Composition for the treatment of vitiligo

Abstract

The invention relates to a composition which aims to prevent and / or treat, in a subject, the early stage of vitiligo corresponding to the deregulation of the mitochondrial function of keratinocytes and melanocytes associated with an abnormally high level of ROS within these mitochondria, which composition comprises at least one strain of Bifidobacterium longum or Bifidobacterium breve, or a lysate thereof.

Description

Title of the invention: Composition for the treatment of vitiligo Field of invention

[0001] The present invention relates to compositions and their use in the treatment or prevention of vitiligo. State of the art

[0002] Vitiligo is a skin condition characterized by the appearance of white spots on the hands, feet, face, or any other part of the body. These spots are caused by depigmentation, which corresponds to the disappearance of melanocytes. This depigmentation can be more or less significant and the white spots can vary in size. In some cases, the hair or hair growing within the depigmented areas may also be white.

[0003] Vitiligo is neither contagious nor painful, but it can cause significant psychological distress. It should be noted that people with dark skin suffer from it in particular, as the condition is even more visible in them. However, the impact on quality of life is significant for all those affected. Vitiligo is still insufficiently treated by doctors.

[0004] Vitiligo affects approximately 0.5 to 2% of the world's population, regardless of ethnic origin or gender. It usually appears around the age of 10 to 30, with half of those affected developing it before the age of 20. Vitiligo is therefore quite rare in young children. It affects both men and women.

[0005] There are several types of vitiligo:

[0006] 1) Segmental vitiligo, located on one side of the body, for example on a part of the face, upper body, leg, or arm. This form of vitiligo occurs more often in children or adolescents. This form appears rapidly within a few months and then usually stops progressing.

[0007] 2) Non-segmental vitiligo which appears in the form of spots often more or less symmetrical, affecting both sides of the body. The progression is unpredictable, with spots remaining small and localized or spreading rapidly.

[0008] Most often, the disease progresses at an unpredictable pace and can stop or spread continuously or most often in flare-ups. Vitiligo can thus progress in phases, with worsenings sometimes occurring after a psychological or physical triggering event. In very rare cases, the plaques disappear on their own. These people are also more likely to suffer from other autoimmune diseases, including autoimmune thyroid disorders.

[0009] Vitiligo is a multifactorial polygenetic disease leading to the loss of melanocytes.

[0010] Several hypotheses are currently being put forward to explain the loss of melanocytes. Vitiligo is probably a pathology that has genetic, environmental and autoimmune origins. Vitiligo is a disease with a strong autoimmune component. The involvement of cellular immunity and in particular the IFN gamma pathway is now well demonstrated. Innate immunity is also involved and provides the link between external or internal stress factors and the activation of adaptive immunity.

[0011] According to several studies, the keratinocytes and melanocytes of people with vitiligo would first accumulate numerous free radicals, which would then lead to the production of cytokines and chemokines by the keratinocytes and melanocytes and the activation of the immune system.

[0012] To date, vitiligo treatments often require many months and are mainly effective for facial lesions. Failures remain numerous, particularly for bony protrusions and the hands and feet. The standard treatment combines phototherapy (at best UV-B) with local treatments using dermocorticoids or calcineurin inhibitors. Very active forms can benefit from mini-pulses of cortisone. Finally, localized and stable forms and segmental vitiligo are good indications for surgical treatment, particularly by epidermal cell suspension grafting.

[0013] There is therefore a strong demand for a more effective, well-tolerated and more affordable therapy. The topical route is an alternative, but only small molecules are suitable for passing into the epidermis and targeting keratinocytes and melanocytes effectively. Description of the embodiments

[0014] The inventors have now demonstrated that extracts of bacterial strains belonging to the species Bifidobacterium longum or Bifidobacterium breve exhibited a particularly significant activity in reducing mitochondrial oxidative stress in a cellular model associated with the early stage of vitiligo corresponding to the deregulation of the mitochondrial function of keratinocytes.

[0015] Consequently, a first aspect of the invention relates to a composition which aims to prevent and / or treat, in a subject, the early stage of vitiligo corresponding to the deregulation of the mitochondrial function of keratinocytes and melanocytes associated with an abnormally high level of ROS within these mitochondria, which composition comprises at least one strain of Bifidobacterium longum or Bifidobacterium breve, or a lysate thereof.

