back, the torso, the neckline, the ocular, nasal, oral mucosa, in particular the labial oral mucosa and/or gingival mucosa, excessively cleaned areas, and/or the area of skin or mucosa whose skin barrier has been altered for example due to mechanical, chemical or biological action, such as by a sunburn (solar erythema), 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.... 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 to limit and/or reduce the mucosal virulence of Cutibacterium acnes , advantageously to prevent and/or reduce and/or suppress the unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of Cutibacterium acnes , in particular to maintain and/or increase and/or improve the homogeneity and/or radiance and/or luminosity of the complexion of the mucous membranes and /or prevent and/or treat the feeling of heating of the mucous membranes.

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, preferably chosen from the body, the face, in particular the forehead, cheeks, chin, nose, the so-called “T” zone (forehead, nose and chin), neck and lip contour, scalp, shoulders, arms, back, torso, décolleté , the ocular mucosa, the nasal mucosa, the oral mucosa, in particular the labial oral mucosa and/or the gingival mucosa, excessively cleaned areas and/or the area of skin or mucosa whose skin barrier has been altered, for example due to from a mechanical, chemical or biological action, such as by a sunburn (solar erythema), by the action of the razor, by the use of unsuitable or too astringent cleaning products, by pollution, by the use antibiotics, allergens, etc.

The present invention further relates to the combination according to the invention, advantageously in the form of a mixture of pharmaceutical ingredients or in the form of a pharmaceutical composition, in particular dermatological, according to the present invention for its use as a pharmaceutical active ingredient, particularly dermatological, in particular in the treatment and/or prevention and/or reduction of the occurrence of pathologies due to the virulence of C. acnes, advantageously involving an increase in biofilm secretion and/or an increase in adhesion of C. acnes , advantageously pathologies chosen from the group consisting of bacterial infections of the skin and/or mucous membranes, pustules, papules, boils, folliculitis, abscesses, acne, in particular superinfected, wounds in particularly superinfected, inflammation of the skin and/or mucous membranes, and/or in the prevention of scarring including pigment spots and/or acne scars.

Finally, the present invention relates to a cosmetic treatment method, characterized in that it comprises the application to at least one affected area of the skin and/or mucous membranes of the face and/or body, of the combination according to the present invention or a cosmetic composition or a mixture of cosmetic ingredients comprising, as active agent, the combination according to the invention as defined above, to prevent and/or reduce and/or eliminate unsightly manifestations and /or unpleasant and/or uncomfortable due to the virulence of Cutibacterium acnes in particular the formation of biofilm , in particular to prevent and/or reduce and/or delay the secretion of sebum and its unsightly and/or unpleasant and/or uncomfortable manifestations, more particularly to prevent and/or reduce and/or delay the formation of blackheads and/or comedogenesis, and/or prevent and/or reduce the visibility of skin pores and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity 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 to prevent and/or reduce hair loss and/or body hair, and/or to prevent and/or reduce dandruff.

The present invention further relates to a method of cosmetic care for preventing and/or reducing and/or eliminating unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of Cutibacterium acnes , in particular the formation of biofilm , in particular to prevent and/or reduce and/or delay the secretion of sebum and its unsightly and/or unpleasant and/or uncomfortable manifestations, more particularly to prevent and/or reduce and/or delay the formation of blackheads and/or comedogenesis, and/or or prevent and/or reduce the visibility of skin pores and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity of the complexion of the skin and/or mucous membranes, and/or prevent and/or or treat the sensation of heating of the skin and/or mucous membranes, and/or to prevent and/or reduce hair loss, and/or to prevent and/or reduce dandruff, characterized in that that it comprises the application to at least one area concerned of the skin and/or mucous membranes of the face and/or body, of the combination according to the present invention or of a cosmetic composition or a mixture of ingredients cosmetics comprising, as active agent, the combination according to the invention as defined above. In particular, the method comprises the selection of an area of the skin and/or mucous membranes for which it is necessary to prevent and/or reduce and/or eliminate the unsightly and/or unpleasant and/or uncomfortable manifestations due to virulence. of Cutibacterium acnes, more particularly the formation of biofilm, in particular to delay the secretion of sebum and its unsightly and/or unpleasant and/or uncomfortable manifestations, more particularly to reduce and/or delay the formation of blackheads and/or the comedogenesis, and/or prevent and/or reduce the visibility of skin pores and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity of the skin tone and/or mucous membranes, and/or to prevent and/or treat the sensation of heating of the skin and/or mucous membranes, and/or to prevent and/or reduce hair loss, and/or to prevent and /or reduce dandruff, before application, of the combination according to the present invention or of a cosmetic composition or of a mixture of cosmetic ingredients comprising, as active agent, the combination according to the invention such as defined previously, in particular in an effective quantity.

