Use of rhamnolipid(s) to prevent discoloration of skin blackheads

Abstract

Use of rhamnolipid(s) to prevent the discoloration of cutaneous blackheads. The present invention relates to the cosmetic use of at least one di-rhamnolipid of the general formula (I): (I) as well as their salts, solvates, and optical isomers, to reduce and / or inhibit the development of color, for example brown or black, of cutaneous comedones and / or prevent the appearance of cutaneous blackheads. It also relates to a non-therapeutic cosmetic method for reducing and / or inhibiting the development of color, for example brown or black, of cutaneous comedones and / or preventing the appearance of cutaneous blackheads, comprising the topical application to the skin of a composition comprising said active ingredient. Figure for the abstract: None

Description

Title of the invention: Use of rhamnolipid(s) to prevent the coloration of skin blackheads Technical field

[0001] The present invention relates to the field of cosmetic products, in particular intended for the prevention of skin blackheads and in particular for inhibiting the appearance of the black or brown color of skin comedones.

[0002] More particularly, the present invention aims to propose the non-therapeutic cosmetic use of a specific active ingredient as an inhibitor of the black or brown coloration of comedones.

[0003] It also relates to a non-therapeutic cosmetic process for reducing and / or inhibiting the development of the color, for example brown or black, of cutaneous comedones and / or preventing the appearance of cutaneous blackheads comprising the topical application to the skin of a composition comprising said active ingredient.

[0004] For the purposes of the present invention, the term "skin" means the entire skin of the body, excluding the scalp and mucous membranes. Preferably, the skin refers to the skin of the face and / or hands, in particular the skin of the face, more particularly the skin of the forehead and / or the wings of the nose and / or the chin. Prior art

[0005] There are cosmetic compositions to combat the appearance of blackheads on the skin or to mask them, particularly on the face. This type of skin imperfection, which affects all skin types, is in fact most often considered unsightly and therefore undesirable. Given its black or even brown color, it is considered too visible, especially on skin with little pigmentation.

[0006] To date, the origin of the color of the skin blackhead has not been fully established.

[0007] On the other hand, it is known that the cutaneous blackhead comes from the process of come- dogenesis which affects the pilosebaceous units of the sebaceous follicle type, which are distributed mainly on the face.

[0008] Clinically, a cutaneous blackhead is therefore an open comedo (non-inflammatory lesion) characterized by distension of the hair canal, sebum retention and excessive cornification of the pilosebaceous canal. Hypercornification would lead to sebum retention and the accumulation of cellular debris.

[0009] A number of solutions for treating skin blackheads have already been proposed.

[0010] Some of these solutions are based more specifically on the treatment of blackheads with an active ingredient capable of preventing, altering or eliminating blackheads. As a illustrative of these active ingredients, mention may in particular be made of active ingredients capable of solubilizing lipids constituting blackheads such as alkyl lactate derivatives, described in patent US 4,540,567, the lipase enzyme, described in application US 2006 / 00511339, or even neutralized fatty acids such as described in application EP 3,150,187. A certain number of these active ingredients, however, have the disadvantage of altering the organoleptic properties of the composition comprising them, in particular the odor and / or the color of the composition, over time. These active ingredients also prove effective only with regard to blackheads which are already evident.

[0011] Furthermore, other solutions available today act by mechanical extraction or use laser energy (LED).

[0012] As for the extraction method, it is based on the use, for example, of a comedone vacuum, a comedone extractor or a self-adhesive patch to be removed after a few minutes of contact with the skin to be treated. It clearly has the disadvantages of being painful and of generating redness or irritation.

[0013] The present invention has the particular object of proposing new active ingredients which are particularly effective with regard to the development of blackheads but free from the aforementioned drawbacks.

[0014] For the purposes of the present invention, the treatment of skin blackheads aims to reduce or even inhibit the development of the black or brown color of comedones and thereby to prevent the appearance of skin blackheads. Summary of the invention

[0015] Thus, according to a first aspect, the present invention relates to the cosmetic use of at least one di-rhamnolipid of general formula (I):

[0016] [Chem.l]

[0017] in which: - m = 2, 1 or 0, - n = 1, and - R1 and R2, independently of each other, are hydrocarbon radicals, identical or different, having from 2 to 24, preferably from 5 to 13 carbon atoms, optionally branched, optionally substituted, in particular hydroxy-substituted, optionally unsaturated, in particular a mono-, di- or tri-unsaturated alkyl radical, as well as their salts, their solvates, and their optical isomers, to reduce and / or inhibit the development of color, for example brown or black, of skin comedones and / or prevent the appearance of skin blackheads.

[0018] The invention further relates to a cosmetic process for reducing and / or inhibiting the development of black or brown coloration of comedones, in particular for preventing the formation of blackheads, comprising the topical application to the skin of a cosmetic composition comprising at least one di-rhamnolipid of general formula (I).

[0019] It also relates to a cosmetic process for reducing and / or inhibiting the development of the black or brown color of cutaneous comedones and / or for preventing the appearance of blackheads, comprising: a) a step of topical application to the skin of a washing solution; b) a step of topical application to the skin of a cosmetic composition comprising at least one di-rhamnolipid of general formula (I), and c) preferably, a step of topical application of a composition different from the composition applied in step c) and containing at least one active ingredient distinct from said di-rhamnolipid.

