FR3101776A1 - New cosmetic use of N-methylglycine to increase the diversity of skin microbial flora - Google Patents

Abstract

New cosmetic use of N-methylglycine to increase the diversity of skin microbial flora The invention relates to the cosmetic use of N-methylglycine as a cutaneous prebiotic, to increase the diversity of the cutaneous microbial flora, to prevent and / or decrease the fall of the cutaneous appendages, in particular of the hair, and / or to prevent the 'appearance and / or decrease dandruff. Another object relates to a cosmetic care process comprising the topical application of N-methylglycine or of a composition comprising, to increase the diversity of the cutaneous microbial flora, to decrease the fall of the cutaneous appendages and / or to prevent the appearance and / or reduce dandruff. Yet another object relates to N-methylglycine or a pharmaceutical composition comprising for its use for reducing itching and / or skin irritation, and / or for preventing and / or reducing the sensitivity of the scalp.

Description

New cosmetic use of N-methylglycine to increase the diversity of the cutaneous microbial flora

The present invention relates to a new use of N-methylglycine for increasing the diversity of the cutaneous microbial flora, advantageously of the scalp.

Just like the face and the body, the skull has its own skin: the scalp. Often overlooked because it is not very visible, it is the seat of the appearance of inconveniences that can manifest themselves in the form of dandruff, accompanied by itching and irritation. Scalp sensitivity can also occur without necessarily being related to a dandruff component. Scalp sensitivity is characterized by the tingling sensation on the scalp associated or not with a painful sensation following exposure to various chemical or thermal stimuli. The scalp can also suffer from biological disturbances leading to excessive or premature hair loss. These inconveniences involve various biological mechanisms correlated with a disturbance of the cutaneous microbial flora, in particular of the scalp.

With regard to dandruff in particular, they can concern different types of scalp (dry, oily, young or adult subjects). The origin of dandruff lies in an imbalance of the microbial flora of the scalp since the scalp displaying dandruff shows a higher proportion of bacteria of the genus staphylococcus .

On the other hand, discomforts such as stinging, itching, pain and burning were significantly correlated with the presence of certain bacteria from the Bacteroides group, Propionibacterium and Chryseobacterium . Additionally, exotoxins from staphylococci such as Staphylococcus aureus can trigger the expression of mediators involved in itchy scalp.

Regarding the sensitive scalp, it is correlated with an increase in sebum as well as an increase in Propionibacterium and a decrease in bacterial diversity.

Finally, hair loss has been positively correlated with sensitive scalp. Thus, the field of cosmetics is in constant demand for active ingredients capable of fighting against dandruff as well as the irritation and itching that often accompany it.

The applicant discovered quite surprisingly that N-methylglycine, also called sarcosine, had the capacity to increase the diversity of the cutaneous microbial flora, making it possible to prevent and/or reduce hair loss, and/or to prevent the appearance and/or reduce dandruff, and/or reduce itching and/or skin irritation, in particular of the scalp.

N-methylglycine is a methylated derivative of glycine (CAS No. 107-97-1), with molecular formula C ₃ H ₇ NO ₂ , with molar mass 89.09 g/mol and with formula:

N-methylglycine is marketed under the name MAT-XS™ by the applicant, for its use in particular in the reduction of sebum production, the reduction of imperfections linked to hyperseborrhoea and the reduction in the visibility of the pores of the skin.

N-methylglycine derivatives are known to be used in cosmetic compositions for the scalp, in particular as anionic detergents, including cosmetic compositions for anti-dandruff use.

However, to the applicant's knowledge, no prior art discloses or suggests a cosmetic use of N-methylglycine for its effects on increasing the diversity of the cutaneous microbial flora, in particular that of the scalp, to prevent and / or reduce hair loss, and / or to prevent the appearance and / or reduce dandruff, or to reduce itching and / or skin irritation, in particular of the scalp, and / or to prevent and / or reduce the skin sensitivity, especially of the scalp.

The advantage of this molecule is that it is already known to be formulated easily in cosmetic compositions, in particular compositions for the scalp, without any topical allergic risk. It is also readily available commercially.

Thus a first object of the invention is the non-therapeutic cosmetic use of N-methylglycine to increase the diversity of the cutaneous microbial flora, advantageously of the scalp. A second object is the cosmetic use of N-methylglycine in a cosmetic composition comprising at least one cosmetically acceptable excipient. A third object concerns a cosmetic care process comprising the topical application of N-methylglycine or of a composition comprising it on all or part of the scalp and/or the skin appendages. A final object concerns N-methylglycine or a pharmaceutical composition, advantageously dermatological, comprising it for its use to reduce itching and/or skin irritation, advantageously irritation of the scalp.

