COSMETIC PROCESS USING MICRO-NEEDLES

Abstract

COSMETIC PROCESS USING MICRONEEDLES The present invention relates to a cosmetic process for a keratinous substance such as the skin and lips, comprising the steps of: applying, to the keratinous substance, at least one composition comprising at least one cosmetic active substance; and applying, to the keratinous substance, a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet such that the microneedles can penetrate the keratinous substance, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance, wherein the frequency of application of the microneedle sheet to the keratinous substance is 3 times or less per week,and the number of passes of the microneedle sheet over the keratinous substance in each application is 5 or less, provided that, if the frequency of applying the microneedle sheet over the keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance in each application is not 5, and, if the number of passes of the microneedle sheet over the keratinous substance in each application is 5, the frequency of applying the microneedle sheet over the keratinous substance is not 3 times per week. By means of the present invention, the risk of pigmentation due to the use of microneedles can be reduced. Figure for abstract: 2,

Description

Title of the invention: COSMETIC PROCESS USING MICRO-NEEDLES Technical field

[0001] The present invention relates to the use of a plurality of micro-needles for cosmetic treatments of a keratinous substance such as the skin and lips. STATE OF THE ART

[0002] The use of different types of microneedles such as metallic, soluble and hollow microneedles to improve the permeability of cosmetic active substances in the skin is well known. For example, WO 2019 / 100902 discloses a dermo-cosmetic method by transdermal penetration which implements microneedles in a combination of a cosmetic composition including certain cosmetic active substances. In WO 2019 / 100902, the microneedles are used every night for 28 days. DISCLOSURE OF THE INVENTION

[0003] It is known that the use of such microneedles can cause inflammation of the skin and, therefore, a risk of skin pigmentation, known as post-inflammatory hyperpigmentation. This can become particularly important when microneedles are used to treat skin hyperpigmentation, such as melasma, dark circles and brown spots.

[0004] An objective of the present invention is to provide a cosmetic process that uses microneedles that makes it possible to reduce the risk of pigmentation of a keratinous substance, such as the skin and lips, due to the use of the microneedles.

[0005] The above objective can be achieved by a cosmetic process for a keratinous substance such as skin and lips, comprising the steps of:

[0006] - application, on the keratinous substance, of at least one composition comprising at least one cosmetic active substance; and

[0007] - application, on the keratinous substance, of a sheet of micro-needles comprising a substrate sheet and a plurality of microneedles on the substrate sheet such that the microneedles can penetrate the keratinous substance, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance,

[0008] in which

[0009] - the frequency of application of the microneedle sheet to the substance keratinous is 3 times or less per week, and

[0010] - the number of passes of the microneedle sheet over the keratinous substance during each application is 5 or less,

[0011] - provided that

[0012] - if the frequency of application of the microneedle sheet on the substance keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5,

[0013] and

[0014] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0015] The above step of applying the composition comprising at least one cosmetic active substance can be carried out before the step of applying the microneedle sheet to the keratinous substance.

[0016] The cosmetic active substance may be chosen from skin care active substances, preferably chosen from the group consisting of depigmenting or lightening agents, anti-aging agents and mixtures thereof, and more preferably chosen from the group consisting of vitamin B 3 and its derivatives, ascorbic acid and its derivatives, resorcinol derivatives, tranexamic acid and its derivatives, hyaluronic acid substances and mixtures thereof.

[0017] The cosmetic active substance may be chosen from depigmenting or lightening agents, and preferably chosen from the group consisting of niacinamide, phenylethyl resorcinol, tranexamic acid and a mixture thereof.

[0018] The quantity of the cosmetic active substance(s) may be from 0.001% to 20% by weight, preferably from 0.01% to 15% by weight, and more preferably from 0.1% to 10% by weight, relative to the total weight of the composition.

[0019] The microneedle may have a height of between 10 and 300 micrometers, preferably between 30 and 200 micrometers, and more preferably between 50 and 100 micrometers.

[0020] The microneedle may have the shape of a pyramid.

[0021] The base of the microneedle may have a width of 10 to 150 micrometers, preferably from 15 to 100 micrometers, and more preferably from 20 to 50 micrometers.

[0022] The ratio (height of the pyramid) / (width of the base of the pyramid) of the microneedle may be greater than or equal to 1, preferably greater than or equal to 1.5, and more preferably greater than or equal to 2.0.

[0023] The microneedles can be made from inorganic materials, preferably metals or non-metals, and more preferably silicon.

[0024] The present invention also relates to a kit for cosmetically treating a keratinous substance, such as the skin and the lips, comprising:

[0025] - at least one composition comprising at least one cosmetic active substance;

[0026] - a sheet of microneedles, comprising

[0027] - a substrate sheet, and

[0028] - a plurality of microneedles on the substrate sheet

[0029] - so that the microneedles can penetrate the keratinous substance, with a linear movement on the keratinous substance to make at least one pass on the keratinous substance, when applied to the keratinous substance; and

[0030] - an instruction carrier including instructions which

[0031] - if the frequency of application of the microneedle sheet on the substance keratinous is 3 times a week, the number of passes of the microneedle sheet on the keratinous substance during each application is not 5,

[0032] and

[0033] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0034] The kit may further comprise a device for applying the sheet of microneedles to the keratinous substance so that the microneedles can penetrate the keratinous substance.

[0035] The device of the above kit may be capable of applying the microneedle sheet repeatedly.

[0036] The present invention also relates to a use of a microneedle sheet, comprising

[0037] - a substrate sheet, and

[0038] - a plurality of microneedles on the substrate sheet,

[0039] - so that the microneedles can penetrate a keratinous substance, such as skin and lips, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance, when applied to the keratinous substance,

[0040] - provided that

[0041] - if the frequency of application of the microneedle sheet on the substance keratinous is 3 times a week, the number of passes of the microneedle sheet on the keratinous substance during each application is not 5,

[0042] and

[0043] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week,

[0044] - in combination with

[0045] - at least one composition comprising at least one cosmetic active substance,

[0046] - in order to reduce the risk of pigmentation of the keratinous substance. Brief description of the drawings

[0047] [Fig.l] shows a schematic view of a microneedle device which is preferably used for the present invention.

[0048] [Fig.2] shows the pigmentation scores of the cosmetic treatments according to Examples 1 and 2 and Comparative Examples 1 to 4.

[0049] [Fig.3] shows the pigmentation scores of the cosmetic treatments according to Example 3 and Comparative Examples 5 to 7. Best mode for carrying out the invention

[0050] After careful research, the inventors discovered that it was possible to provide a cosmetic process that uses microneedles that can reduce the risk of pigmentation of a keratinous substance such as the skin and lips due to the use of microneedles.