Advantageously the area concerned of the skin and/or mucous membranes of the face or body is chosen from all or part of the human body, preferably chosen from the body, the face, in particular the forehead, the cheeks, the chin, the nose, the so-called “T” area (forehead, nose and chin), neck and lip contour, scalp, shoulders, arms, back, torso, neckline, ocular mucosa, nasal mucosa, oral mucosa, in particular the labial oral mucosa and/or the gingival mucosa, excessively cleaned areas and/or the area of skin or mucosa whose skin barrier has been altered for example due to mechanical, chemical or biological action, such as by a sunburn (solar erythema), 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 further relates to a method of treatment and/or prevention and/or reduction of the occurrence of pathologies due to the virulence of C acnes , advantageously involving an increase in the secretion of biofilm and/or an increase in the adhesion of C. acnes , advantageously pathologies chosen from the group consisting of bacterial infections of the skin and/or mucous membranes, pustules, papules, boils, folliculitis, abscesses, acne, in particular superinfected, wounds in particular superinfected, inflammation of the skin and/or mucous membranes, and/or in the prevention of scar marks in particular 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, of an effective quantity of the combination according to the present invention or of a pharmaceutical composition or of a mixture of pharmaceutical ingredients comprising as active agent, the combination according to the invention as defined above.

Other aims, characteristics and advantages of the invention will become clear to those skilled in the art following reading of the explanatory description which refers to examples which are given only by way of illustration and which cannot be relied upon. in any way limit the scope of the invention.

The examples form an integral part of the present invention and any characteristic appearing new compared to any state of the prior art from the description taken as a whole, including the examples, is an integral part of the invention in its function and in 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 atmospheric pressure.

Examples Example 1: Combination according to the invention

The combination according to the invention was obtained by simple mixing of the following compounds as indicated in Table 1 below:

Name Quantity % by weight/total weight of the mixture Osmotic water QSP Propylene glycol alginate 0.50 Hyaluronic acid 0.25 Pullulan 0.25 Lactic acid (purity 90%) 6.75 Succinic acid 2.00 Sucrose 7.50 Glycerin 12.50 xanthan gum 0.50 Example 2: Evaluation of the inhibition of the product according to the invention on biofilm formation by C acnes .

Protocol:

Cutibacterium acnes was taken from human skin (face) and type I typed using the MLST (MultiLocus Sequencing Typing) method (bacteria called IA2 from the company Biofilm Control).

It was grown on an agar plate under anaerobic conditions.

The product according to example 1 was tested and compared to two comparison products called C1 and C2 of the following composition:

Product C1 corresponds to the product according to example 1 devoid of the 3 compounds: succinic acid, lactic acid and sucrose and whose composition is indicated in the following table 2:

Name Quantity % by weight/total weight of the mixture Osmotic water QSP Propylene glycol alginate 0.50 Hyaluronic acid 0.25 Pullulan 0.25 Glycerin 12.50 xanthan gum 0.50

Product C2: corresponds to the 3 compounds removed from the product of Example 1 (and absent from product C1) and whose composition is indicated in the following Table 3:

Name Quantity % by weight/total weight of the mixture Osmotic water QSP Lactic acid (purity 90%) 6.75 Succinic acid 2.00 Sucrose 7.50

Each product tested was added to the well of a 96-well plate at 1% by volume relative to the total volume of the culture medium and the product tested. Each product was tested in triplicate then the plates were kept overnight at -20°C then the BioFilm Ring Test (BRT ^® ) was carried out (Biofilm Control). This test is based on the ability of bacteria to secrete exopolysaccharides present in the biofilm, which will immobilize the magnetic particles.