[0016] Preferably, said composition aims to prevent and / or treat a subject suffering from vitiligo.

[0017] In relation to vitiligo, this can correspond equally well to segmental vitiligo or non-segmental vitiligo.

[0018] As for the subject, it is a mammal and, preferably, a human.

[0019] Bifidobacterium is a genus of Gram-positive, anaerobic, bifidobacterial actinobacteria. These bacteria consist of irregularly shaped, strictly anaerobic, catalase-negative, immobile bacilli. Bifidobacteria belong to the family of lactic acid bacteria. They participate in the fermentation of milk in the manufacture of cheese and yogurt-like preparations. In addition, they produce large quantities of lactic acid, which lowers the pH, which is favorable to them and would inhibit the growth of other germs. The species Bifidobacterium longum or Bifidobacterium breve are present in the human digestive tract.

[0020] Advantageously, the content of the composition according to the invention in at least one strain of Bifidobacterium longum or Bifidobacterium breve is between 102 and 1013 CFU / ml of composition, preferably it is between 105 and 1011 CFU / ml of composition.

[0021] By lysate is meant a culture of such a bacterial strain which has been subjected to cell lysis.

[0022] Cell lysis can be achieved by multiple technologies such as osmotic shock, thermal shock, ultrasound treatment or mechanical stress (e.g. centrifugation).

[0023] Advantageously, such a lysate is obtained by lysis by thermal shock or by ultrasound.

[0024] Typically, such a lysate may be obtained according to the technology described in US patent No. 4,464,362 and in particular by following the protocol below.

[0025] Microorganisms corresponding to Bifidobacterium species are cultivated under anaerobic conditions in a suitable culture medium (see for example US patents No. 4,464,362 and EP 0 043 128 B1). When the stationary development phase is reached, the cultures are inactivated by pasteurization, for example by a temperature of 60 to 65 °C for 30 minutes. The microorganisms are then collected by a conventional separation technique, for example by membrane filtration, centrifugation and resuspension in sterile physiological saline solution. The lysate is then obtained by ultrasonic disintegration of the microorganisms so as to release the cytoplasmic fractions, the cell wall fragments and the products of metabolism. All these components are then stabilized in a weakly acidic solution.

[0026] Preferably, it is a lysate of Bifidobacterium longum (CAS No. 96507-89-0). As an example of such a lysate, mention may be made of the product registered under the deno- “REPAIR COMPLEX CLR™” program by K. RICHTER GmbH.

[0027] Advantageously, the content of the composition according to the invention in lysate of at least one strain of Bifidobacterium is between 1 and 20% (by weight relative to the total weight of the composition), preferably it is between 5 and 10%.

[0028] By Antioxidant, we mean a molecule capable of blocking or slowing down the oxidation of another molecule upon contact with it.

[0029] This class of molecules includes a large number of components, including vitamins, metallic species, peptides or peptide derivatives, polyphenols, flavonols and organosulfur compounds.

[0030] As vitamins exhibiting antioxidant activity, mention may be made of vitamin A, vitamin C, vitamin E, coenzyme Q10 and their derivatives.

[0031] As metallic species exhibiting antioxidant activity, mention may be made of selenium and zinc.

[0032] As pigments exhibiting antioxidant activity, mention may be made of [3-carotene, lycopene or curcumin.

[0033] As peptides or peptide derivatives exhibiting antioxidant activity, mention may be made of L-carnosine, Glutathione or Superoxide dismutase (SOD). L-carnosine is a dipeptide of beta-alanine and histidine available in particular under the name SPECPED®LCS (SPEC-CHEM IND) or DRAGOSINE® (SIMRISE). Glutathione is a pseudo-tripeptide formed by the condensation of glutamic acid, cysteine ​​and glycine which is available in particular under the name SPECKAREE® GSH (SPEC-CHEM IND) or AC-GSH (SOHO ANECO CHEMICALS). Superoxide dismutase (SOD) are metalloproteins catalyzing the dismutation of superoxide anions into oxygen and hydrogen peroxide. SODs are available in particular under the name BIOCELL SOD (LONZA) or DISMUTIN®PF (DSM).

[0034] As polyphenols exhibiting antioxidant activity, we can cite anthocyanins in red fruits, proanthocyanidins in chocolate, ca-feroylquinic and feruloylquinic acids in coffee, flavonoids in citrus fruits, catechins in green tea, or quercetin in apples.