[0051] Thus, one aspect of the present invention is a cosmetic process for a keratinous substance such as skin and lips, comprising the steps of:

[0052] - application, on the keratinous substance, of at least one composition comprising at least one cosmetic active substance; and

[0053] - application, on the keratinous substance, of a sheet of micro-needles comprising a substrate sheet and a plurality of microneedles on the substrate sheet such that the microneedles can penetrate the keratinous substance, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance,

[0054] in which

[0055] - the frequency of application of the microneedle sheet to the substance keratinous is 3 times or less per week, and

[0056] - the number of passes of the microneedle sheet over the keratinous substance during each application is 5 or less,

[0057] - provided that

[0058] - if the frequency of application of the microneedle sheet on the substance keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5,

[0059] and

[0060] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0061] According to the present invention, the risk of pigmentation due to the use of microneedles can be reduced. Thus, possible pigmentations after the use of microneedles can be avoided or eliminated by the present invention.

[0062] The cosmetic process according to the present invention can provide the above effects independently of a combined use of a composition including at least one cosmetic active substance such as a depigmenting or lightening agent. However, if the cosmetic process according to the present invention is combined with a composition comprising at least one cosmetic active substance, the risk of pigmentation can be further reduced.

[0063] According to the present invention, the microneedles can penetrate a keratinous substance such as the skin. Thus, the microneedles can pierce the surface of the keratinous substance to create holes or fine passages through which the cosmetic active substance can penetrate into the keratinous substance such as the skin. Thus, the cosmetic active substance can penetrate into the keratinous substance through the holes or fine passages so that it can pass through the stratum corneum and / or reach the bottom of the stratum corneum. Furthermore, the cosmetic active substance can pass through the stratum corneum to reach one of the lower layers of the epidermis, such as a granular layer, a spinous layer, and a basal layer. Therefore, the cosmetic active substance can be easily delivered into the keratinous substance. This can provide effective cosmetic effects such as depigmenting or lightening effects.

[0064] Furthermore, the cosmetic active substance that passes through the stratum corneum can diffuse quite easily onto or into the epidermis to distribute itself uniformly in the keratinous substance. This therefore makes it possible to obtain uniform cosmetic effects.

[0065] Since microneedles do not cause pain, the cosmetic process according to the present invention can provide pain-free cosmetic treatments.

[0066] Furthermore, the cosmetic process according to the present invention can be carried out in a relatively short time.

[0067] Thus, the present invention is suitable for cosmetic or non-therapeutic treatments.

[0068] Hereinafter, the cosmetic process, kit and the like according to the present invention will be described in detail. [Cosmetic process]

[0069] The cosmetic process according to the present invention for a keratinous substance such as skin and lips comprises the steps of:

[0070] - application, on the keratinous substance, of at least one composition comprising at least one cosmetic active substance; and

[0071] - application, on the keratinous substance, of a sheet of micro-needles comprising a substrate sheet and a plurality of microneedles on the substrate sheet such that the microneedles can penetrate the keratinous substance, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance,

[0072] in which

[0073] - the frequency of application of the microneedle sheet to the substance keratinous is 3 times or less per week, and

[0074] - the number of passes of the microneedle sheet over the keratinous substance during each application is 5 or less,

[0075] - provided that

[0076] - if the frequency of application of the microneedle sheet on the substance keratinous is 3 times a week, the number of passes of the microneedle sheet on the keratinous substance during each application is not 5,

[0077] and

[0078] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0079] The cosmetic process according to the present invention may be intended for cosmetic treatments of a keratinous substance such as the skin and the lips, preferably the skin, and more preferably the skin of the face.

[0080] The cosmetic process according to the present invention can be used to improve the aesthetic appearance of a keratinous substance, for example, by depigmenting or lightening the keratinous substance.

[0081] The cosmetic process according to the present invention can reduce the risk of pigmentation of a keratinous substance. Therefore, for example, when microneedles are used to cosmetically treat hyperpigmentation of the skin, such as melasma, dark circles and brown spots, the cosmetic treatments can be safe, due to the reduced risk of re-pigmentation using the microneedles.

[0082] Hereinafter, the microneedle sheet and the like used for the cosmetic process according to the present invention, as well as examples of carrying out the cosmetic process according to the present invention, will be explained in detail. {Composition}

[0083] The cosmetic process according to the present invention comprises the step of applying, to a keratinous substance such as the skin and the lips, at least one composition comprising at least one cosmetic active substance.

[0084] The step of applying, to a keratinous substance, at least one composition comprising at least one cosmetic active substance can be carried out using any applicator such as a brush.

[0085] It may be preferable that the composition including at least one cosmetic active substance is applied to the keratinous substance in combination with at least one porous sheet such as a woven or non-woven fabric, in order to obtain good contact of the composition with the keratinous substance and good cosmetic effects on the desired site of the keratinous substance.

[0086] A porous sheet can absorb and maintain the composition comprising at least one cosmetic active substance. Therefore, the application of a porous sheet can facilitate the contact of the composition with the keratinous substance, which can contribute to good cosmetic effects on the keratinous substance.

[0087] The type of the above combination is not limited. Thus, a porous sheet can be applied to the keratinous substance after applying the composition to the keratinous substance. It is also possible to apply a porous sheet to the keratinous substance after applying the composition to the keratinous substance.

[0088] The step of applying, to a keratinous substance such as the skin and the lips, at least one composition comprising at least one cosmetic active substance can be carried out before or after the step of applying the sheet of micro-needles to the keratinous substance.

[0089] It is preferable that the step of applying, to a keratinous substance such as the skin and the lips, at least one composition comprising at least one cosmetic active substance is carried out before or after the step of applying the microneedle sheet to the keratinous substance. In other words, it is preferable that the composition is used as a pretreatment composition for a keratinous substance.

[0090] If the composition is used as a pretreatment composition, it may be preferable that the microneedle sheet be applied to the keratinous substance without a step of drying the composition on the keratinous substance. In other words, it may be preferable that the microneedle sheet be applied to the keratinous substance so that the microneedles can penetrate the keratinous substance before the composition dries or when the keratinous substance is wet.

[0091] If the cosmetic process according to the present invention further comprises the step of removing the microneedles from the surface of the keratinous substance, after the step of removing the microneedles from the surface of the keratinous substance, the composition comprising at least one cosmetic active substance can be removed from the surface of the keratinous substance.

[0092] However, it is preferable that the cosmetic process according to the present invention further comprises the step of maintaining or resting the composition comprising at least one cosmetic active substance on the keratinous substance after the step of removing the microneedles from the surface of the keratinous substance and before the step of removing the composition from the surface of the keratinous substance, since the composition can effectively penetrate into the keratinous substance via the holes formed on and in the keratinous substance by the microneedles.

[0093] The cosmetic active substance in the composition to be used for the cosmetic process according to the present invention may be chosen from skin care active substances.