C. acnes IA2 shows biofilm formation from 48 hours of incubation. Thus, the BRT was carried out at 56 hours.

When the microplates were at room temperature, the initial bacterial suspension was prepared in BHI (Brain Heart Infusion) type culture medium, seeded at 10 ⁶ CFU/mL estimated by absorbance measurement (OD 600nm) and each well was filled with magnetic beads (TON004) at 10 µL/mL. Negative controls were prepared by mixing BHI with TON004 (10 µL/mL). Controls were also present in parallel to evaluate the mobility of the microbeads in the presence of the ingredients alone.

The microplates were incubated under anaerobic conditions at 37°C. After 56 hours, a contrast liquid was added to each well and the microplate was magnetized for 1 min on the Block Test. The microplate was then scanned and analyzed with BFC Elements 3.0 software. When the biofilm is formed the beads cannot move into the well. This corresponds to a biofilm formed at 100%. In the presence of ingredients inhibiting the formation of biofilm, the beads will be able to aggregate in the center of the well. The rate of beads aggregating in the center of the well corresponds to the percentage of inhibition of biofilm formation.

The results are presented as percentage of C. acnes biofilm formation. The positive control corresponds to 100% biofilm formed by the C. acnes bacteria alone.

The results are presented in table 4: n=3; Avg. denotes the average; SEM designates the deviation from the mean.

Positive control In the presence of the product tested at 1% (v/v) Product according to example 1 Product C1 Product C2 Avg. 100 66 86.1 100.0 S.E.M. 1.5 3.8 7.2 0.0

The viability of C acnes was checked at 56 hours in the presence of the product according to example 1 at 1% (v/v) and no impact on the viability of C acnes was noted. The product according to Example 1 therefore does not inhibit the growth of C. acnes .

Conclusion: The product according to the invention at the doses tested inhibited very significantly (t test performed versus the Positive Control with a significance threshold p<0.001) the formation of C. acnes biofilm in a synergistic manner with regard to its compounds tested separately.
Example 3: Evaluation of the inhibition of adhesion on C acnes by the product according to the invention.

Protocol

The C. acnes bacteria deposited in culture under the number ATCC6919 (Phylotype IA1) was cultivated anaerobically for 72 hours at 37°C in non-selective culture medium (Schaedler) in the absence (called “Untreated control”) or in the presence of the Product according to Example 1 at 1% by volume relative to the total volume (culture medium + Product according to Example 1).

The cultures were then centrifuged and the pellets were resuspended in alkaline phosphate buffer (PBS 1X Mg Ca) in the absence (called “Untreated Control”) or in the presence of the Product according to example 1 at 1% by volume relative to the total volume (culture medium + Product according to example 1). The optical density OD at 600nm was adjusted to 0.8 per well (in n=11)

The cultures were placed anaerobically for 6 hours at 37°C to allow bacterial adhesion. Then, syto9 labeling was carried out to allow observation of adherent bacteria under a confocal microscope (excitation/emission: 485/498nm).

Biomass analysis was carried out with ComStat2 software. It is a volume calculation in µm ³ /µm ² (corresponds to the biomass (in µm ³ ) divided by the surface area in µm ² ).

Counting the volume of the Biomass in µm ³ /µm ² SEM T-test vs untreated control.

Results are presented in the following table 5: n=11; Avg. denotes the average. SEM designates the deviation from the mean

The statistical test used is the t test performed versus the untreated control with a significance threshold of p<0.01. S denotes a significant deviation from the mean.

Counting the volume of Biomass in µm ³ / µm ² S.E.M. T-test vs. Untreated Control Untreated control 2501 245 Product according to example 1 to 1% (w/w) 1409 269 S
(p<0.01)

Conclusion: The product according to the invention inhibits the adhesion of C. acnes without impact on the viability of C. acnes .
Example 4: Mixture of cosmetic or pharmaceutical ingredients according to the invention containing the combination according to the invention

. A mixture of cosmetic or pharmaceutical ingredients having the formulation indicated in Table 6 below in percentage by weight is prepared.