[0035] As flavonols exhibiting antioxidant activity, mention may be made of quercetol or PYCNOGENOL®.

[0036] As organosulfur compounds exhibiting antioxidant activity, mention may be made of lipoic acid, methionine or even cysteine.

[0037] Advantageously, the antioxidant content of the composition according to the invention is between 0.05 and 10% (by weight relative to the total weight of the composition). Indeed, the antioxidant content to be adopted is likely to vary greatly depending on the antioxidant capacity of the chosen molecule.

[0038] Now, the inventors have demonstrated that sinapine and its derivatives also exhibit a particularly significant activity in reducing mitochondrial oxidative stress in the same cellular model. Therefore, a combination of this antioxidant and the bacterial species (or their lysates) mentioned above is of definite interest for the treatment of this early stage of vitiligo.

[0039] According to a preferred embodiment, the antioxidant is sinapine, a salt thereof, or one of their derivatives.

[0040] Sinapine is an alkaloid having the formula (I)

[0041] O , (I) ,...0.. JL ■ x :J . O - . HO" Y .....o

[0042] By sinapine derivative is meant a compound having the formula (II)

[0043] O (II)

[0044] In which

[0045] - Ri and R3 are independently chosen from a hydrogen atom or a C1-C8 alkyl group, preferably a C1-C4 alkyl group and, particularly preferably, a C1-C2 alkyl group; and

[0046] - R2 is independently chosen from a hydrogen atom or a group C1 to C8 alkyl, preferably a C1 to C4 alkyl group and, particularly preferably, a C1 to C2 alkyl group.

[0047] Sinapine is present in quantity in the seeds or germs of plants of the Brassicaceae family, such as rapeseed (Brassica napus), watercress (Lepidum sativum), mustard (Brassica alba).

[0048] Advantageously, the sinapine is in the form of an extract of a seed or a germ of a plant belonging to the Brassicaceae family.

[0049] The term "extract" refers to a substance extracted from a natural product, regardless of its extraction method or the composition of the ingredients. For example, this includes those obtained by extracting soluble ingredients from a natural product using water or an organic solvent, or those obtained by extracting only specific ingredients, such as oil, from a natural product. Extraction methods are well known to those skilled in the art and consist of typically by macerating the seeds, crushed or not, in the extraction solvent.

[0050] Preferably, the extract of seeds or germs of a plant belonging to the Brassicaceae family is an aqueous, alcoholic or hydro-alcoholic extract. Advantageously, an extract using glycerin as an extraction solvent will be used, such as glycerin, hydroglycerin or glycerin hydroalcoholic extracts.

[0051] As an example of such extracts, mention may be made of an aqueous extract of mustard sprouts such as that marketed by the company MIBELLE under the name LIPERFECTION or the hydroglycerinated extract of watercress sprouts marketed by the company MIBELLE under the name DETOXOPHANE.

[0052] According to a preferred embodiment, the composition according to the invention is intended for topical application to the skin, in particular the skin of the face, hands, neck and body in general. As such, the composition according to the invention takes the form of a cream, a serum, a milk, a lotion or a gel. Preferably, the composition according to the invention will take the form of a cream.

[0053] The composition according to the invention is then applied to the affected skin surface at least once a day, preferably at least twice a day (e.g.: once in the morning and once in the evening).

[0054] Generally, the topical composition according to the invention may comprise numerous types of adjuvants or active ingredients used in pharmaceutical or cosmetic formulations, preferably dermatological formulations, whether fatty substances, organic solvents, thickeners, gelling agents, softeners, opacifiers, stabilizers, foaming and / or detergent surfactants, emollients, superfatting agents, perfumes, ionic or non-ionic emulsifiers, fillers, sequestering agents, chelators, preservatives, essential oils, coloring materials, pigments, hydrophilic or lipophilic active ingredients, humectants, such as for example glycerin or glycols, preservatives, colorants, cosmetic active ingredients, mineral and / or organic sunscreens, mineral fillers, synthetic fillers, elastomers. silicones, or plant extracts or even lipid vesicles,or any other ingredient usually used in cosmetics.

[0055] Now and advantageously, the composition according to the invention will not comprise paraben.