A first object therefore concerns the non-therapeutic cosmetic use of N-methylglycine to increase the diversity of the cutaneous microbial flora, advantageously of the scalp.

"Cosmetic use" means a non-therapeutic, non-pharmaceutical or dermatological use, i.e. which does not require therapeutic treatment and intended for healthy skin. "Healthy skin" means skin qualified as non-pathological by a specialist in the field, a dermatologist, i.e. showing no infection, scar, disease or skin condition such as candidiasis, impetigo, psoriasis, eczema, acne or dermatitis, wounds or injuries and/or other dermatoses and/or androgenic alopecia.

A subject of the present invention is also the non-therapeutic cosmetic use of N-methylglycine as a skin prebiotic. Indeed, N-methylglycine makes it possible to increase the growth and/or the activity of the cutaneous microbial flora, in particular the strains chosen from those of the genera:
- Streptococcus in particular chosen from Streptococcus salivarus , Streptococcus australis, Streptococcus parasanguinis and Streptoccus infantis .
- Staphyloccocus especially S. pasteuri and S. warneri
- Rothia, in particular Rothia aeria ,
- Actinomyces, especially A. odontoliticus ,
- Veillonella, especially V. Parvula .

Within the meaning of the present invention, the term “skin prebiotic” means any product which increases the growth and/or the activity of bacteria of the skin microbiota, preferentially the aforementioned strains, preferentially S . salivarus , S. pasteuri , S. parasanguinis , V. parvula , S. australis, S. warneri , Rothia aeria , S. infantis , Actinomyces odontoliticus .

This growth and/or activity of the bacteria of the skin microbiota can be measured according to conventional methods in the field.

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

Alternatively, it is also possible to measure the change in the relative content of bacteria in the presence of N-methylgycine in situ, in particular according to the method described in Example 2a.

. The activity of the strains of microorganisms can be measured according to conventional methods for those skilled in the art, such as, for example, by studying the production of metabolites of the cutaneous microflora, in particular organic acids such as lactic acid and acetic acid. bacteria.

N-Methylglycine is a topically acceptable ingredient. "Topically acceptable" means an ingredient suitable for topical application, non-toxic, non-irritating to the skin, not inducing an allergic response, which is not chemically unstable.

The use of this molecule can be orally or topically. Advantageously, it is applied topically. Topical means the direct local application and/or vaporization of the ingredient on the surface of the skin.

The ingredient can be applied topically to all or part of the body, advantageously chosen from the legs, feet, armpits, hands, thighs, stomach, décolleté, neck, arms, torso, back, the face including the forehead, the cheeks, the nose, the temples, the T-zone (forehead, nose and chin) and/or the scalp, more advantageously the scalp.

Within the meaning of the invention, the skin includes the scalp.

By "cutaneous appendages" is meant body hair, hair, nails, and advantageously hair.

The term "cutaneous microbial flora" means the beneficial and mutualist commensal strains of bacteria and/or yeast and/or fungi and/or the pathogenic opportunistic strains, in particular the beneficial and mutualist commensal strains chosen from:
- the Phylum of actinobacteria comprising the Corynebacteriacease family, in particular the Corynebacterium genus, the bacteria of the Micrococcaceae family, in particular the Micrococcus and/or Kocuria genera, the bacteria of the Propionibacteriaceae family with the Propionibacterium or Cutibacterium genus, the bacteria of the Brevibacteriaceae family including the Brevibacterium genus.
- bacteria from the Phylum of Proteobacteria, including those of the Rhodobacteriaceae family, in particular the Paracoccus and/or Amaricoccus genera, those of the Acetobacteraceae family, in particular the Roseomonas genus, of the Caulobacteraceae family, in particular the Brevundimonas genus, of the Moraxellaceae in particular the genera Enhydrobacter and or Acinetobacter .
- Bacteria of the Phylum firmicutes comprising bacteria of the family Staphylococcaceae with the genus Staphylococcus , in particular Staphylococcus hominis, S. warneri, S. capitis, S. epidermidis, S. pasteuri, S. saprophyticus preferentially S. epidermidis , those of the family Streptococcaceae with the genus Streptococcus in particular Streptococcus salivarus, S. australis, those of the family Bacilliaceae with the genus Bacillus , those of the genus Veillonella and those of the Lactobacilliaceae in particular the genus Lactobacillus .