[0020] Steps b) and c) can be carried out simultaneously or successively.

[0021] Against all expectations, rhamnolipids have in fact been characterized by the inventors as being capable of inhibiting the black or brown coloration of comedones and therefore of preventing the appearance of cutaneous blackheads.

[0022] More specifically and as is apparent from the examples below, the inventors have found that di-rhamnolipids inhibit the formation of cutaneous blackheads by probably intervening at the level of the oxidation process of L-DOPA (3,4-dihydroxy-L-phenylalanine). As a reminder, L-DOPA is involved in the very complex mechanism of melanogenesis. More specifically, the oxidation of L-DOPA, promoted by the microbial activity present in the comedo, is manifested by a color effect probably of the dopachrome type, the latter being a colored intermediate of the melanin biosynthesis pathway. The di-rhamnolipids in accordance with the invention apparently alter the formation of the product of the oxidation reaction in the comedones, and therefore inhibit the black or brown coloration of the latter. This effectiveness of the di-rhamnolipids is, to the inventors' knowledge, characterized for the first time.

[0023] First discovered by Bergstrôm in 1946, rhamnolipids are in fact primarily known as surfactants with high stability and high antibacterial and antifungal activity. Thus, they are mainly used as biosurfactants in cosmetic compositions (US 2014 / 0296168 A1, EP 2 786 742 A1 and US 2020 / 0069779 A1). More recently, WO 2020 / 178048 proposed the use of rhamnolipids as an aid for depositing at least one substance on a surface, such as hair, and the use of rhamnolipids as an active ingredient in skincare products to reduce skin reactivity and redness has also been suggested (EP 3 338 763 A1 and EP 3 338 762 A1). However, none of the aforementioned applications are intended for the use considered by the invention.

[0024] It is also important to discriminate between the reduction and / or inhibition of the black or brown coloration of the comedones targeted according to the invention and a skin depigmentation and / or whitening type action as described above. These are clearly two different applications with distinct modes of action. Thus, the depigmentation of the skin is achieved by inhibition of the human melanin biosynthesis pathway, in particular via inhibition of the expression of Tyrosinase, whereas the inhibition of the brown or black coloration of the comedones is achieved, as mentioned above, by alteration of the formation of dopachrome.

[0025] More precisely, an inhibitor of the black or brown coloration of comedones is, within the meaning of the present invention, a compound capable of slowing down, or even inhibiting the appearance of the black or brown color of comedones. In particular, a compound is considered to be an inhibitor of the black or brown coloring of comedones if the percentage of inhibition on the development of the color is at least 15%, preferably at least 20%, more particularly at least 25%, in particular as evaluated according to the protocol detailed in the examples below.

[0026] The cosmetic uses and methods considered according to the invention are non-therapeutic.

[0027] Preferably, the skin is the skin of the face and / or body, in particular the face and / or hands, preferably the face, and more particularly the forehead and / or the wings of the nose and / or the chin.

[0028] According to a first variant, the skin is oily and / or shiny skin, in particular skin exhibiting excessive secretion and excretion of sebum. According to this variant, the skin is in particular oily and / or shiny skin, in particular of phototype 1, 2, 3 or 4, in particular oily and / or shiny skin of the face and / or hands, more particularly oily and / or shiny skin of the forehead, and / or the wings of the nose and / or the chin.

[0029] According to a second variant, the skin is healthy skin devoid of the clinical manifestations of acne, namely acne lesions, such as the presence of numerous acne spots. Indeed, blackheads constitute cutaneous imperfections of the skin, distinct from skin conditions, such as acne. In particular, the blackhead is not an inflammatory lesion of the skin as opposed to the lesions characteristic of acne. Moreover, the areas of the face, conducive to the development of blackheads, namely more particularly the wings of the nose, do not constitute precisely preferred areas for the development of acne. Detailed description RHAMNOLIPIDS

[0030] Rhamnolipids are glycolipids produced by various bacterial species. They consist of one rhamnose fragment (mono-rhamnolipid) or two rhamnose fragments (di-rhamnolipid), linked by a glycosidic bond to one, two or three [3-hydroxy] fatty acid chains linked together by an ester bond.

[0031] More precisely, these mono- and di-rhamnolipids correspond to the following general formula:

[0032] [Chem. 2]

[0033]

[0034]

[0035]

[0036] in which: - m = 2, 1 or 0, - n = 1 or 0, and - R1 and R2, independently of each other, are hydrocarbon radicals, identical or different, having from 2 to 24, preferably from 5 to 13 carbon atoms, optionally branched, optionally substituted, in particular hydroxy-substituted, optionally unsaturated, in particular a mono-, di- or tri-unsaturated alkyl radical. Thus, when n is zero, general formula (I) protects mono-rhamnolipids and when n is 1, it protects di-rhamnolipids. As regards the present invention, it particularly relates to the use of at least one di-rhamnolipid of general formula (I): [Chem. 3] (I)

[0037] in which: - m = 2, 1 or 0; -n = 1 ; - R1 and R2, independently of one another, are identical or different hydrocarbon radicals having from 2 to 24, preferably from 5 to 13 carbon atoms, optionally branched, optionally substituted, in particular hydroxy-substituted, optionally unsaturated, in particular a mono-, di- or tri-unsaturated alkyl radical; as well as their salts, their solvates, and their optical isomers, for reducing and / or inhibiting the development of color, for example brown or black, of cutaneous comedones and / or preventing the appearance of cutaneous blackheads.