[0056] Still advantageously, the composition according to the invention will not comprise phenoxyethanol.

[0057] Examples of oils include paraffins, isoparaffins, white mineral oils, vegetable oils (from flowers, fruits, vegetables, trees, cereals, oilseeds, etc.), animal oils, synthetic oils, silicone oils and fluorinated oils; and more particularly: oils of vegetable, such as sweet almond oil, coconut oil, castor oil, jojoba oil, olive oil, rapeseed oil, peanut oil, sunflower oil, wheat germ oil, corn germ oil, soybean oil, cottonseed oil, alfalfa oil, poppy seed oil, pumpkin oil, evening primrose oil, millet oil, barley oil, rye oil, safflower oil, candlenut oil, passionflower oil, hazelnut oil, palm oil, shea butter, apricot kernel oil, calophyllum oil, sisymbra officinalis oil, avocado oil, calendula oil, oils derived from flowers or vegetables; ethoxylated vegetable oils; oils of animal origin, such as squalene, squalane; mineral oils, such as paraffin oil, vaseline oil and isoparaffins;synthetic oils, including fatty acid esters such as butyl myristate, propyl myristate, cetyl myristate, isopropyl palmitate, butyl stearate, hexadecyl stearate, isopropyl stearate, octyl stearate, isocetyl stearate, dodecyl oleate, hexyl laurate, propylene glycol dicaprylate;esters derived from lanolic acid, such as isopropyl lanolate, isocetyl lanolate, monoglycerides, diglycerides and triglycerides of fatty acids such as glycerol triheptanoate, alkylbenzoates, polyalphaolefins, polyolefins such as polyisobutene, synthetic isoalkanes such as isohexadecane, isododecane, perfluorinated oils and silicone oils. Among the latter, we can more particularly cite dimethylpolysiloxanes, methylphenylpolysiloxanes, silicones modified by amines, silicones modified by fatty acids, silicones modified by alcohols, silicones modified by alcohols and fatty acids, silicones modified by polyether groups, modified epoxy silicones, silicones modified by fluorinated groups, cyclic silicones and silicones modified by alkyl groups.

[0058] As other fatty substances, mention may be made of linear or branched, saturated or unsaturated fatty alcohols, mixtures of linear and / or branched, saturated and / or unsaturated fatty alcohols, or linear or branched, saturated or unsaturated fatty acids, mixtures of linear or branched, saturated or unsaturated fatty acids.

[0059] Among the thickening and / or emulsifying polymers that can be used, there are, for example, homopolymers or copolymers of acrylic acid or acrylic acid derivatives, homopolymers or copolymers of methacrylic acid or methacrylic acid derivatives, homopolymers or copolymers of acrylamide, homopolymers or copolymers of acrylamide derivatives, homopolymers or copolymers of acrylamidomethyl propanesulfonic acid, homopolymers or copolymers of vinyl monomers, homopolymers or copolymers of trimethylaminoethylacrylate chloride, hydrocolloids of plant or biosynthetic origin such as, for example, xanthan gum, karaya gum, car- raghenates, alginates; silicates; cellulose and its derivatives; starch and its hydrophilic derivatives; polyurethanes.

[0060] Among the polyelectrolyte type polymers that can be used in the production of a gelled aqueous phase suitable for use in the preparation of W / O, O / W, W / O / W or O / W / O emulsions, or of an aqueous gel comprising SEPIBIO™ POTENTILLA 217, there are, for example, copolymers of acrylic acid and 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid (AMPS), copolymers of acrylamide and 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid, copolymers of 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid and (2-hydroxyethyl)acrylate, 2-methyl-[(l-oxo-2-propenyl)amino]-1-propanesulfonic acid homopolymer, acrylic acid homopolymer, copolymers of acryloyl ethyl trimethyl ammonium chloride and acrylamide, copolymers of AMPS and vinylpyrrolidone, copolymers of AMPS and N,N-dimethylacrylamide., terpolymers of AMPS, acrylic acid and N,N-dimethylacrylamide, copolymers of acrylic acid and alkyl acrylates whose carbon chain comprises between ten and thirty carbon atoms, copolymers of AMPS and alkyl acrylates whose carbon chain comprises between ten and thirty carbon atoms.