[0094] Thus, it is preferable that the composition to be used for the cosmetic process according to the present invention is a cosmetic composition, and more preferably a cosmetic skin care composition.

[0095] (active skin care substance)

[0096] The composition to be used for the cosmetic process according to the present invention may comprise, as cosmetic active substance, at least one skin care active substance. If two or more skin care active substances are used, they may be the same or different.

[0097] The skin care active substance is herein intended to designate a substance for improving the aesthetic appearance and / or comfort of the skin. In particular, the skin care active substance may be intended to attenuate visible irregularities (dyschromia, hyperpigmentation, etc.) and / or tactile irregularities (wrinkles, subcutaneous fat, comedones, acne scars, etc.) of the skin, and / or to make the skin healthier, less oily and / or less dry.

[0098] The skin care active substance is not intended herein to mean a substance intended to impart a chromatic color to the skin. Thus, the skin care active substance does not include any pigment or colorant.

[0099] It may be preferable that the skin care active substance has a log P value ranging from -4.5 to 4.5, preferably from -4.0 to 4.0, and more preferably from -3.5 to 3.5.

[0100] A log P value is a value of the base ten logarithm of the apparent octan-l-ol / water partition coefficient. Log p values ​​are known and are determined by a standard test that determines the concentration of the compound in octan-l-ol and water. Log P can be calculated according to the method described in the article by Meylan and Howard: Atom / Fragment contribution method for estimating octanol-water partition coefficients, J. Pharm. Sci., 84: 83-92, 1995. This value can also be calculated using many commercially available software packages that determine log P based on the structure of a molecule. An example is the U.S. Environmental Protection Agency's Epiwin software.

[0101] The values ​​can be calculated using the ACD (Advanced Chemistry Development) Solaris V4.67 software; they can also be obtained from Exploring QSAR: hydrophobicity, electronic and steric constants (ACS professional reference work, 1995). There is also a website that provides estimated values ​​(address: http: / / esc.syrres.com / interkow / kowd emo.htm).

[0102] The skin care active ingredient may be in the form of a salt. Salts of the skin care active ingredient include conventional non-toxic salts of said compounds, such as those formed from an acid or a base.

[0103] It is preferable that the skin care active substance is a depigmenting or lightening agent, or an anti-aging agent such as an anti-wrinkle agent.

[0104] Depigmenting or lightening agent herein refers to any substance that can lighten the color of the skin or enhance the radiance of the skin surface.

[0105] As a depigmenting or lightening agent, vitamin B3 and its derivatives can be mentioned.

[0106] Vitamin B3, also called vitamin PP, is a compound with the following formula:

[0107] wherein R may be -CONH2 (niacinamide), -COOH (nicotinic acid or niacin), or CH2OH (nicotinic alcohol), -CO-NH-CH2-COOH (nicotinuric acid), or -CO-NH-OH (niconityl hydroxamic acid). Niacinamide is preferred.

[0108] Vitamin B3 derivatives that may be mentioned include, for example, nicotinic acid esters such as tocopherol nicotinate, amides derived from niacinamide by substitution of the hydrogen groups of -CONH2, reaction products with carboxylic acids and amino acids, esters of nicotinyl alcohol and carboxylic acids such as acetic acid, salicylic acid, glycolic acid or palmitic acid.

[0109] The following derivatives may also be mentioned: 2-chloronicotinamide, 6-methylnicotinamide, 6-aminonicotinamide, N-methylnicotinamide, N,N-dimethylnicotinamide, N-(hydroxymethyl)nicotinamide, quinolinic acid imide, nicotinanilide, N-benzylnicotinamide, N-ethylnicotinamide, nifenazone, nicotinaldehyde, isonicotinic acid, methylisonicotinic acid, thionicotinamide, nialamide, 2-mercaptonicotinic acid, nicomol and niaprazine, methyl nicotinate and sodium nicotinate.

[0110] Other vitamin B3 derivatives which may also be cited include its inorganic salts, such as chlorides, bromides, iodides or carbonates, and its organic salts, such as salts obtained by reaction with carboxylic acids, such as acetate, salicylate, glycolate, lactate, malate, citrate, mandelate, tartrate, etc.

[0111] Ascorbic acid and its derivatives may be mentioned as a depigmenting or lightening agent.

[0112] Ascorbic acid is generally in L-form, since it is usually extracted from natural products.

[0113] Due to its chemical structure (α-keto lactone) which makes it very sensitive to certain environmental parameters such as light, heat and aqueous media, it may be advantageous to use ascorbic acid in the form of a derivative or analogue chosen, for example, from ascorbic acid saccharide esters or phosphoryl ascorbic acid metal salts, alkali metal salts, esters and sugars.

[0114] The saccharide esters of ascorbic acid which can be used in the present invention are in particular the glycosyl, mannosyl, fructosyl, fucosyl, galactosyl, N-acetylucosamine and N-acetylmuramic derivatives of ascorbic acid, and mixtures thereof, and more particularly ascorbyl glucoside such as ascorbyl-2 glucoside, 2-OaD-glucopyranosyl L-ascorbic acid or 6-O-[3-D-galactopyranosyl L-ascorbic acid. These latter compounds and the processes for their preparation are described in particular in documents EP-A-0 487 404, EP-A-0 425 066 and JP 05 213 736.

[0115] As regards the metal salt of phosphoryl ascorbic acid, it may be chosen from alkali metals and in particular sodium, ascorbyl phosphates, alkaline earth metal ascorbyl phosphates and transition metal ascorbyl phosphates.

[0116] It is also possible to use ascorbic acid precursors such as active agent amides and active agent saccharide derivatives, which involve proteases or peptidases and glycosidases as enzymes, respectively. to release ascorbic acid in situ. These compounds are described in patent EP 0 667 145.

[0117] The active agent saccharide derivatives are particularly selected from C3 to C6 saccharide derivatives. They are particularly selected from glucosyl, mannosyl, fructosyl, fucosyl, N-acetylglucosamine, galactosyl and N-acetylgalactosamine derivatives, N-acetylmuramic acid derivatives and sialic acid derivatives, and mixtures thereof.

[0118] The second ascorbic acid precursors may be selected from derivatives which are hydrolyzed by other enzymes, for example by esterases, phosphatases, sulfatases, etc. According to the present invention, the second active agent precursors may be selected, for example, from phosphates; sulfates; palmitates; acetates; propionates; ferulates and, in general, alkyl or acyl esters; alkyl or acyl ethers of active agent. The acyl and alkyl radicals contain in particular from 1 to 30 carbon atoms. As a skin care active substance, mention may be made of 3-O-ethyl ascorbic acid.