Preferably, the beneficial and mutualist cutaneous commensal bacteria are chosen from the genus Corynebacterium , the genus Micrococcus , the genus Kocuria , the genus Propionibacterium , the genus Brevibacterium , the genus Paracoccus , the genus Amaricoccus , the genus Roseomonas , the genus Brevundimonas , the genus Enhydrobacter , the genus Acinetobacter , S. hominis, S. warneri, S. capitis, S. epidermidis, S. pasteuri, S. saprophyticus, preferentially S. epidermidis , the genus Lactobacillus , the genus Lactobacillus and mixtures thereof.

The cutaneous pathogenic opportunistic strains are chosen from those:
-of the Phylum of proteobacteria, of the Enterobacteriaceae family, in particular the Pantoea genus, and/or of the Pseudomonaceae family, in particular of the Pseudomonas genus.
- from the firmicutes phylum with the Staphylococcaceae family, in particular the Staphylococcus genus, in particular Staphylococcus aureus , and with the Streptococcaceae family, in particular Streptococcus pyogenes .
- of the Actinobacteria phylum comprising the Proprionibacteriaceae family, in particular Propionibacterium acnes ( Cutibacterium acnes) .

Preferably, the cutaneous pathogenic opportunity strains are chosen from the genus Pantoea , the genus Pseudomonas , S. aureus , S. pyogenes and P. acnes . According to a preferential mode, the cutaneous pathogenic opportunistic strains are S. aureus and/or P. acnes .

Within the meaning of the invention, the cutaneous microbial flora, in particular of the scalp, therefore includes yeasts, among which the species of the genus Malassezia , and advantageously the species M. restricta .

The term "increase the diversity of the cutaneous microbial flora" means promoting the appearance of new bacteria and/or strains of bacteria constituting the cutaneous microbial flora. In an advantageous embodiment of the invention, it is the appearance of at least 10% of new strains, advantageously of at least 20%, after 28 days of application of a formulation comprising of N-methylglycine, in comparison with the population of strains detected after 28 days of application of the same formulation without N-methylglycine, as described in example 2. In a particularly advantageous embodiment, it is it is the appearance of at least 10% of new strains, advantageously of at least 20% of new beneficial commensal strains, again advantageously chosen from Streptococcus salivarus, Staphylococcus pasteuri, Rhotia mucilaginosa, Streptococcus parasanguinis, Staphylococcus saprophyticus, Veillonella parvula , Streptococcus australis, Haemophilus parainfluenzae, Staphylococcus warneri, Rothia aeria, Streptococcus thermophilus, Acinetobacter ursingii, Propionibacterium phage _P14_4, Veillonella dispar, Streptococcus infantis, Streptococcus cristatus, Staphylococcus pettenkoferi, Actinomyces odontolyticus and their mixtures, preferentially S. pasteuri , S. saprophyticus , S. warneri, S. pettenkoferi and mixtures thereof, more preferably S. pasteuri, S. warneri and mixtures thereof , and very preferably it is S. warneri.

In one embodiment of the invention, the use of N-methylglycine is to increase the diversity of the cutaneous microbial flora to decrease and/or prevent the loss of skin appendages, preferentially hair.

Advantageously, the term "reducing hair loss" means reducing by at least 0.5%, preferably by at least 1%, even more preferably by at least 2% the density of hair in the telogen phase, i.e. i.e. in the fall phase. The measurement of the density of the 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 N-methylglycine or of a composition comprising it, in particular a formulation in the form of a shampoo, in comparison with the density of hair in the telogen and anagen phase measured without N-methylglycine or without a composition comprising it.

In another embodiment, the use of N-methylglycine is to increase the diversity of the microbial flora of the skin, advantageously of the scalp, to prevent the appearance and/or reduce dandruff. Thus N-methylglycine is considered to be in an effective quantity to prevent the appearance and/or reduce dandruff when the concentration ratio of the strains of Staphylococcus (all species)/ P. acnes is at least half as large, advantageously at least 3 times lower after application of a formulation comprising N-methylglycine than said ratio measured after application of the same formulation not comprising N-methylglycine. Advantageously, this is a measurement of the ratio in concentration of strains of Staphylococcus (all species) / P. acnes after 28 days of application of a formulation for hair comprising 1% by weight of the preparation containing the N-methylglycine as prepared according to Example 1b), under the conditions described in Example 2.