[0061] Among the waxes that can be used in the compositions according to the invention, mention may be made, for example, of beeswax, carnauba wax, Candelilla wax, Ouricoury wax, Japan wax, China wax, rice bran wax, Montan wax, cork or sugar cane fiber wax, paraffin waxes, lignite waxes, microcrystalline waxes, lanolin wax, ozokerite, polyethylene wax, hydrogenated oils, silicone waxes, alkenone waxes, vegetable waxes, fatty alcohols and fatty acids that are solid at room temperature, and glycerides that are solid at room temperature.

[0062] Among the emulsifiers that can be used in the compositions according to the invention, mention may be made of:

[0063] - fatty esters of alkylpolyglycosides, optionally alkoxylated;

[0064] - alkoxylated fatty esters;

[0065] - fatty chain polyalkylene glycol carbamates;

[0066] - fatty acids, ethoxylated fatty acids, fatty acid esters of sorbitol, ethoxylated fatty acid esters, polysorbates, polyglycerol esters, ethoxylated fatty alcohols, sucrose esters, alkylpolyglycosides, sulfated and phosphated fatty alcohols or mixtures of alkylpolyglycosides and fatty alcohols;

[0067] - associations of emulsifying surfactants chosen from alkylpoly glycosides;

[0068] - combinations of alkylpolyglycosides and fatty alcohols, polyglycerol esters or polyglycols or polyols.

[0069] Among the surfactants which can be used in the compositions according to the invention, mention may be made of: topically acceptable anionic, cationic, amphoteric or non-ionic surfactants usually used in this field of activity.

[0070] Among the anionic surfactants which can be used in the compositions according to the invention, mention will be made in particular of the alkali metal salts, the alkaline earth metal salts, the ammonium salts, the amino acid salts, the amino alcohol salts of the following compounds: alkyl ether sulfates, alkyl sulfates, alkylamidoether sulfates, alkylarylpolyether sulfates, monoglyceride sulfates, alpha-olefinsulfonates, paraffin sulfonates, alkylphosphates, alkyletherphosphates, alkylsulfonates, alkylamidesulfonates, alkylarylsulfonates, alkylcarboxylates, alkylsulfosuccinates, alkylethersulfosuccinates, alkylami-desulfosuccinates, alkylsulfoacetates, alkylsarcosinates, acylisethionates, N-acyltaurates, acyllactylates.

[0071] Among the amphoteric surfactants which can be used in the compositions according to the invention, mention may be made of alkylbetaines, alkylamidobetaines, sultaines, alkylamidoalkylsulfobetaines, imidazoline derivatives, phosphobetaines, amphopolyacetates and amphopropionates.

[0072] According to another preferred embodiment, the composition according to the invention is intended for oral administration which can take the form of a nutritional supplement or a dietary preparation.

[0073] For example, said nutritional supplement or said dietary preparation may be in the form of granules, tablets, soft capsules, gel caps, suspensions, syrups, ampoules, mouth sprays, drops, walking gums, dissolving powders or solutions.

[0074] In the case of a powder to be dissolved in a liquid, which liquid can then be for example water, milk or a milk-based preparation, or even fruit juice.

[0075] Other pharmaceutically and / or food-acceptable agents may be added, such as bulking agents, fluidizers, natural extracts, minerals, trace elements, fatty acids, anti-caking agents, natural oils, flavorings, colorings, acidifiers, thickeners, preservatives and sweeteners.

[0076] Examples of bulking agents include microcrystalline cellulose, potato maltodextrin or magnesium lactate.

[0077] Examples of fluidizers include magnesium silicate, magnesium stearate or colloidal silica.

[0078] Examples of minerals or trace elements include magnesium, iodine, iron, copper, zinc, selenium, chromium, molybdenum, manganese, silicon, vanadium, nickel or even tin.

[0079] Examples of amino acids that may be mentioned include alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan or tyrosine.

[0080] Examples of fatty acids that may be mentioned are unsaturated fatty acids such as omega-3 or omega-6.

[0081] Examples of anti-caking agents commonly used in the food industry include magnesium stearate (E470b), silicon dioxide (E551) and colloidal silica.

[0082] Examples of thickeners that may be mentioned include potato starch, hydroxypropylmethylcellulose, citrus pectin, guar gum, carob gum, xanthan gum, agar-agar, konjac, hydrogenated oils or even beeswax.

[0083] As an example of acidifiers, citric acid may be mentioned.