[0119] In particular, the second precursor may be an ester derived from the reaction with a mineral acid such as a sulfate or a phosphate to react with a sulfatase or a phosphatase upon contact with the skin, and the second precursor may be an acyl or alkyl ester derived from the reaction with an organic acid, for example a palmitic acid, an acetic acid, a propionic acid, a nicotinic acid, a 1,2,3-propanetricarboxylic acid or a ferulic acid to react with a specific skin esterase.

[0120] Other derivatives are described, for example, in patent EP 1 430 883.

[0121] Analogues of ascorbic acid are more particularly its salts, in particular alkali metal salts, for example sodium ascorbate, its esters, in particular its acetic, propionic or palmitic esters, or its sugars, in particular glycosyl ascorbic acid.

[0122] As a depigmenting or lightening agent, mention may be made of resorcinol derivatives.

[0123] The resorcinol derivative may preferably be derivatives substituted at the 4-position, such as 4-alkylresorcinols, more preferably phenylethyl resorcinol, 4-n-butylresorcinol and 4-(tetrahydro-2H-pyran-4-yl)benzene-1,3-diol, and in particular phenylethyl resorcinol due to its lightening effect. Phenylethyl resorcinol is also called 4-(l-phenylethyl)-1,3-benzenediol and is represented by the following chemical formula. Phenylethyl resorcinol can be obtained, for example, from Symrise Corp (product name: Symwhite 377®). HQ v OH

[0124] As other examples of resorcinol derivatives, mention may be made of: 2-methylresorcinol, 5-methylresorcinol, 4-methylresorcinol, 4-ethylresorcinol, 2,5-dimethylresorcinol, 4,5-dimethylresorcinol, 2,4-dimethyl-1,3-benzenediol, 3,5-dihydroxybenzylamine, 5-methoxyresorcinol, 3,5-dihydroxybenzyl alcohol, 2-methoxyresorcinol, 4-methoxyresorcinol, 3,5-dihydroxytoluene monohydrate, 4-chlororesorcinol, 2-chlororesorcinol, 2',4'-dihydroxyacetophenone, 3',5'-dihydroxyacetophenone, 2,6-dihydroxy-4-methylbenzaldehyde, 4-propylresorcinol, 2,4-dihydroxy-1,3,5-trimethylbenzene, 3,5-dihydroxybenzamide, 2,6-dihydroxybenzamide, 2,4-dihydroxybenzamid e, 2,4-dihydroxybenzoic acid, 2,6-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 2,6-dihydroxy-4-methylbenzyl alcohol, 3,5-dihydroxyanisole hydrate, 4-aminoresorcinol hydrochloride, 2-aminoresorcinol hydrochloride,5-aminobenzene-1,3-diol hydrochloride, 2',4'-dihydroxypropiophenone, 2',4'-dihydroxy-3'-methylacetophenone, (2,4-dihydroxyphenyl)acetone, (3,5-dihydroxyphenyl)acetone, 2,6-dihydroxy-4'-methylacetophenone, 4-n-butylresorcinol, 2,4-diethyl-1,3-benzenediol, 3,5-dihydroxy-4-methylbenzoic acid, 2,6-dihydroxy-4-methylbenzoic acid, 2,4-dihydroxy-6-methylbenzoic acid, 3,5-dihydroxyphenylacetic acid, 2-ethyl-5-methoxybenzene-1,3-diol, 4-amino-3,5-dihydroxybenzoic acid, monohydrate 3,5-dihydroxyacetophenone, 3,5-dihydroxybenzylamine hydrochloride, 4,6-dichlororesorcinol, 2',4'-dihydroxy-3'-methylpropiophenone, 1-(3-ethyl-2,6-dihydroxyphenyl)ethan-1-one, 2',6'-dihydroxy-4'-methoxyacetophenone, 1-(2,6-dihydroxy-3-methoxyphenyl)ethan-1-one, 3(2,4-dihydroxyphenylpropionic acid and 2,4-dihydroxy-3,6-dimethylbenzoic acid. ,

[0125] As a depigmenting or lightening agent, tranexamic acid and its derivatives may also be mentioned.

[0126] Examples of tranexamic acid derivatives include tranexamic acid dimers (such as trans-4-(trans-aminomethylcyclohexanecarbonyl)aminomethylcyclohexanecarboxylic acid hydrochloric acid), tranexamic acid esters of hydroquinone (such as 4'-hydroxyphenyl trans-4-aminomethylcyclohexanecarboxylate), tranexamic acid esters of gentisic acid (such as 2-(trans-4-aminomethylcyclohexanecarbonyloxy)-5-hydroxybenzoic acid and its salts), tranexamic amides (such as trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salts, and trans-4-(p-methoxybenzoyl)aminomethylcyclohexanecarboxylic acid and its salts, and trans-4-guanidinomethylcyclohexanecarboxylic acid and its salts), and the like.

[0127] It is preferable that the depigmenting or lightening agent is selected from the group consisting of niacinamide, phenylethyl resorcinol, tranexamic acid and a mixture thereof.

[0128] As an anti-aging agent, hyaluronic acid substances can be mentioned.

[0129] The hyaluronic acid substance may be selected from the group consisting of hyaluronic acid, hyaluronic acid salts, hyaluronic acid derivatives, salts of hyaluronic acid derivatives and mixtures thereof.

[0130] Hyaluronic acid is a predominant glucosaminoglycan found in the skin. Thus, fibroblasts mainly synthesize collagens, matrix glycoproteins other than collagens (fibronectin, laminin), proteoglycans and elastin. Keratinocytes, on the other hand, mainly synthesize sulfated glycosaminoglycans and hyaluronic acid. Hyaluronic acid is also called hyaluronan.

[0131] Hyaluronic acid is present in the free state in the epidermis and dermis and is responsible for the turgor of the skin. This polysaccharide can in fact retain a large volume of water, corresponding to 1,000 times its weight. In this sense, hyaluronic acid plays an important role in increasing the amounts of bound water in tissues, as well as in the mechanical properties of the skin and in the formation of wrinkles.

[0132] Hyaluronic acid can be represented by the following chemical formula.

[0134] In the context of the present invention, the expression "hyaluronic acid" covers in particular the basic unit of hyaluronic acid of formula:

[0135] This is the smallest fraction of hyaluronic acid comprising a disaccharide dimer, namely D-glucuronic acid and N-acetylglucosamine.

[0136] The hyaluronic acid derivatives may be selected from the group consisting of hydrolyzed hyaluronic acid, acetylated hyaluronic acid, cationic hyaluronic acid and mixtures thereof.

[0137] The cationic hyaluronic acid comprises at least one cationic moiety. The cationic moiety may be a trialkyl ammonium group such as -N+(CH3)3. The cationic moiety may include at least one hydroxyl group. Examples of the cationic group include -CH2-CH(OH)-CH2-N+(CH3)3.