[0038] Since n is equal to 1 in the general formula (I), the corresponding compounds suitable for the invention are also called di-rhamnolipids in the present description. The glycosidic bond between the two rhamnose fragments can be in alpha or beta configuration, and is preferably in alpha configuration.

[0039] In the context of the invention, - the salts of the di-rhamnolipids of formula (I) are more particularly their carboxylate salts with an organic or inorganic cation and in particular with a cation chosen from sodium, potassium, calcium and ammonium, - the solvated forms of the di-rhamnolipids of formula (I) are more particularly those solvated with one or more molecules of water or organic solvents, for example a hydrate or a solvate of linear or branched alcohol such as ethanol or isopropanol, the optically active carbon atoms of the fatty acids are preferably in the form of R-enantiomers, and - an “alkyl” radical, a saturated, linear or branched aliphatic group; for example, a C1-C2o-alkyl group represents a hydrocarbon chain of 1 to 20 carbon atoms, linear or branched, more particularly a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl.

[0040] In particular, the use according to the invention implements at least one di-rhamnolipid of general formula (I), in which R1 and R2, identical or different, are chosen from the pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl radicals and the radicals of formula -(CH2)OCH3 with o being an integer ranging from 1 to 23, in particular from 3 to 15 and more particularly from 4 to 12.

[0041] According to a variant of the invention, the present invention aims at the use of at least a di-rhamnolipid of general formula (I) in which m is equal to 1.

[0042] According to a variant of the invention, the claimed use uses said di-rhamnolipid of general formula (I) in the form of a mixture of at least two and preferably at least three di-rhamnolipids of general formula (I) in which m is preferably equal to 1.

[0043] According to another variant of the invention, said di-rhamnolipid of formula (I) is implemented in the form of a mixture comprising at least one mono-rhamnolipid.

[0044] More particularly, the claimed use uses at least one di-rhamnolipid compound, of formula (II):

[0045] [Chem.4] O OH " (II)

[0046] in which: - m = 2, 1 or 0, and preferably m = 1, -n = 1, - Ri is a radical -(CH2)P-CH3, with p being an integer ranging from 1 to 23, preferably from 4 to 12, - R2 is a radical -(CH2)q-CH3, with q being an integer ranging from 1 to 23, preferably from 4 to 12, as well as their salts, solvates, and optical isomers.

[0047] By way of illustration and non-limiting example of the di-rhamnolipids of formula (II) which may be suitable for the invention, mention may in particular be made of the compounds of formula Di-RL-CXCY, as defined in Table 1 below.

[0048] The formula Di-RL-CXCY is an alternative writing to represent a di-rhamnolipid (Di-RL) functionalized by two radicals Ri and R2 respectively represented by the symbols CX and CY, the integers X and Y being respectively equal to p+4 and q+4.

[0049] [Tables 1] Di-RL-CY compounds 2 10 B ii | dEMHCÏ4 10 10 11 10 12 13 «L-C16C14 12 10 13 diRL-C16C16 12 12

[0050] Advantageously, the di-rhamnolipid used according to the invention is at least one di-rhamnolipid of formula (II), in which p and q are identical and equal to 6 and m is equal to 1, also called di-RL-ClOCIO, or one of its salts, solvates and optical isomers.

[0051] According to an advantageous embodiment, this di-rhamnolipid of formula (II) in which p and q are identical and equal to 6 and m is equal to 1 is implemented in the form of a mixture of rhamnolipids, comprising it in a proportion of at least 50% by weight, and preferably from 51% to 85% by weight, relative to the total weight of rhamnolipids.

[0052] According to another advantageous embodiment, the di-rhamnolipid used according to the invention is at least one di-rhamnolipid of formula (II), in which m is equal to 1, p is equal to 6, q is equal to 8, or one of its salts, solvates, and optical isomers.

[0053] According to another advantageous embodiment, the di-rhamnolipid used according to the invention is a di-rhamnolipid of general formula (I) in which m is equal to 1, Ri is a radical -(CH2)OCH3 with o being an integer ranging from 4 to 12, and R2 is chosen from the radicals pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, un-decenyl, dodecenyl, tridecenyl, and preferably Ri is a radical -(CH2)6CH3 and R2 is a nonenyl radical, or one of its salts, solvates, and optical isomers.

[0054] According to another preferred embodiment, the di-rhamnolipid considered according to the invention is implemented in the form of a mixture of rhamnolipids comprising at least two, in particular at least three di-rhamnolipids of formula (II) or of formula (I) chosen from: - a di-rhamnolipid of formula (II), in which p and q are identical and equal to 6 and m is equal to 1, - a di-rhamnolipid of formula (II) in which m is equal to 1, p is equal to 6, q is equal to 8, and - a di-rhamnolipid of general formula (I) in which m and n are equal to 1, Ri is a radical (CH2)OCH3 with o being an integer ranging from 4 to 12, and R2 is chosen from the radicals pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, and preferably R^st a radical -(CH2)6CH3and R2 is a nonenyl radical.