Denomination Quantity in % Propylene glycol alginate 0.50 Pentylene glycol 2.00 Lactic acid (purity 90%) 6.75 Sucrose 7.50 Succinic acid 2.00 Sodium hyaluronate 0.25 Caprylyl glycol 0.50 Pullulan 0.25 Glycerin 12.50 Xanthan gum 0.50 Water QSP

Pentylene glycol, caprylyl glycol, glycerin, lactic acid, succinic acid and sucrose are first dissolved in water. The polymers (hyaluronic acid, pullulan, propylene glycol alginate and xanthan gum) are then added to this aqueous solution and the mixture obtained is kept stirring until a homogeneous product is obtained.
Example 5: Composition according to the invention in the form of a body and/or face lotion

Phase Denomination Quantity (% by total weight) HAS Water QSP HAS Disodium EDTA 0.05 HAS 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 4 comprising the combination according to the invention 2.00 D Water 1.00 D Sodium hydroxide (30% in solution) 0.10 E Blend of phenoxyethanol, chlorphenesin, benzoic acid, butylene glycol, sorbic acid (Germazide™ PBS) 1.25 F Blend of polyacrylate-X, isohexadecane and polysorbate 60 (Sepigel™ SMS 60) 4.00

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 (17)

Combination including:
- pullulan or one of its derivatives, advantageously pullulan,
- 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
- lactic acid, one of its salts or derivatives,
- succinic acid, one of its salts or derivatives and
- sucrose, one of its salts or derivatives. Combination according to claim 1, characterized in that the polysaccharide is propylene glycol alginate, sodium hyaluronate and/or mixtures thereof. Combination according to any one of claims 1 or 2, characterized in that the weight ratio of pullulan, or derivatives and the polysaccharide is in the range 1/0.002 and 1/200. Combination according to any one of claims 1 to 3 comprising:
- pullulan or one of its derivatives, advantageously pullulan,
- hyaluronic acid, one of its salts or derivatives, advantageously sodium hyaluronate,
- alginic acid, one of its salts or derivatives, advantageously propylene glycol alginate,
- lactic acid, one of its salts or derivatives, advantageously lactic acid,
- succinic acid, one of its salts or derivatives, advantageously succinic acid and
- sucrose, one of its salts or derivatives, advantageously sucrose. Combination according to any one of claims 1 to 4, characterized in that the weight ratio pullulan or one of its derivatives, hyaluronic acid or its salt or derivative, alginic acid or its salt or derivative, lactic acid or its salt or derivative , succinic acid or its salt or derivative and sucrose or its salt or derivative is in the range 1/1/1/1/1/1 to 1/10/10/300/100/300, and again preferably in the range 1/1/1/10/5/10 to 1/2/5/100/50/100, still preferably in the range 1/1/1/20/5/20 to 1/1/2/30/10 /35, advantageously a ratio of 1/1/2/24/8/30. Mixture of cosmetic or pharmaceutical ingredients intended to be incorporated into a cosmetic or pharmaceutical composition, said mixture comprising the combination according to any one of claims 1 to 5 and a suitable cosmetic or pharmaceutical vehicle. Mixture of cosmetic or pharmaceutical ingredients according to claim 6, characterized in that it comprises the combination in a content of between 0.001 and 30% by weight of dry matter relative to the total weight of the mixture of ingredients, advantageously between 0. 1 and 20% by weight, preferably in combination with glycerin and/or xanthan gum and/or pentylene glycol and/or caprylyl glycol. Cosmetic or pharmaceutical composition intended for topical administration comprising the combination according to any one of claims 1 to 5 or the mixture of cosmetic or pharmaceutical ingredients according to any one of claims 6 or 7 and a suitable cosmetic or pharmaceutical vehicle . Composition according to claim 8, characterized in that it comprises the combination in a content of between 0.0001% and 20% by weight of dry matter relative to the total weight of the composition, advantageously between 0.005 and 5% by weight. Cosmetic use of the combination according to any one of claims 1 to 5 or of the mixture of cosmetic ingredients according to any one of claims 6 or 7 or of the cosmetic composition according to any one of claims 8 or 9 to limit and /or reduce the virulence of Cutibacterium acnes on the skin and/or mucous membranes, in particular by at least one of the following mechanisms:
- by inhibiting or limiting the adhesion of Cutibacterium acnes ;
- by inhibiting or limiting the production of Cutibacterium acnes virulence factors such as biofilm. Cosmetic use according to claim 10 to prevent and/or reduce and/or eliminate unsightly and/or unpleasant and/or uncomfortable manifestations due to the virulence of C. acnes, in particular to prevent and/or reduce and/or delay secretion of sebum and its unsightly and/or unpleasant and/or uncomfortable manifestations, more particularly to prevent and/or reduce and/or delay the formation of blackheads and/or comedogenesis, and/or prevent and/or reduce the visibility of pores skin, and/or maintain and/or improve the homogeneity and/or radiance and/or luminosity 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 to prevent and/or reduce hair loss, and/or to prevent and/or reduce dandruff. Cosmetic treatment method characterized in that it comprises the application to at least one affected area of the skin and/or mucous membranes of the face and/or body, of the combination according to any one of claims 1 to 5 or of the mixture of cosmetic ingredients according to any one of claims 6 or 7 or of the cosmetic composition according to any one of claims 8 or 9, to limit or reduce the virulence of Cutibacterium acnes on the skin and/or mucous membranes, in particular by at least one of the following mechanisms:
- by inhibiting or limiting the adhesion of Cutibacterium acnes ;
- by inhibiting or limiting the production of Cutibacterium acnes virulence factors such as biofilm. Cosmetic treatment method according to claim 12 to prevent and/or reduce unsightly and/or unpleasant/or uncomfortable manifestations due to the virulence of C. acnes, in particular to prevent and/or reduce and/or delay the secretion of sebum and its unsightly and/or unpleasant and/or uncomfortable manifestations, more particularly to prevent and/or reduce and/or delay the formation of blackheads and/or comedogenesis, and/or reduce the visibility of skin pores, and/or maintain and /or improve the homogeneity, radiance and/or luminosity of the complexion of the skin and/or mucous membranes, and/or prevent and/or treat the feeling of heating of the skin and/or mucous membranes, and/ or to prevent and/or reduce hair loss, and/or to prevent and/or reduce dandruff Cosmetic treatment method according to any one of claims 12 or 13, characterized in that the area concerned of the skin and/or mucous membranes of the face or body is chosen from all or part of the human body, in particular the forehead, the cheeks, chin, nose, the so-called “T” zone (forehead, nose and chin), neck and lip contour, scalp, shoulders, arms, back, torso, décolleté, the ocular mucosa, the nasal mucosa, the oral mucosa, in particular the labial oral mucosa and/or the gingival mucosa, excessively cleaned areas and/or the area of skin or mucosa whose skin barrier has been altered, for example due to 'a mechanical, chemical or biological action, such as by a sunburn, 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. Combination according to any one of claims 1 to 5 or mixture of pharmaceutical ingredients according to any one of claims 6 or 7 or pharmaceutical composition, in particular dermatological, according to any one of claims 8 or 9 for its use as an active ingredient pharmaceutical, in particular dermatological, in particular for preventing and/or treating pathologies due to the virulence of C. acnes, advantageously involving an increase in the secretion of biofilm and/or an increase in the adhesion of C. acnes . Combination or mixtures of pharmaceutical ingredients or pharmaceutical composition for its use according to claim 15, characterized in that the pathologies are chosen from the group consisting of bacterial infections of the skin and/or mucous membranes, pustules, papules, boils, folliculitis, abscesses, acne, in particular superinfected, wounds in particular superinfected, inflammation of the skin and/or mucous membranes, and/or in the prevention of scarring, in particular pigment spots and/or scars. 'acne. Combination according to any one of claims 1 to 5 or mixture of pharmaceutical ingredients according to any one of claims 6 or 7 or pharmaceutical composition for its use to prevent and/or treat acne, in particular superinfected, and/or acne scars.