[0138] Examples of cationic hyaluronic acid include hydroxypropyltrimonium hyaluronate.

[0139] As hyaluronic acid salts or salts of hyaluronic acid derivatives, mention may be made of alkali metal salts such as the sodium salt and the potassium salt, alkaline earth metal salts such as magnesium salts, ammonium salts and mixtures thereof.

[0140] The molecular weight of the hyaluronic acid substance is not limited. The molecular weight of the hyaluronic acid substance may be greater than or equal to 5 kDa, preferably greater than or equal to 20 kDa, and more preferably greater than or equal to 100 kDa. The molecular weight of the hyaluronic acid substance may be less than or equal to 20 MDa, preferably less than or equal to 10 MDa, and more preferably less than or equal to 2,000 kDa. Thus, the molecular weight of the hyaluronic acid substance may be from 5 kDa to 20 MDa, preferably from 20 kDa to 10 MDa, and more preferably from 100 kDa to 2,000 kDa.

[0141] Unless otherwise indicated in the descriptions, "molecular weight" means a number average molecular mass.

[0142] The hyaluronic acid substance may in particular be hyaluronic acid supplied by the company Hyactive under the trade name CPN (MW: 10 to 150 kDa), by the company Soliance under the trade name Cristalhyal (MW: 1 to 1.4 MDa), by the company Bioland under the name Nutra HA (MW: 820,000 Da), by the company Bioland under the name Nutra AF (MW: 69,000 Da), or by the company Bioland under the name Oligo HA (MW: 6,100 Da).

[0143] A single hyaluronic acid substance of a single molecular weight, or a combination of two or more hyaluronic acid substances of different molecular weights, may be used.

[0144] In one embodiment of the present invention, the cosmetic active substance may be selected from skin care active substances, preferably from the group consisting of depigmenting or lightening agents, anti-aging agents and mixtures thereof, and more preferably selected from the group consisting of vitamin B3 and its derivatives, ascorbic acid and its derivatives, resorcinol derivatives, tranexamic acid and its derivatives, hyaluronic acid substances and mixtures thereof.

[0145] In another embodiment of the present invention, the cosmetic active substance may be chosen from depigmenting or lightening agents, and preferably from the group consisting of niacinamide, phenylethyl resorcinol, tranexamic acid and a mixture thereof.

[0146] (Quantity of cosmetic active substance)

[0147] The amount of the cosmetic active substance(s) in the composition used for the cosmetic process according to the present invention is not limited.

[0148] The quantity of the cosmetic active substance(s) in the composition to be used for the cosmetic process according to the present invention may be greater than or equal to 0.001% by weight, preferably greater than or equal to 0.01% by weight, and more preferably greater than or equal to 0.1% by weight, relative to the total weight of the composition.

[0149] The quantity of the cosmetic active substance(s) in the composition to be used for the process according to the present invention may be less than or equal to 20% by weight, preferably less than or equal to 15% by weight, and more preferably less than or equal to 10% by weight, relative to the total weight of the composition.

[0150] Thus, the quantity of the cosmetic active substance(s) in the composition to be used for the cosmetic process according to the present invention may range from 0.001% to 20% by weight, preferably from 0.01% to 15% by weight, and more preferably from 0.1% to 10% by weight, relative to the total weight of the composition.

[0151] (Vehicle)

[0152] The composition to be used for the cosmetic process according to the present invention may comprise at least one vehicle.

[0153] The vehicle in the composition to be used for the cosmetic process according to the present invention is not limited.

[0154] For example, the vehicle may be selected from hydrophilic media and hydrophobic media.

[0155] The hydrophilic media may be alcohols: in particular monovalent alcohols such as ethyl alcohol, isopropyl alcohol, benzyl alcohol and phenylethyl alcohol; diols such as ethylene glycol, propylene glycol and butylene glycol; other polyols such as glycerol, sugar and carbohydrate alcohols; and ethers such as ethylene glycol monomethyl, monoethyl and monobutyl ethers, propylene glycol monomethyl, monoethyl and monobutyl ethers, and butylene glycol monomethyl, monoethyl and monobutyl ethers.

[0156] The hydrophobic media can be chosen from oils.

[0157] It may be preferable that the composition to be used for the cosmetic process according to the present invention comprises water.

[0158] The amount of the vehicle(s) in the composition to be used for the present invention may be greater than or equal to 50% by weight, preferably greater than or equal to 55% by weight, and more preferably greater than or equal to 60% by weight, relative to the total weight of the composition.

[0159] The amount of the vehicle(s) in the composition to be used for the present invention may be less than or equal to 99% by weight, preferably less than or equal to 95% by weight, and more preferably less than or equal to 90% by weight, relative to the total weight of the composition.

[0160] The amount of the vehicle(s) in the composition to be used for the present invention may be from 50% to 99% by weight, preferably from 55% to 95% by weight, and more preferably from 60% to 90% by weight, relative to the total weight of the composition.

[0161] (Optional substances)

[0162] The composition to be used for the cosmetic process according to the present invention may comprise, in addition to the above-mentioned substances, additives generally used in cosmetics, more precisely, surfactants or emulsifiers, hydrophilic or lipophilic thickeners, natural extracts derived from animals or plants, waxes and the like, within a range which does not affect the effects of the present invention.

[0163] The composition to be used for the cosmetic process according to the present invention may comprise the above optional additive(s) in an amount of 0.01% to 50% by weight, preferably 0.05% to 30% by weight, and more preferably 0.1% to 10% by weight, relative to the total weight of the composition.

[0164] (Preparation)

[0165] The composition to be used for the present invention may be prepared, for example, by mixing one or more cosmetic active substances such as one or more depigmenting or lightening agents, and one or more carriers, as essential substances, and one or more optional substances, if necessary, as explained above.

[0166] The method and means for mixing the above essential and optional substances are not limited. Any conventional method and means can be used for mixing the above essential and optional substances to prepare the composition to be used for the present invention. {Microneedle Sheet}

[0167] The cosmetic process according to the present invention comprises the step of applying, to a keratinous substance, such as the skin and the lips, a sheet of microneedles.

[0168] The microneedle sheet to be used for the cosmetic process according to the present invention comprises a substrate sheet and a plurality of microneedles on the substrate sheet.

[0169] The microneedle sheet to be used for the present invention can be considered as a cosmetic device, preferably a cosmetic device for a keratinous substance, and more preferably a cosmetic device for the skin, in particular the skin of the face, as well as the lips.

[0170] According to the cosmetic process according to the present invention, a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet is applied to a keratinous substance, such as skin and lips, so that the microneedles can penetrate the keratinous substance, with a linear movement on the keratinous substance in order to make at least one pass on the keratinous substance.