[0055] In a particularly advantageous manner, the di-rhamnolipid considered according to the invention is implemented in the form of a mixture of rhamnolipids comprising at least two, in particular at least three di-rhamnolipids of formula (II) or of formula (I) chosen from: - at least 50% by weight, preferably from 51% to 85% by weight of a di-rhamnolipid of formula (II) in which p and q are identical and equal to 6 and m is equal to 1 relative to the total weight of rhamnolipids, - from 0.5% to 25% by weight, preferably from 5% to 15% by weight of a di-rhamnolipid of formula (II) in which p is equal to 6, q is equal to 8 and m is equal to 1 relative to the total weight of rhamnolipids, and - from 0.5% to 15% by weight, preferably from 3% to 12% by weight, preferably from 5% to 10% by weight of a di-rhamnolipid of general formula (I) in which n and m are equal to 1, Ri is a radical -(CH2)6CH3 and R2 a nonenyl radical, relative to the total weight of rhamnolipids.

[0056] As specified above, rhamnolipids are conventionally prepared by methods known to those skilled in the art from producing bacteria, such as Pseudomonas.

[0057] Suitable fermentation methods are reviewed in D. Haferburg, R. Hommel, R. Claus and H.P. Kleber in Adv Biochem. Ing. / Biotechnol. (1986) 33, 53-90 and by F. Wagner, H. Bock and A. Kretschmar in Fermentation (ed. R.M. Lafferty) (1981), 181-192, Springer Verlag, Vienna.

[0058] As di-rhamnolipids, one can use the one sold under the name RHEANCE One by the company EVONIK (INCI name: glycolipids).

[0059] Advantageously, said di-rhamnolipid of general formula (I) or one of its mixtures, in particular as detailed above, is implemented in the form of a topical cosmetic composition containing it. Such a composition contains preferably from 0.01% to 10% by weight, preferably from 0.1% to 5% by weight, even better from 0.3% to 3% by weight of di-rhamnolipid(s) of general formula (I) relative to the total weight of the cosmetic composition. COMPOSITION

[0060] In addition to said di-rhamnolipid, a composition according to the invention further comprises a physiologically acceptable medium.

[0061] Such an environment is considered physiologically acceptable when it does not generate tingling, pulling or unacceptable discomfort for the user.

[0062] A composition used according to the invention can be presented in all the galenic forms normally used in the cosmetic field.

[0063] It may be in particular in the form of an aqueous, hydroalcoholic, optionally gelled solution, a dispersion of the lotion type, optionally two-phase, an oil-in-water or water-in-oil or multiple emulsion, an aqueous gel, a dispersion of oils in an aqueous phase, in particular using spherules, these spherules being able to be polymeric particles or better, lipid vesicles of ionic and / or non-ionic type, or even in the form of a powder, a serum, a paste or a flexible stick or even a stick. It may be of solid, pasty, or more or less fluid liquid consistency.

[0064] According to a preferred variant, the composition considered according to the invention is distinguished from compositions intended essentially as detergents for the skin, hair and / or mucous membranes, such as soaps, shampoos and shower gels for washing and / or cleaning.

[0065] A composition according to the invention may comprise all the constituents usually used in the application and topical administration envisaged.

[0066] A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersion of an aqueous phase in a fatty phase (W / O) or of a fatty phase in an aqueous phase (O / W), of liquid or semi-liquid consistency of the milk type, or of soft, semi-solid or solid consistency of the cream or gel type, or even of multiple emulsion (W / O / W or O / W / O). These compositions are prepared according to the usual methods.

[0067] More particularly, this composition is intended for topical application and preferably comes in the form of an oil-in-water emulsion. Preferably, such an emulsion is not intended to be rinsed after application.

[0068] A composition according to the invention is intended to be applied to skin.

[0069] Preferably, the skin is the skin of the face and / or body, in particular the face and / or hands, preferably the face, and more particularly the forehead and / or the wings of the nose and / or the chin.

[0070] According to a first variant, the skin is oily and / or shiny skin, in particular skin with excessive secretion and excretion of sebum. According to this variant, the skin is in particular oily and / or shiny skin, in particular of phototype 1, 2, 3 or 4, in particular oily and / or shiny skin of the face and / or hands, more particularly oily and / or shiny skin of the forehead, and / or the wings of the nose and / or the chin.

[0071] According to a second variant, the skin is healthy skin devoid of the clinical manifestations of acne, namely acne lesions, such as the presence of numerous acne spots. Indeed, blackheads constitute cutaneous imperfections of the skin, distinct from skin conditions, such as acne. In particular, the blackhead is not an inflammatory lesion of the skin as opposed to the lesions characteristic of acne. Moreover, the areas of the face, conducive to the development of blackheads, namely more particularly the wings of the nose, do not constitute precisely preferred areas for the development of acne.

[0072] A composition used according to the invention may advantageously comprise at least one additional active ingredient.

[0073] It may in particular be at least one active ingredient for the care of oily skin.

[0074] It may also advantageously comprise at least one additional active ingredient for the care of aged skin.