[0084] Examples of sweeteners that may be mentioned include, among others, xylitol, aspartame, glucose syrup, fructooligosaccharide syrup, maltitol powder or syrup, acesulfame potassium, fructooligosaccharide, sodium cyclamate, sucralose.

[0085] As colorants, mention may be made of curcumins (E100), carminic acid (E120), erythrosine (E127), chlorophylls and chlorophyllins (E140), copper-chlorophyll and chlorophyllin complexes (E141), caramel (E150), carotenes (E160), anthocyanins (E163), calcium carbonate (E170), iron oxide and hydroxide (E172) or even orcein (E182).

[0086] Examples of preservatives include potassium sorbate, sodium benzoate or ascorbyl palmitate (antioxidant).

[0087] In order to further potentiate the activity obtained by the composition according to the invention, it may be combined with other active ingredients, in particular those known for their anti-aging, firming, restructuring, stimulating, energizing, anti-wrinkle, relaxing, moisturizing, antimicrobial, sebum-regulating, purifying, soothing, relaxing, decontracting, anti-stress, lightening, immunomodulating, cell renewal stimulating, lifting, plumping, complexion radiance improving action, etc.

[0088] According to a second object, the composition described above is used in a method which aims to prevent and / or treat vitiligo in a subject and comprises a step of administering a therapeutically effective amount of the latter on a skin surface of said subject.

[0089] By "therapeutically effective amount" is meant an amount sufficient to achieve the desired biological effect.

[0090] The invention will be better understood in light of the following examples, which are given purely for illustrative purposes and are not intended to limit the scope of the invention, defined by the appended claims. Examples

[0091] 1) Ability to induce a drastic decrease in ROS within the mitochondria of ke- ratinocytes of certain specific bacterial extracts

[0092] Primary human keratinocytes (PHK) were isolated from the foreskin of healthy children and cultured in serum-free medium supplemented with bovine pituitary extract (250 pg / mL) and EGF (0.25 ng / mL).

[0093] The NHKs are then seeded onto 6-well plates and incubated in a controlled atmosphere. When the keratinocytes have reached 70 to 80% confluence, the cells are pretreated or not for one hour with different components. As a positive control, the NHKs are pretreated for one hour with sinapine (100 pM).

[0094] The plates are then washed 3 times with a PBS solution before incubating the pretreated NHKs for one hour in the presence of H2O2 (100 pM) or LPS (100 ng / mL).

[0095] At the end of the incubation, the cells are incubated in a dihydro-rhodamine solution (5 pM) for 30 minutes at 37°C, which allows the labeling of ROS, in particular mitochondrial ROS.

[0096] After 3 washes with PBS solution, mitochondrial ROS are quantified by FACS.

[0097] The results are presented in Table 1 below.

[0098] [Tables 1] Pretreatment Treatment Mitochondrial ROS level (%) - basal 100 H2O2 352 LPS 124 Sinapine - 100 h2o2 100 LPS 97 B. longum extract - 32 h2o2 12.7 LPS 15.8 B. breve extract - 35 h2o2 7 LPS 5.2 Sinapine+longum... H2O2 2 Sinapine+breve h2o2 1

[0099] Completely unexpectedly, the results showed that extracts of Bifidobacterium longum and Bifidobacterium breve induced a drastic decrease in ROS within the mitochondria of keratinocytes subjected or not to stress, and even to major oxidative stress (H2O2). It should be noted that the observed decrease is specific to the bacterial species used. Indeed, this decrease is not observed with bacterial extracts of the species Bifidobacterium bifidum and Bifidobacterium lactis. The observed decrease in ROS within the mitochondria of keratinocytes with extracts of Bifidobacterium longum and Bifidobacterium breve is much greater than that observed with sinapine.

[0100] The results show that the combination of Bifidobacterium longum and Bifidobacterium breve extracts and sinapine makes it possible to obtain a composition with an even greater potential for reducing ROS within the mitochondria of keratinocytes.

[0101] The same tests are carried out on melanocytes.

[0102] 2) Ability to induce a drastic decrease in the expression of pro-cytokines inflammatory within keratinocytes by certain specific bacterial extracts

[0103] Primary human keratinocytes (NHK) were isolated from the foreskin of healthy children and cultured in serum-free medium supplemented with bovine pituitary extract (250 pg / mL) and EGF (0.25 ng / mL).