Thus N-methylglycine is an ingredient inducing a feeling of exfoliation of the skin, especially the scalp.

N-methylglycine is obtained commercially in the form of a powder and can be dissolved in any solvent or mixture of solvents, preferably an aqueous solvent, and advantageously in water, an alcohol, a glycol, a polyol, a water/water mixture. alcohol, water/glycol or water/polyol (such as water mixed with ethanol, glycerol and/or butylene glycol and/or other glycols such as xylitol and/or propanediol, etc.) from 99/1 to 1/99 (w / w), advantageously in water as sole solvent.

In particular, the N-methylglycine solution is an aqueous solution. The term "aqueous solution of N-methylglycine" means any aqueous solution containing more than 60% by weight, advantageously at least 70% by weight, in particular at least 80% by weight, more particularly at least 90% by weight, so particular at least 95% by weight of water relative to the total weight of the aqueous solution, even more advantageously not containing any glycol and in particular not containing any alcohol, more particularly containing only water.

When it is used alone in the form of a cosmetic ingredient, N-methylglycine is advantageously dissolved in an aqueous solvent comprising glycerin, advantageously present at a concentration of 60% to 90%, again advantageously of 70% to 85%, very advantageously at a concentration of 82% by weight relative to the total weight of the aqueous solution.

Alternatively, the N-methylglycine is dissolved and/or diluted in a particularly polar solvent, such as water, an alcohol, a polyol, a glycol, such as pentylene glycol and/or butylene glycol and/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, caprylyl glycol and mixtures thereof, or glycerol. Advantageously, N-methylglycine is diluted and/or soluble in an aqueous solution containing hexylene glycol, in particular containing between 0.1 and 10% by weight of hexylene glycol, preferentially between 0.5 and 5% by weight of hexylene glycol, relative to the total weight of the cosmetic ingredient. Advantageously, the N-methylglycine is diluted and/or soluble in an aqueous solution containing caprylyl glycol, in particular containing between 0.01 and 5% by weight of caprylyl glycol, preferentially between 0.1 and 1% by weight of caprylyl glycol , relative to the total weight of the aqueous solution.

In a first embodiment of the invention, the N-methylglycine in powder form is dissolved in water as sole solvent, at a final concentration by weight of 7% relative to the total weight of the solution, as described in Example 1a).

In a second embodiment, the N-methylglycine in powder form is dissolved in an aqueous solution of glycerin (82% w/w), at a concentration by weight relative to the total weight of the final solution of 7%. The solution is then filtered (0.45 µm), as described in Example 1b).

Another object of the invention relates to the use of N-methylglycine in a cosmetic composition comprising at least one cosmetically acceptable excipient, to increase the diversity of the cutaneous microbial flora, advantageously of the scalp, to reduce and/or prevent hair loss. skin appendages, preferably hair, and/or to prevent the appearance and/or reduce dandruff.

"Acceptable" means a cosmetic excipient that is non-irritating to the skin, does not induce an allergic response, and is chemically stable.

In one embodiment of the invention, the N-methylglycine is present in the cosmetic composition at a final concentration of 1x10 ^-6 M to 1x10 ^-1 M, preferably from 1x10 ^-5 M to 1x10 ^-2 M, very preferably at a concentration of 7x10 ^{- 3} M.

Alternatively, N-methylglycine is present in the cosmetic composition comprising at least one cosmetically acceptable excipient at a final concentration by weight of 1% relative to the total weight of the composition.

The excipient(s) may be chosen from surfactants and/or emulsifiers, preservatives, buffering agents, chelating agents, denaturants, opacifying agents, pH adjusters, reducing agents, stabilizing agents, thickeners, gelling agents, film-forming polymers, fillers, matting agents, shine agents, pigments, colorants, perfumes, and mixtures thereof. The CTFA (Cosmetic Ingredient Handbook, Second Edition (1992)) describes various cosmetic excipients suitable for use in the present invention.

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

The cosmetic composition according to the invention can be chosen from an aqueous or oily solution, a cream or an aqueous gel or an oily gel, in particular a shower gel, a shampoo and a conditioner, a milk, an emulsion, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone-based, a mask, a serum, a lotion, a liquid soap, a dermatological bar, an ointment, a mousse, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of make-up powders, rods or sticks. Advantageously, it is a cream or a serum.