[0171] It is preferable that the linear movement is performed for a desired area on the keratinous substance. For example, it is preferable that the application site of the microneedle sheet can move in a linear direction over a desired area of ​​the surface of the keratinous substance, provided that the microneedles can penetrate the desired area on the keratinous substance.

[0172] The cosmetic process according to the present invention may further comprise the step of removing the microneedles from the surface of the keratinous substance.

[0173] (Micro-needles)

[0174] The microneedle sheet to be used for the present invention comprises a plurality of microneedles.

[0175] The microneedles are present on the surface of a substrate sheet. The microneedles may be present on 50% or more, preferably 70% or more, and more preferably 90% or more of the surface area of ​​the substrate sheet.

[0176] It is preferable that the microneedles are present on one of the surfaces of a substrate sheet.

[0177] It is preferable that the microneedles of the microneedle sheet to be used for the present invention are designed to penetrate or enter the stratum corneum of the skin, particularly the skin of the face, as well as the lips.

[0178] A microneedle may be of any size and shape suitable for puncturing the stratum corneum. It may be preferable for the microneedles to be designed to pierce and penetrate the stratum corneum. The microneedles may create openings or passages in the stratum corneum.

[0179] If necessary, the height of the microneedles can be adjusted so as to allow penetration of the epidermis and / or the dermis of the skin, preferably the epidermis, and more preferably one of the layers of the epidermis.

[0180] The shape of the microneedles is not limited as long as the shape is a "needle." It will be apparent to those skilled in the art that the microneedles for the present invention may take any reasonable shape, including, but not limited to, pyramids, cones, rods, and / or pillars. As such, the microneedles may have the same diameter at the tip as at the base or may be tapered in the direction from the base to the tip.

[0181] For example, the shape of the microneedle may be a triangular pyramid, a square pyramid, or a pentagonal pyramid. Alternatively, the microneedle may be in the shape of a cylinder, preferably with a tip that may be formed by cutting the cylinder diagonally. The cross-section of the microneedle may take any geometric shape, including circular, triangular, square, rectangular, polyhedral, regular or irregular, and the like. In one embodiment, a group of microneedles may take the form of hollow microcapillaries. However, for the present invention, solid (non-hollow) microneedles may be preferable.

[0182] Reference is therefore made to "microneedles" as the type of microprotrusion or microprotrusion employed. It will be understood by those skilled in the art that in many instances the same inventive principles apply to the use of other microprotrusions or microprotrusions to penetrate the skin. Other microprotrusions or microprotrusions may include, for example, microblades as described in U.S. Patent No. 6,219,574 and Canadian Patent Application No. 2,226,718 and sharp microneedles as described in U.S. Patent No. 6,652,478.

[0183] The height or length of the microneedle of the microneedle sheet to be used for the present invention may be 10 to 300 micrometers, preferably 30 to 200 micrometers, and more preferably 50 to 100 micrometers.

[0184] According to one embodiment of the present invention, the microneedle is in the form of a cone.

[0185] The cone may include a distal end such as a tip and a base. The base may be a circle or an oval.

[0186] The height or length of the microneedle cone of the microneedle sheet to be used for the present invention may be 10 to 300 micrometers, preferably 30 to 200 micrometers, and more preferably 50 to 100 micrometers.

[0187] The base of the microneedle cone of the microneedle sheet to be used for the present invention may have a diameter or width of 10 to 150 micrometers, preferably 15 to 100 micrometers, and more preferably 20 to 50 micrometers. If the base of the microneedle cone of the microneedle sheet to be used for the present invention is oval or elliptical in shape, the major axis length or width of the oval may be 10 to 150 micrometers, preferably 15 to 100 micrometers, and more preferably 20 to 50 micrometers.

[0188] The microneedle may have an aspect ratio (length / width at the base) of at least about 3:1, at least about 2:1, or at least about 1:1. The (cone height) / (cone base diameter) ratio of the microneedle may be greater than or equal to 1, preferably greater than or equal to 1.5, and more preferably greater than or equal to 2.0.

[0189] According to another embodiment of the present invention, the microneedle is pyramid-shaped, such as a triangular pyramid and a square pyramid.

[0190] The pyramid may include a distal end such as a tip and a base. The shape of the base may be a triangle or a square.

[0191] The height or length of the microneedle pyramid of the microneedle sheet to be used for the present invention may be 10 to 300 micrometers, preferably 30 to 200 micrometers, and more preferably 50 to 100 micrometers.

[0192] The base of the microneedle pyramid of the microneedle sheet to be used for the present invention may have a width or side of 10 to 150 micrometers, preferably 15 to 100 micrometers, and more preferably 10 to 50 micrometers. If the base of the microneedle pyramid of the microneedle sheet to be used for the present invention is in the shape of a triangle or a square, the length of the width or side of the triangle or square may be 10 to 150 micrometers, preferably 15 to 100 micrometers, and more preferably 20 to 50 micrometers.

[0193] The microneedle may have an aspect ratio (length / width at the base) of at least about 3:1, at least about 2:1, or at least about 1:1. The ratio (height of the pyramid) / (width of the base of the pyramid) of the microneedle may be greater than or equal to 1, preferably greater than or equal to 1.5, and more preferably greater than or equal to 2.0.

[0194] It may be preferable that the microneedle is capable of penetrating a keratinous substance, such as skin and lips, to a depth of less than or equal to 200 micrometers, preferably less than or equal to 180 micrometers, and more preferably less than or equal to 160 micrometers.

[0195] A very narrow pitch of microneedles may not provide the microneedles with sufficient surface area so that the microneedles do not penetrate the skin. On the other hand, too wide a pitch may also result in a problem that the individual microneedle may not have sufficient pressure for penetration. Thus, it may be preferable for a pitch of microneedle arrays to be 400 to 700 micrometers, and more preferably 400 to 500 micrometers.

[0196] The number of microneedles and the pitch between the microneedles depends on certain factors such as the desired color pattern and the width of a microneedle. For example, if a color pattern with a width of 0.5 micrometers is desired, the use of a microneedle sheet having a microneedle array (2x2) with a pitch of 0.5 mm may be most suitable.

[0197] In one embodiment, the density of the microneedles may be 100 to 2,000 microneedles / cm2, preferably 200 to 1,000 microneedles / cm2, and even more preferably 200 to 500 microneedles / cm2.

[0198] It is preferable that the microneedles are not soluble.

[0199] "Non-dissolving" microneedle means that the microneedle cannot break down or disintegrate within a keratinous substance such as skin and lips for example by a natural moisturizing factor or external moisture.

[0200] It is more preferable that the microneedles are not water-soluble.

[0201] The microneedles may be made of organic or inorganic materials. Examples of organic materials include synthetic polymers, including polyethylene, polypropylene and photosensitive resins, biodegradable plastics, cellulose derivatives and mixtures thereof. Examples of inorganic materials include metals, including stainless steel, non-metals such as silicon, glass and ceramics, and mixtures thereof. Any other material that can be implanted in the skin or body may also be used.