[0075] By the expression "additional active ingredient" is meant, in the context of the present invention, a compound which has by itself, that is to say not requiring the intervention of an external agent to activate it, a biological activity which can be in particular: - a desquamating activity (which allows the opening of comedones), and / or - antimicrobial activity (particularly on C. acnes), and / or - a soothing or anti-irritant activity, and / or - a sebum-regulating or anti-seborrheic activity, and / or - an astringent activity, and / or - an activity intended to combat and / or prevent the signs of aging, particularly chronobiological aging, for example wrinkles and fine lines.

[0076] The additional active agent usable in the compositions of the invention is preferably chosen from desquamating agents, soothing agents, anti-irritant agents, sebum-regulating or anti-seborrheic agents, astringent agents, and their mixtures in all proportions.

[0077] The additional active ingredient for the care of oily skin used in the composition according to the invention may represent from 0.0001% to 20%, preferably from 0.01% to 10% and better still, from 0.01% to 5% by weight, relative to the total weight of the composition.

[0078] Furthermore, a composition used according to the invention may advantageously comprise from 5% to 80% by weight, and preferably from 35% to 75% by weight of water, relative to the total weight of said composition.

[0079] The pH of said composition is advantageously less than or equal to 8, preferably ranging from 4 to 7, even better ranging from 4.5 to 6.5.

[0080] Of course, those skilled in the art will take care to choose the possible additional compound(s), and / or their quantity, in such a way that the advantageous properties of the compound(s) of general formula (I) according to the invention are not, or not substantially, altered by the envisaged addition and that the properties of the resulting compositions are compatible with the topical route of administration.

[0081] A composition of the invention may advantageously have a firm and compact feel when taken. It may be thick upon application and then transform, melt and release freshness.

[0082] As specified, it is advantageously presented in the form of an oil-in-water emulsion, advantageously very fluid.

[0083] A composition may alternatively have the form of a care or makeup product for the face and / or body, and be packaged for example in the form of a cream in a pot or a fluid in a tube or in a pump bottle or in a dropper bottle.

[0084] A composition according to the invention can be manufactured by any known process generally used in the cosmetic field.

[0085] The ingredients are mixed before being shaped, in the order and under conditions easily determined by those skilled in the art.

[0086] According to a particular embodiment of the invention, other agents intended to enhance the appearance and / or texture of the skin may also be added to the composition according to the invention. COSMETIC PROCESSES

[0087] As mentioned previously, the present invention relates to a cosmetic process for reducing and / or inhibiting the development of black or brown coloration of comedones, in particular for preventing the formation of blackheads, comprising the topical application to the skin of a cosmetic composition comprising at least one di-rhamnolipid of general formula (I).

[0088] The cosmetic process of the invention is carried out by administering topically a composition comprising at least one di-rhamnolipid of general formula (I), preferably in a physiologically acceptable medium.

[0089] Topical administration consists of the external application to the skin of cosmetic compositions according to the usual techniques for using these compositions.

[0090] By way of illustration, the cosmetic process according to the invention can be implemented by topical application, for example daily, of at least one di-rhamnolipid of general formula (I) and in particular one of its mixtures in particular as detailed above, which may for example be formulated in the form of a cream, gel, serum, lotion, emulsion, cleansing milk, stick or after-sun composition, preferably in the form of an emulsion.

[0091] According to one embodiment, the application is repeated for example 1 to 2 times daily over one day or more and generally over a prolonged period of at least 4, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.

[0092] According to another embodiment, the application is daily (once a day) and generally over a prolonged period of at least 4, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.

[0093] According to another embodiment, the composition containing at least one di-rhamnolipid of general formula (I) or one of its mixtures as defined previously will be applied to areas of skin previously cleaned, for example using a suitable soap, and / or previously freed from blackheads, for example using an adhesive patch or mechanical action.

[0094] According to an alternative embodiment, the composition containing at least one di-rhamnolipid as defined above, will be applied to areas of skin previously cleaned using a washing solution, where appropriate itself comprising at least one rhamnolipid, and in particular a di-rhamnolipid.

[0095] Furthermore, treatment combinations with possibly topical forms may be envisaged in order to supplement or reinforce the activity of the di-rhamnolipid of general formula (I).

[0096] One could imagine a topical treatment with a composition containing at least one di-rhamnolipid of general formula (I), associated with an additional composition dedicated to topical application and containing at least one active ingredient distinct from the di-rhamnolipid of general formula (I).

[0097] Thus, the present invention relates in particular to a cosmetic process for reducing and / or inhibiting the development of the black or brown color of cutaneous comedones and / or for preventing the appearance of blackheads, comprising: a) a step of topical application to the skin of a washing solution; b) a step of topical application to the skin of a cosmetic composition comprising at least one di-rhamnolipid of general formula (I) or (II) as defined above, in particular in the form of an oil-in-water emulsion; and c) preferably, a step of topical application of a composition different from the composition applied in step b), and containing at least one active ingredient distinct from the di-rhamnolipid of general formula (I) or (II), steps b) and c) can be carried out simultaneously or successively.

[0098] Such a composition applied in step c) can be described as a “composition annex”.