The cosmetic composition may also comprise other cosmetic active ingredients. Many cosmetically active ingredients are known to those skilled in the art to improve the health and/or physical appearance of the skin. On the other hand, the compounds described in the present invention can have a synergistic effect when combined with each other. 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. Examples of these classes of ingredients include, but are not limited to, the following compounds: abrasive, absorbents, compounds for aesthetic purposes such as perfumes, pigments, colorants, essential oils, astringents, e.g. clove, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, distillate of hamelis, anti-acne agents, anti-flocculent agents, anti-foam agents, anti-microbial agents (for example: iodopropyl butylcarbamate ), antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, additives, biocidal agents, denaturants, thickeners, and vitamins, and derivatives or equivalents thereof , film-forming materials, polymers, opacifying agents, pH adjusters, reducing agents, depigmenting or lightening agents (for example: hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), conditioning (for example: humectants).

The cosmetic composition may also comprise other cosmetic agents having the same properties and inducing a synergistic effect or not with the extract according to the invention, or cosmetic agents with complementary effects.

By way of anti-hair loss active ingredient, mention will be made of the combination of sulfopeptides, amino acids, aminosaccharides, vitamin B group, zinc and extract of Panax ginseng and Artium majus marketed under the name Trichogen™ LS 8960 by the applicant or an agent hair protector such as an extract of Litchi chinensis pericarp marketed under the name Litchiderm™ by the applicant, a soothing and anti-itching active ingredient such as rapeseed phytosterols marketed under the name Phytosoothe™ LS9766 by the applicant. Mention may also be made of the association with protective active ingredients for the scalp such as Purisoft™ or Puricare™.

As active agents for reducing the sensitivity of the scalp, mention will be made of active agents such as Elestab™ HP 100; PatcH ₂ O™, Sanicapyl™.

Finally, N-methylglycine can be combined with active ingredients that regulate sebum production in the skin and scalp, such as Asebiol™; Betapur™; Sebaryl™.

Other types of active ingredients may be present in the composition, such as an extract of Cassia alata leaves marketed under the name DN-Age™ as an antioxidant active ingredient for hair care in particular, a combination of an extract of Salvia miltiorhizza and niacinamide marketed under the name CollRepair™ as a deglycating agent, or active ingredients promoting skin firmness such as a synthetic tetrapeptide marketed under the name Dermican™ , an extract of Hibiscus abelmoschus marketed under the name Linefactor™, a purified pea extract marketed under the name Proteasyl™, an extract of Manilkara multinervis marketed under the name Elestan™, an extract of Khaya senegalensis marketed under the name Collalift™18, an extract of Argan pulp marketed under the name Argassential™ by the plaintiff, an extract of Schizandra chinensis marketed under the name Sqisandryl™, an extract of Eperua falcata marketed under the name Eperuline™, an extract of Orthosiphon staminus marketed under the name MAT-XS™ Bright marketed by the applicant. These combinations of active ingredients are likely to strengthen the hair follicle and reduce hair loss.

In an advantageous embodiment, the cosmetic composition is applied to all or part of the scalp and/or of the skin appendages, advantageously of the scalp.

Another object also relates to a cosmetic care process comprising the topical or oral administration, advantageously the topical application, of N-methylglycine or of a composition comprising it, in order to increase the diversity of the cutaneous microbial flora , advantageously of the scalp. In one embodiment, the method comprises the topical application of N-methylglycine or a composition comprising it on all or part of the scalp and / or skin appendages, advantageously the scalp.

Thus, advantageously, the cosmetic care process according to the invention is, in order to reduce and/or prevent the loss of skin appendages, preferably hair and/or to prevent the appearance and/or reduce dandruff, in particular by topical application N-methylglycine or a composition comprising it.