[0104] The NHKs are then seeded onto 6-well plates and incubated in a controlled atmosphere. When the keratinocytes have reached 70 to 80% confluence, the NHKs are incubated for one hour in the presence of LPS (100 ng / mL) or IFN / TNF (10 ng / ml) for 24 hours.

[0105] At the end of the incubation, the cells are incubated or not in the presence of 100 pg / mL of extracts of different strains of Bifidobacterium for 24 hours. At the end of this incubation period, the supernatants are collected for an ELIS A assay (TNF alpha, IFN gamma, IL1 beta, CXCL10, CXCL11, and CXCL16).

[0106] The results are shown in [Fig.l].

[0107] As previously, the results showed that extracts of Bifidobacterium longum and Bifidobacterium breve induced, as for mitochondrial ROS, a drastic decrease in the expression of different pro-inflammatory cytokines within keratinocytes subjected or not to stress. Here again, the observed decrease is specific to the bacterial species used. Indeed, this very significant decrease is not observed with bacterial extracts of the species Bifidobacterium bifidum and Bifidobacterium lactis.

[0108] Again, the same tests are carried out on melanocytes.

[0109] 3) composition according to the invention

[0110] Based on the previous results, a composition was developed comprising an extract of Bifidobacterium longum and a plant extract comprising sinapine so as to prevent the appearance of new lesions or to stabilize them in subjects at an early stage of vitiligo, namely having melanocytes whose mitochondrial function. The details of a composition according to the invention are given in Table 2 below. [YES] [Tables2] Compounds Presence in the composition (% by weight compared to the total weight) REPAIR COMPLEX CLR™ 5 to 10 LIPERFECTION 2 to 5 Glycerin 4 to 5 C12-C15 alkyl benzoate 1 to 4 Ethylhexyl palmitate 4 to 5 Glyceryl stearate 1 to 3 Cyclomethicone 5 to 8 Potassium cetyl phosphate 1 to 3 Hydroxyethyl acrylate 0.8 to 2.3 Xanthan gum 0.1 to 0.35 Magnesium silicate 0.3 α-tocopheryl acetate 0.2 to 0.4 Water Qsp 100

[0112] Daily application of the composition according to the invention to the skin and, in particular, areas of skin comprising melanocytes whose mitochondrial function is altered makes it possible to delay the appearance of new lesions and to stabilize existing lesions in subjects at an early stage of vitiligo.

Claims

Claims

1. A composition for use in the prevention and / or treatment, in a subject, of the early stage of vitiligo corresponding to the deregulation of the mitochondrial function of keratinocytes and melanocytes associated with an abnormally high level of ROS within these mitochondria, which composition comprises at least one strain of Bifidobacterium longum or Bifidobacterium breve, or a lysate thereof.

2. The composition according to claim 1, characterized in that said composition aims to prevent or treat a patient suffering from vitiligo.

3. The composition according to any one of the preceding claims, characterized in that said at least one strain of Bifidobacterium longum or Bifidobacterium breve is present in the form of a lysate, preferably said lysate is obtained by ultrasonic lysis.

4. The composition according to any one of the preceding claims 5, characterized in that the content of the composition according to the invention in lysate of said at least one strain of Bifidobacterium is between 1 and 20% (by weight relative to the total weight of the composition), preferably it is between 5 and 10%.

5. The composition according to any one of the preceding claims, characterized in that it further comprises at least one antioxidant.

6. The composition according to claim 5, characterized in that said antioxidant is chosen from sinapine and its derivatives.

7. The composition according to the preceding claim, characterized in that the sinapine derivatives have the formula (II): o > (II) % ' ■■ ■ " o ■ ■ ■■ RsÔ In which - R1 and R3 are independently chosen from a hydrogen atom or a C1 to C8 alkyl group, preferably a C1 to C4 alkyl group and, particularly preferably, a C1 to C2 alkyl group; and - R2 is independently chosen from a hydrogen atom or a C1 to C8 alkyl group, preferably a C1 to C4 alkyl group C1 to C4 and, particularly preferably, a C1 to C2 alkyl group.

8. The composition according to claim 6, characterized in that the sinapine is in the form of an extract of seeds or germs of a plant belonging to the Brassicaceae family.

Images