[0099] The skin considered in the method is the skin of the face and / or body, in particular the face and / or hands, preferably the face, and more particularly the forehead and / or the wings of the nose and / or the chin.

[0100] The washing solution may in particular be in different forms, such as a solution, an aqueous solution, a lotion, a milky lotion, a cream, a gel, a liquid gel, a paste, a serum, a suspension, a dispersion, a fluid, a milk, an emulsion (O / W or W / O form), or others, preferably in the form of an aqueous solution or gel.

[0101] In an alternative embodiment, the washing composition of step a) may contain a di-rhamnolipid of general formula (I), and in particular at least one di-rhamnolipid of general formula (I), or even of formula (II), or better of formula (II) in which p and q are identical and equal to 6.

[0102] As regards the additional composition, different from the composition used according to the invention because it is free of di-rhamnolipid of formula (I), it can be in the form of an oil-in-water emulsified gel, comprising at least one polyol; at least one hydrophilic gelling agent; at least one derivative of polyethylene glycol and mono-, di- and tri-glycerides of acid comprising at least one alkyl chain ranging from C6 to C16, and having at least two ethylene oxide groups; at least one non-volatile ether oil having from 10 to 40 carbon atoms; and at least one non-volatile monoester oil.

[0103] Throughout the description, including the claims, the expressions "between ... and ..." and "ranging from ... to ..." must be understood inclusively, unless otherwise specified.

[0104] The following examples illustrate the present invention without limiting its scope. Examples

[0105] Methodology on a reconstructed epidermis to characterize the appearance of dark-colored structures and their development over time

[0106] For the purposes of the present invention, the term “dark-colored structures” means the structures responsible for the coloring of blackheads.

[0107] This method aims to characterize the evolution over time of the colon manifestation, induced by an intracellular extract of bacteria of the Cutibacterium acnes type (formerly listed under the name Propionibacterium acnes) in the presence of 3,4-dihydroxy-L-phenylalanine (L-DOPA), deposited on the surface of a reconstructed EpiSkin™ epidermis.

[0108] To do this, an intracellular extract of bacteria of the Cutibacterium acnes CIP 53.117 type stored at 4°C in lyophilized form, is suspended in PBS IX (Dulbecco's Phosphate Buffered Saline supplied by GIBCO BRL, Life Technologies) at a concentration of 6 mg / mL. This extract is then deposited on the surface of an EPISKIN epidermis in the presence of 3,4-dihydroxy-L-phenylalanine (L-DOPA - supplied by Sigma Aldrich) at 1 mg / mL.

[0109] The manifestation of a color effect and its development towards a dark color are observed visually, from 48 hours of incubation.

[0110] In vitro methodology used for the evaluation of the inhibition capacity of the color development

[0111] This method is based on the measurement of absorbance, over time, carried out directly on a composition formed from a mixture of intracellular extract of bacteria of the Cutibacterium acnes type, 3,4-dihydroxy-L-phenylalanine (L-DOPA), and the compound to be tested.

[0112] The measurements are compared to those carried out for a mixture of an intracellular extract of bacteria of the Cutibacterium acnes type, and 3,4-dihydroxy-L-phenylalanine (L-DOPA), in the absence of the compound to be tested (reference).

[0113] The method is adapted from an enzymatic assay method for ty-rosinase activity (Behbahani et al., Microchemical Journal (1993) 47, 251) which is based on the absorbance properties at 475 nm of a colored intermediate in the melanin biosynthesis pathway from L-DOPA, namely dopachrome, an oxidation product of L-DOPA. Preparation of the reference composition

[0114] An intracellular extract of bacteria of the type Cutibacterium acnes CIP 53.117 stored at 4°C in lyophilized form is suspended in PBS IX (supplied by GIBCO BRL, Life Technologies) at a concentration of 6 mg / mL.

[0115] A solution of L-DOPA at a concentration of 0.5 mg / mL is prepared by bringing together L-DOPA (supplied by Sigma Aldrich) with milliQ water so as to have an L-DOPA concentration of 1 mg / mL, then diluted with PBS IX (Dulbecco's Phosphate Buffered Saline supplied by GIBCO BRL, Life Technologies).

[0116] Mixing 50 pL of these two solutions and 100 pL of PBS IX (Dulbecco's Phosphate Buffered Saline supplied by GIBCO BRL, Life Technologies) results in a composition with a total volume of 200 pL containing L-DOPA (at a concentration of 125 pg / mL) and Cutibacterium acnes extract (at a concentration of 1.5 mg / mL).

[0117] Preparation of a composition 1 comprising only an extract of Cutibacterium acnes

[0118] Cutibacterium acnes extract at 6 mg / mL was diluted with PBS IX (Dulbecco's Phosphate Buffered Saline supplied by GIBCO BRL, Life Technologies) so as to form a composition of 200 pL at a concentration of 1.5 mg / mL of Cuti-bacterium acnes.

[0119] Preparation of a composition 2 comprising only L-DOPA

[0120] The 0.5 mg / mL L-DOPA solution was also diluted with PBS 1X (Dulbecco's Phosphate Buffered Saline supplied by GIBCO BRL, Life Technologies) to form a 200 pL composition at a concentration of 125 pg / mL L-DOPA. Absorbance measurement

[0121] The compositions to be tested and the reference composition are introduced separately into wells of a 96-well microplate suitable for reading in visible spectrophotometry, and placed at a temperature of 32°C.