[0202] It is preferable that the microneedles are sterile or sterilized before use. It is preferable that the microneedles are used only once and are therefore disposable.

[0203] It is preferable that the microneedles are composed of inorganic materials, more preferably of metals or non-metals, and even more preferably of silicon (in particular, monocrystalline silicon).

[0204] It is also preferable that the microneedles are solid (not hollow).

[0205] (Substrate sheet)

[0206] The microneedle sheet to be used for the present invention comprises a substrate sheet on which the microneedles are present or placed.

[0207] The substrate sheet and the microneedles may be separate or integrated.

[0208] For example, the substrate sheet and the microneedles may comprise at least one common material. Thus, in one embodiment, the substrate sheet and the microneedles may be a single element comprising at least one common material. Preferably, the single element may be prepared using the same material.

[0209] On the other hand, the substrate sheet may be different or distinct from the microneedles. For example, the substrate sheet and the microneedles may be made of different materials. In this case, the substrate sheet may be chosen, for example, from masks, wipes, patches and, in general, all types of porous substrate sheets. Preferably, these substrate sheets have an oblong structure, i.e. a thickness less than the dimensions of the plane in which they are defined.

[0210] The substrate sheet may be cut into the shape of a patch, disc, mask, towel, glove, pre-cut roll, or any other shape suitable for cosmetic use.

[0211] (Preparation)

[0212] There is no limitation as to how to prepare the microneedle sheet to be used for the cosmetic process according to the present invention. It is possible to prepare the microneedle sheet to be used for the cosmetic process according to the present invention on the basis of conventional technology such as molding, 3D printing, metal processing, and the like.

[0213] The shape of the microneedle sheet to be used for the cosmetic process according to the present invention is not limited and may be any shape such as the shape of lips or a shape suitable for application under the eyes, depending on the application target of the microneedle sheet. {Device}

[0214] In the cosmetic process according to the present invention, the microneedle sheet is applied to a keratinous substance, such as skin and lips, so that the microneedles can penetrate the keratinous substance.

[0215] It is preferable that the microneedles can penetrate the keratinous substrate repeatedly.

[0216] The manner of performing repeated penetrations of microneedles into a keratinous substance is not limited. For example, the repeated penetrations can be performed by repeatedly tapping with fingers on the back surface of the substrate sheet of the microneedle sheet so that the microneedles on the front surface of the substrate sheet can repeatedly penetrate the keratinous substance.

[0217] Furthermore, it is preferable to carry out the repeated penetrations of the microneedles using vibrations towards a keratinous substance such as the skin and lips.

[0218] For example, as shown in [Fig.l], a microneedle sheet 1 may be connected to an oscillator 2 that can produce vibrations toward the surface of a keratinous substance, which corresponds to the up and down direction in [Fig.l]. The type of the oscillator 2 is not limited as long as it can produce vibrations. For example, the oscillator 2 may be made of a piezoelectric element. Of course, any other actuator that can repeatedly move, preferably vibrate, toward a keratinous substance may be used instead of the oscillator 2.

[0219] In [Fig.l], the microneedle sheet 1 can move up and down according to the vibrations caused by the oscillator 2, and thus the microneedles on the microneedle sheet 1 can repeatedly penetrate a keratinous substance such as skin and lips.

[0220] It is preferable that the oscillator 2 is connected to a head which can serve as a receiver for the microneedle sheet 1, and that the substrate sheet of the microneedle sheet 1 is fixed to the head. Thus, the vibrations caused by the oscillator 2 can be transmitted to the head. The microneedle sheet 1 can then also vibrate via the head.

[0221] It is preferable to use a device to vibrate the microneedle sheet 1. For example, the device may comprise the oscillator 2 and the head which is connected to the oscillator 2, as well as a battery, such as a dry cell, which can drive the oscillator 2 and a control means for controlling the frequency of the vibrations caused by the oscillator 2. As an example, a device disclosed in WO 2011 / 115602, the contents of which are incorporated herein by reference, may be used as the above device.

[0222] When using the above device, the microneedle sheet 1 can be mounted on the head of the device and can be applied to a keratinous substance such as skin and lips so that the microneedles of the microneedle sheet 1 can repeatedly penetrate the keratinous substance.

[0223] The vibration or tapping frequency is not limited. For example, the frequency may be from 1,000 to 10,000 per minute, preferably from 1,000 to 8,000 per minute, and more preferably from 3,000 to 6,000 per minute.

[0224] It may be preferable to regulate the pressure to be used to penetrate the microneedles into a keratinous substance. The pressure may depend on certain factors such as the type of microneedles.

[0225] Tapping or vibrating penetration of the microneedles allows for continuous and stable skin puncture and can reduce the force required to drive the microneedle into the keratinous substance. It can further provide massaging effects on the treated area of ​​the keratinous substance.

[0226] {How to carry out the cosmetic process}

[0227] According to the cosmetic process according to the present invention, a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet is applied to a keratinous substance, such as skin, such that the microneedles can penetrate the keratinous substance, with a linear movement on the keratinous substance in order to make at least one pass on the keratinous substance.

[0228] According to the present invention, the above application satisfies the following conditions:

[0229] - the frequency of application of the microneedle sheet on the substance keratinous is 3 times or less per week, and

[0230] - the number of passes of the microneedle sheet over the keratinous substance during each application is 5 or less,

[0231] - provided that

[0232] - if the frequency of application of the microneedle sheet on the substance keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5,

[0233] and

[0234] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0235] Regulating the frequency of application and the number of passes at each application in the cosmetic process according to the present invention can reduce the risk of pigmentation due to the use of microneedles.

[0236] Thus, for example, if the frequency of application of the micro-needle sheet to the keratinous substance is 3 times per week, the number of passes of the micro-needle sheet over the keratinous substance during each application may be less than or equal to 4, preferably less than or equal to 3, and more preferably less than or equal to 2.

[0237] On the other hand, for example, if the number of passes of the microneedle sheet over the keratinous substance during each application is 5, the frequency of application of the microneedle sheet over the keratinous substance may be 2 times per week, and preferably 1 time per week.

[0238] It may be preferable that, in the cosmetic process according to the present invention,

[0239] the frequency of application of the microneedle sheet on the keratinous substance either 3 times a week, and

[0240] that the number of passes of the micro-needle sheet over the keratinous substance during each application is 2.