The invention also relates to a cosmetic treatment method for reducing and/or preventing the loss of skin appendages, preferably hair, and/or for preventing the appearance and/or reducing dandruff, of an individual who needs it. and/or who wishes, comprising the steps:
- the identification on the individual of an area of skin and/or cutaneous appendages which one wishes to reduce and/or prevent the loss of cutaneous appendages, preferably hair and/or whose appearance one wishes to prevent and/ or reduce dandruff
- the topical application to this area of skin and/or skin appendix of a cosmetic composition comprising N-methylglycine in an amount effective to reduce and/or prevent the loss of skin appendages, preferably hair, and/or to prevent the appearance and / or reduce dandruff

A final object of the invention relates to N-methylglycine or a pharmaceutical composition, advantageously dermatological, comprising it for its use to reduce itching and/or skin irritation, advantageously scalp irritation, and/or to prevent and/or reduce skin sensitivity, advantageously of the scalp. Here, "skin sensitivity" means sensations of skin tightness and/or pain to the touch and/or skin burning sensations, distinct from itching and irritation, also caused by an imbalance of the skin's microbial flora.

The term "reducing the itching and/or irritation" means reducing the adhesion of S. aureus to the skin, in particular the scalp. Thus, N-methylglycine is considered to be in an effective amount to reduce itching and / or skin irritation when the adhesion of S. aureus to the surface of the skin is reduced by at least 30%, advantageously by at least 44%, again advantageously at least 60% in the presence of N-methylglycine, in comparison with the percentage of adhesion measured without N-methylglycine. Advantageously again, it is a reduction in the adhesion of S. aureus to the surface of the scalp.

In an advantageous embodiment of the invention, the measurement of the percentage of adhesion of S. aureus is carried out in the presence of two distinct concentrations of N-methylglycine, at the level of human keratinocytes, under the conditions described in example 3 .

In one embodiment of the invention, the pharmaceutical composition, advantageously dermatological, comprises at least one dermatologically acceptable excipient. Advantageously, N-methylglycine is included in said composition at a concentration of 1x10^-6M at 1x10^-1M, preferably 1x10^-5M at 1x10^-2M, very preferably at a concentration of 7x10^{- 3} M. Alternatively, N-methylglycine is present in the pharmaceutical composition, advantageously dermatological, at a final concentration by weight of 1% relative to the total weight of the composition.

Examples referring to the description are shown below. These examples are given by way of illustration and in no way limit the scope of the invention. Each example is general in scope. The examples form an integral part of the present invention and any feature appearing new with respect to any state of the prior art from the description taken as a whole, including the examples, forms an integral part of the invention.

Unless otherwise specified, temperature is expressed in degrees Celsius (°C), the abbreviation "p" stands for weight and the abbreviation "v" stands for volume.

Examples

Example 1: Preparation of a solution of N-methylglycine

Ex. 1a): Commercial N-methylglycine powder (Sigma-Aldrich) was solubilized in water as sole solvent at a concentration by weight relative to the total weight of the final solution of 7%. The solution was filtered (0.45 µm).

Ex. 1b): Commercial powder of N-methylglycine (Sigma-Aldrich) was dissolved in an aqueous solution of glycerine (82% w/w), at a concentration by weight relative to the total weight of the final solution of 7%. The solution was filtered (0.45µm).
Example 2: Increase in Scalp Microbial Diversity in the Presence of N-Methylglycine

Protocol:

A clinical test was conducted on a population of 29 subjects (men and women) aged 23 to 66 with an oily scalp. A composition comprising 1% by weight of the preparation of N-methylglycine as prepared according to example 1b) relative to the total weight of the composition, was applied in the form of a mask to the entire scalp followed by a neutral shampoo three times a week for four weeks on a group of 17 volunteers; another group of 12 volunteers applied the composition not containing the product of the invention (control).

The quantity of sebum was evaluated on the scalp after two and four weeks of application.

The microbial flora of the scalp was sampled at the start of the study (T0) and at the end of the study (after 4 weeks of application of the formulation comprising N-methylglycine T28) using the technique swab (cotton swab). The microbial DNAs were extracted after enzymatic lysis, purified on a silicone membrane and quantified by fluorescence. All the DNAs contained in the samples were analyzed by complete metasequencing of the entire genome. The results are presented in Table 1 for the overall increase in microbial diversity, and in Table 2 for the qualitative analysis of the strains detected.

Results :

2a) Increased microbial diversity of the scalp

Sample AVERAGE T0 control 2.33 T28 control 2.16 N-methylglycine according to Example 1b (1% w/w) T0 1.84 N-methylglycine according to Example 1b (1% w/w) T28 2.24 * /T0

(*) p<0.1 versus T0

Conclusion: the microbial diversity of the scalp increased by 21.7% in 28 days in the presence of N-methylglycine.

2a)bis Qualitative analysis of the microbial diversity of the scalp

A negative value means that the strain is statistically representative of the microbial population at the start of the study (T0). A positive value means that the strain is statistically representative of the microbial population at the end of the study (T28).