[0122] The formation of a colored product is then monitored over time by spectrophotometry. To do this, the absorbance, or optical density (OD), is measured at 475 nm from time 0 to time 2 hours using a Spectra Max M5e reader and Spectra Max software (time 0 corresponds to the addition of composition 1 or the introduction of the composition into the wells).

[0123] The formation of a colored product is visually observed for the reference composition, an oxidation product of L-DOPA.

[0124] On the other hand, no significant color effect was noted over time for compositions 1 and 2 comprising respectively an extract of Cutibacterium acnes alone and L-DOPA alone.

[0125] This confirms the catalytic activity of the bacterial extract of Cutibacterium acnes on the development of dark color by oxidation of L-DOPA.

[0126] It is thus possible to follow the formation of the colored intermediate of the melanin biosynthesis pathway thanks to its absorption properties at 475 nm. The effectiveness of a compound in preventing the development of the color of skin blackheads can be evaluated by this means.

[0127] Parameters studied for F evaluation of F effectiveness of the different compounds a test

[0128] The color development inhibition capacity of a given compound was assessed by comparing the absorbance measurements obtained for the test compositions with those obtained for the reference composition.

[0129] More precisely, the inhibitory effect of the test compound was evaluated by comparing the initial rate of oxidation of L-DOPA under the action of the bacterial extract at 475 nm for the test composition with that of the reference composition in order to obtain a corresponding percentage of inhibition.

[0130] In practice, the initial rate (Vi) of the oxidation reaction is calculated from the linear part of the curve of the graph of absorbance values. This part is between 10 and 40 minutes, the initial rate of the oxidation reaction is determined using the following relationship:

[0131] [Math.l] D. 0. measured at 40 minutes — DO measured at 10 minutes VI = -------------------------------------------------- 30 minutes

[0132] The percentage inhibition (%inhib) of a given compound on the formation of the colored product is then obtained using the initial rate values ​​of the oxidation reaction for the reference composition (Viref) and for the test composition (Vitest) according to the following relationship:

[0133] [Math.2] %inhib = --——----— V^ref

[0134] For the purposes of the invention, a compound is considered to have an inhibitory effect if the value of %inhib is at least 15%.

[0135] Example 1 - In vitro evaluation of the capacity of a di-rhamnolipid in accordance with the invention to inhibit the development of color

[0136] Three test compositions 1, 2 and 3 comprising at least one di-rhamnolipid of general formula (I), RL, (reference RheanceOne® from the company Evonik) at respective concentrations of 1.25, 2 and 2.5 mg / ml were prepared. These compositions, with a total volume of 200 μl, also contain L-DOPA (25 μg), the Cutibacterium acnes extract (0.3 mg) and the PBS buffer mentioned in the methodology section above. The change in the optical density at 475 nm of these three compositions, as well as of the reference composition, is then measured according to the protocol indicated in the methodology section which is presented above.

[0137] The measured optical density values ​​are collected in the following table.

[0138] [Tables2] Duration (in months) § W % 40 50 80 CsKipc-sih0E.de resêrsBse Value of OD 0.6440 0.0450 0.9476 8.0485 0.0565 0.0536 0.0556 6.0567 0.0567 Compsatiœ test1 (1.25 mgM RL) Value of OD 0.0441 0.0451 0.0465 0.0478 0.0504 0.0532 0.0563 0.0575 3.0592 Çcompœàiou «2 (2 mg:W RL) Value of OD 0.0434 0.0440 0.0451 0.0460 0.0483 0.0504 0.0532 0.0546 0.0570 test 3 (2.5 mg / ml RL) OD value 0.0433 0.0441 0.0453 0.0462 0.0475 0.0506 0.0519 0.0534 0.054g

[0139] The percentage inhibition values, calculated from the mathematical formulas detailed in the methodology section above, are presented in Table 3 below.

[0140] [Tables3] Composition Test composition. 1 (1.25 mg / ml RL) Test composition 2 (2 mg / ml RL) Test composition 3 (2.5 mg / ml RL) %inhibition 3.6% 21.8% 38.18%

[0141] It is indeed observed that the effectiveness of the di-rhamnolipid of general formula (I) increases with the RL concentration, up to more than 38% with an RL concentration of 2.5 mg / mL.

[0142] Example 2 - Cosmetic compositions comprising at least one di- rham- nolipid in accordance with the invention

[0143] A composition for topical application is prepared comprising:

[0144] [Tables4] Compound (INCI Name) Xanihane gum 0.5% by weight Glycerin 2% by weight Pheoxyethaiiol 0.5% by weight di-imnolipid of general formula (T) (RheanceQne® from the company Evosiik) 1% by weight Water Qsp 100%

[0145] The composition applied to the skin makes it possible to inhibit the appearance of coloring black or brown comedones.

Claims

1. Claims Cosmetic use of at least one di-rhamnolipid of general formula (I): n

2.

3. in which: - m = 2, 1 or 0, - n = 1, and - R1 and R2, independently of each other, are hydrocarbon radicals, identical or different, having from 2 to 24, preferably from 5 to 13 carbon atoms, optionally branched, optionally substituted, in particular hydroxy-substituted, optionally unsaturated, in particular a mono-, di- or tri-unsaturated alkyl radical, as well as their salts, their solvates, and their optical isomers, for reducing and / or inhibiting the development of the color, for example brown or black, of skin comedones and / or preventing the appearance of skin blackheads. Use according to claim 1, of at least one di-rhamnolipid of general formula (I), in which R1 and R2, identical or different, are chosen from the radicals pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl and the radicals of formula -(CH2)OCH3 with o being an integer ranging from 1 to 23, in particular from 3 to 15 and more particularly from 4 to 12. Use according to claim 1 or 2, of at least one di-rhamnolipid of general formula (I) in which m is equal to 1. Use according to any one of the preceding claims, in

5. wherein said di-rhamnolipid of general formula (I) is implemented in the form of a mixture of at least two and preferably at least three di-rhamnolipids of general formula (I) in which m is preferably equal to 1. Use according to any one of the preceding claims, of at least one di-rhamnolipid compound, of formula (II):

6. in which: - m = 2, 1 or 0, and preferably m = 1, -n = 1, - Ri is a radical -(CH2)P-CH3, with p being an integer ranging from 1 to 23, preferably from 4 to 12, - R2 is a radical -(CH2)q-CH3, with q being an integer ranging from 1 to 23, preferably from 4 to 12, as well as their salts, their solvates, and their optical isomers. Use according to the preceding claim, of at least one di-rhamnolipid compound, of formula (II), in which p and q are identical and equal to 6 and m is equal to 1 or one of its salts, solvates, and optical isomers, preferably the di-rhamnolipid of formula (II) in which p and q are identical and equal to 6 and m is equal to 1 is used in the form of a mixture of rhamnolipids, comprising it in a proportion of at least 50% by weight and preferably from 51% to 85% by weight relative to the total weight of rhamnolipids. Use according to claim 5, of at least one di-rhamnolipid compound of formula (II) in which m is equal to 1, p is equal to 6,

8.

9.

10. q is equal to 8, or one of its salts, solvates, and optical isomers. Use according to any one of claims 5 to 7, wherein said di-rhamnolipid of formula (I) is implemented in the form of a mixture of rhamnolipids comprising at least two, in particular at least three di-rhamnolipids of formula (II) or of formula (I) chosen from: - a di-rhamnolipid of formula (II), in which p and q are identical and equal to 6 and m is equal to 1, -a di-rhamnolipid of formula (II) in which m is equal to 1, p is equal to 6, q is equal to 8, and - a di-rhamnolipid of general formula (I) in which m and n are equal to 1, Ri is a radical -(CH2)OCH3 with o being an integer ranging from 4 to 12, and R2 is chosen from the radicals pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tri-decenyl, and preferably Ri is a radical -(CH2)6CH3 and R2 is a nonenyl radical. Use according to any one of claims 5 to 8, wherein said di-rhamnolipid of formula (I) is implemented in the form of a mixture of rhamnolipids comprising at least two, in particular at least three di-rhamnolipids of formula (II) or of formula (I) chosen from: - at least 50% by weight, preferably from 51% to 85% by weight of a di-rhamnolipid of formula (II) in which p and q are identical and equal to 6 and m is equal to 1 relative to the total weight of rhamnolipids, - from 0.5% to 25% by weight, preferably from 5% to 15% by weight of a di-rhamnolipid of formula (II) in which p is equal to 6, q is equal to 8 and m is equal to 1 relative to the total weight of rhamnolipids, and - from 0.5% to 15% by weight, preferably from 3% to 12% by weight, preferably from 5% to 10% by weight of a di-rhamnolipid of general formula (I) in which n and m are equal to 1, R1 is a radical -(CH2) 6CH3 and R2 a nonenyl radical, relative to the total weight in rhamnolipids. Use according to any one of the preceding claims, in which said di-rhamnolipid of formula (I) is used in a topical cosmetic composition in an amount of 0.01% to 10% by weight, preferably 0.1% to 5% by weight, even better 0.3% to 3% by weight of di-rhamnolipid(s) of general formula (I) relative to the total weight of the cosmetic composition.

11. Use according to any one of the preceding claims, wherein said cosmetic composition is intended for topical application and preferably is in the form of an oil-in-water emulsion.

12. Cosmetic process for reducing and / or inhibiting the development of the black or brown color of cutaneous comedones and / or for preventing the appearance of blackheads, comprising: a) a step of topical application to the skin of a washing solution; b) a step of topical application to the skin of a cosmetic composition comprising at least one di-rhamnolipid of general formula (I) or (II) according to any one of claims 1 to 11, in particular in the form of an oil-in-water emulsion; and c) preferably, a step of topical application of a composition different from the composition applied in step b) and containing at least one active ingredient distinct from said di-rhamnolipid of general formula (I) or (II); said composition comprising at least one di-rhamnolipid being applied to the skin previously cleaned using said washing solution and steps b) and c) can be carried out simultaneously or successively.

13. Method according to the preceding claim, wherein the skin is the skin of the face and / or body, in particular of the face and / or hands, preferably of the face, and more particularly of the forehead and / or the wings of the nose and / or the chin.

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