It is therefore a question of measuring the evolution of the relative content of bacteria in the presence of the formulation tested (control formulation or formulation containing N-Methylglycine) (i.e. rationalized on the total population studied ).

Species identified Formulation control N-methylglycine formulation Significance of the difference before after Malassezia globosa -0.149 -* p = 0.048 (*) g-Dermatophilaceae- unclassified -0.135 - p = 0.014 (*) Dolosigranulum pigrum 0.163 - p=0.029 (*) Unclassified Escherichia 0 , 287 - p = 0.002 (**) Unclassified Dermabacteraceae - -0.149 p = 0.009 (**) Unclassified Brevicaterium - -0.15 p = 0.011 (*) g-Dermatophilaceae- unclassified - -0.093 p = 0.022 (*) Streptococcus salivarus - 0.312 p = 0.001 (***) Staphylococcus pasteuri - 0.215 p = 0.002 (**) Rhotia mucilaginosa - 0.213 p = 0.001 (***) Streptococcus parasanguinis - 0.199 p = 0.015 (*) Staphylococcus saprophyticus - 0.199 p = 0.009 (**) Unclassified Granulicatella - 0.168 p = 0.02 (*) Unclassified Veillonella - 0.162 p = 0.019 (*) Veillonella parvula - 0.137 p=0.018 (*) Streptococcus australis - 0.129 p = 0.018 (*) Haemophilus parainfluenzae - 0.153 p = 0.020 (*) Staphylococcus warneri - 0.141 p = 0.032 (*) Rothia aeria - 0.135 p = 0.025 (*) Streptococcus thermophilus - 0.123 p = 0.032 (*) Acinetobacter ursingii - 0.161 p = 0.032 (*) Propionibacterium phage _P14_4 - 0.124 p = 0.036 (*) Veillonella dispar - 0.131 p = 0.043 (*) Streptococcus infantis - 0.123 p = 0.045 (*) Streptococcus cristatus - 0.105 p = 0.043 (*) Staphylococcus pettenkoferi - 0.103 p = 0.041 (*) Unclassified Facklamia - 0.081 p = 0.037 (*) Actinomyces odontolyticus - 0.074 p = 0.047 (*) g- Unclassified Propionibacteriaceae - 0.074 p = 0.033 (*)

(-) means not representative and not applicable in this group / formulation.

(*) p<0.05; (**) p<0.01; (***) p<0.001

2b) Reduction and stabilization of the overall quantity of Staphylococcus strains.

AVERAGE T0 control 0.211 T28 control 0.83**/T0 N-methylglycine solution according to Example 1b (1% w/w) T0 0.262 N-methylglycine solution according to Example 1b (1% w/w) T28 0.23***/Control

**p=0.005 versus T0; *** p = 0.001 versus control.

Conclusion: the overall population of Staphylococcus strains (all species) decreased significantly less after 28 days of application of a shampoo comprising N-methylglycine compared to the application of a shampoo not comprising it. . N-methylglycine therefore makes it possible to stabilize the population of Staphylococcus strains.

2c) Reduction and stabilization of the Staphylococcus / P. acnes ratio and effect on the reduction of dandruff.

MEDIAN T0 control 0.319 T28 control 1.641°/T0 N-Methylglycine (1% w/w) T0 0.165 N-Methylglycine (1% w/w) T28 0.417*

(°) p<0.1 versus T0; (*) p=0.037< 0.05 versus control

Conclusion: The appearance of dandruff has been shown to be correlated with an increase in the Staphylococcus population, and in particular with an increase in the Staphylococcus / P. acnes ratio. However, the presence of N-methylglycine at a final concentration of 0.07% (w / w) in the cosmetic formulation slowed down the increase in the ratio of the amount of Staphylococcus (all species) compared to the amount of P. acnes , showing the ability of N-methylglycine to reduce dandruff.
Example 3: Decreased adherence of S. aureus and decreased itching and skin irritation.

Protocol: N-methylglycine solutions at final concentration by weight relative to the final volume of solutions of 3x10 ^-2 and 6x10 ^-2 % (w / v) were contaminated with S. aureus previously labeled with CFSE (Carboxyfluorescein succinimidyl ester) , at 1.108 to 1.109 CFU/mL. At the end of the contamination, the solutions were homogenized and each mixture was incubated for a period of 1 hour at a temperature of 37° C. and brought into contact with a carpet of keratinocytes. The whole was incubated for 1 hour at a temperature of 37°C. The cells were rinsed then the fluorescence was measured at excitation (max)=492 nm, emission (max)=517 nm.

Results :

AVERAGE Control 100 N-methylglycine (3 x 10 ^-2 % w/v) 35.57 N-methylglycine (6 x 10 ^-2 % w/v) 55.88

Conclusion : N-methylglycine reduced the adhesion of S. aureus to keratinocytes, showing its effectiveness in reducing itching and irritation of the scalp.
Example 4: example of cosmetic ingredient comprising N-methylglycine

The percentages are expressed by weight relative to the final volume of the ingredient.

Glycerin 82% N-methylglycine 7% Water 11% Example 5: Example of cosmetic formulation as a mask:

Name % (w/v) Distearoyl Hydroxy ethylmonium methosulfate and cetearyl alcohol 2.00 Sucrose polystearate and hydrogenated polyisobutene 2.00 Cetearyl alcohol 4.00 Dicaprylyl carbonate 2.00 Butyrospermum parkii butter 0.50 Phenoxyethanol and ethylhexylglycerin 1.00 Water 84.50 Polyquaternium-37, Dicaprylyl Carbonate, Lauryl Glucoside 1.00 Cetrimonium Chloride 2.00 N-Methylglycine 7% (w/v) 1.00

Claims (12)

Use of N-methylglycine as a skin prebiotic. Non-therapeutic cosmetic use of N-methylglycine according to Claim 1 for increasing the diversity of the cutaneous microbial flora, advantageously of the scalp. Use according to any one of claims 1 or 2 for reducing and/or preventing the loss of skin appendages, preferably hair, and/or for preventing the appearance and/or reducing dandruff. Use according to any one of Claims 1 to 3, characterized in that it is a topical use. Use according to any one of Claims 1 to 4, characterized in that the N-methylglycine is included in a cosmetic composition comprising at least one cosmetically acceptable excipient, the said N-methylglycine being present at a final concentration of 1x10 ^-6 M at 1x10 ^-1 M, preferably from 1x10 ^-5 M to 1x10 ^-2 M, very preferably at a concentration of 7x10 ^{- 3} M. Use according to any one of Claims 1 to 4, characterized in that the N-methylglycine is present in a cosmetic composition, comprising at least one cosmetically acceptable excipient, at a final concentration by weight of 1% relative to the total weight of the composition. Use according to any one of Claims 5 or 6, characterized in that the composition is applied to all or part of the scalp and/or of the skin appendages, advantageously of the scalp. Use according to any one of claims 1 to 7 to promote the appearance of beneficial commensal strains chosen from Streptococcus salivarus, Staphylococcus pasteuri, Rhotia mucilaginosa, Streptococcus parasanguinis, Staphylococcus saprophyticus, Veillonella parvula, Streptococcus australis, Haemophilus parainfluenzae, Staphylococcus warneri, Rothia aeria, Streptococcus thermophilus, Acinetobacter ursingii, Propionibacterium phage _P14_4, Veillonella dispar, Streptococcus infantis, Streptococcus cristatus, Staphylococcus pettenkoferi, Actinomyces odontolyticus and mixtures thereof, preferably chosen from S. pasteuri, S. saprophyticus, S. warneri, S. pettenkoferi and their mixtures , again preferably chosen from S. pasteuri, S. warneri and mixtures thereof, and very preferably it is S. warneri. Cosmetic care process comprising the topical or oral administration, advantageously the topical application, of N-methylglycine or of a composition comprising it, in order to increase the diversity of the cutaneous microbial flora, advantageously of the scalp. Cosmetic care process according to claim 9 for reducing and/or preventing the loss of skin appendages, preferably hair, and/or for preventing the appearance and/or reducing dandruff. N-methylglycine or pharmaceutical composition, advantageously dermatological, comprising it for its use to reduce itching and/or skin irritation, advantageously scalp irritation, and/or to prevent and/or reduce skin sensitivity, advantageously of the scalp . N-methylglycine for its use according to Claim 11, characterized in that it is present in the pharmaceutical composition at a concentration of 1x10 ^-6 M to 1x10 ^-1 M, preferentially from 1x10 ^-5 M to 1x10 ^-2 M, very preferentially at a concentration of 7x10 ^-3 M.