[0241] It may be preferable that, in the cosmetic process according to the present invention,

[0242] the frequency of application of the microneedle sheet on the keratinous substance either twice a week, and

[0243] that the number of passes of the micro-needle sheet over the keratinous substance during each application is 5. [Necessary and Use]

[0244] The present invention also relates to a kit for cosmetically treating a keratinous substance, such as the skin and the lips, comprising:

[0245] - at least one composition comprising at least one cosmetic active substance;

[0246] - a sheet of microneedles, comprising

[0247] - a substrate sheet, and

[0248] - a plurality of microneedles on the substrate sheet

[0249] - so that the microneedles can penetrate the keratinous substance, with a linear movement on the keratinous substance to make at least one pass on the keratinous substance, when applied to the keratinous substance; and

[0250] - an instruction carrier including instructions that

[0251] - if the frequency of application of the microneedle sheet on the substance keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5,

[0252] and

[0253] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week.

[0254] The above support may be, for example, a sheet made from any material such as paper.

[0255] The above explanations for the composition and the microneedle sheet for the cosmetic process according to the present invention can also be applied to those of the kit according to the present invention.

[0256] The kit may further comprise a device for applying the sheet of microneedles to the keratinous substance so that the microneedles can penetrate the keratinous substance.

[0257] The above explanations for the device which can be used for the cosmetic process according to the present invention can also be applied to the device which can be used for the kit according to the present invention.

[0258] It is preferable that the device is capable of applying the microneedle sheet repeatedly. For example, the device may comprise at least one element capable of vibrating or tapping the microneedle sheet. This element may correspond to the back surface of the substrate sheet if tapping with the fingers is used to repeat the penetration of the microneedles into a keratinous substance, and to the oscillator 2 of [Fig.l] explained above if vibration is used to repeat the penetration of the microneedles into a keratinous substance.

[0259] The composition comprising at least one cosmetic active substance may be contained in any container such as a container commonly used for cosmetic purposes.

[0260] The kit may preferably be used to perform a cosmetic process according to the present invention.

[0261] The present invention also relates to a use of a microneedle sheet, comprising

[0262] - a substrate sheet, and

[0263] - a plurality of microneedles on the substrate sheet,

[0264] - so that the microneedles can penetrate a keratinous substance, such as skin and lips, with a linear movement of the microneedle sheet over the keratinous substance to make at least one pass of the microneedle sheet over the keratinous substance, when applied to the keratinous substance,

[0265] - provided that

[0266] - if the frequency of application of the microneedle sheet on the substance keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5,

[0267] and

[0268] - if the number of passes of the microneedle sheet over the substance keratinous substance during each application is 5, the frequency of application of the microneedle sheet on the keratinous substance is not 3 times per week,

[0269] - in combination with

[0270] - at least one composition comprising at least one cosmetic active substance,

[0271] - in order to reduce the risk of pigmentation of the keratinous substance.

[0272] The above explanations for the composition and the microneedle sheet for the cosmetic process according to the present invention can also be applied to those of the use according to the present invention.

[0273] More specifically, the use according to the present invention may comprise

[0274] the first application, on the keratinous substance, of at least one composition comprising at least one cosmetic active substance; and

[0275] the second application, on the keratinous substance, on which the composition has been applied, of a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet such that the microneedles are capable of penetrating into the keratinous substance, in order to reduce the risk of pigmentation of the keratinous substance.

[0276] It is preferable that the microneedles can penetrate the keratinous substrate repeatedly. The repetitions may be based on vibration or tapping of the microneedle sheet.

[0277] Another aspect of the use according to the present invention may be a composition comprising at least one cosmetic active substance, preferably at least one depigmenting or lightening agent, for use in reducing the risk of pigmentation, in combination with a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet, wherein the microneedles can penetrate into the keratinous substance.

[0278] According to the above kit and use according to the present invention, the microneedles of a microneedle sheet can deliver the cosmetic active ingredient to a keratinous substance such as skin and lips to provide the keratinous substance with cosmetic effects. If the cosmetic active ingredient is a depigmenting or lightening agent, the above kit and use according to the present invention can provide a keratinous substance such as skin with depigmenting or lightening effects. If the cosmetic active ingredient is an anti-aging agent, such as an anti-wrinkle agent, the above kit and use according to the present invention can provide a keratinous substance such as skin with anti-aging effects such as anti-wrinkle effects. EXAMPLES

[0279] The present invention will be described in more detail by way of examples. However, these examples should not be construed as limiting the scope of the present invention. The examples below are presented as non-limiting illustrations within the scope of the present invention. Examples 1 and 2 and comparative examples 1 to 4

[0280] (Microneedle device)

[0281] A square microneedle sheet (5 mmx5 mm square) with 7x7 microneedles on a substrate sheet was used. Each microneedle was in the shape of a pyramid with a length or height of 80 pm and a base width of 40 pm. The microneedles were made of single-crystal silicon.

[0282] The square microneedle sheet was mounted on a head (first end) of a device as shown in WO 2011 / 115602, in which the head can vibrate with the axis of the device, to prepare a microneedle device which can apply the microneedle sheet to the skin with a vibration action toward the skin so that the microneedles can repeatedly penetrate the skin.

[0283] (Composition)

[0284] The following composition A shown in Table 1 was prepared by mixing the ingredients shown in Table 1.

[0285] [Table l]Table 1 Composition A Weight (%) Glycerin 5 Sodium hyaluronate 1.5 Preservative qs PEG-60 hydrogenated castor oil 0.32 Water qs 100

[0286] (Evaluation)

[0287] First, for Examples 1 and 2 and Comparative Examples 1 to 4, a human cadaver skin with a shape of 1.5 cm x 1.5 cm square was provided as a skin sample.

[0288] Second, for Examples 1 and 2 and Comparative Examples 2 and 4, Composition A was applied to one site (1 cmxl cm square) on the above skin sample.

[0289] Third, for Examples 1 and 2 and Comparative Examples 3 and 4, the above skin sample was treated by the above microneedle device. Specifically, the above microneedle device was used to apply the microneedle sheet on the above site on the skin sample so that the microneedles repeatedly penetrate the above site on the skin sample, with vibration of a frequency of 5,000 times per minute, and linear movement such as 2 strokes every 8 seconds so as to cover the above site on the skin sample once (one pass).

[0290] Next, for Examples 1 and 2 and Comparative Examples 1 to 4, twelve skin sections (in the form of thin plates) were obtained by slicing the above skin sample. The twelve skin sections were stained by a modified Fontana-Masson stain to stain the melanin and argentaffin granules in the skin sections black / dark gray / brown. Then, the skin sections were analyzed by pigmentation analysis, as follows.

[0291] Pigmentation analysis: The amount of melanin present in each section was evaluated by estimating the intensity and distribution of the gray tint. Briefly, an 8-bit grayscale image was obtained by microscopic observation of the section. Then, the color space of the image was transformed from the RGB system to the L*a* b* system, and each pixel in each image was evaluated according to its L* value. The obtained results were transformed into ranks of L* values, and then normalized to the ratio of the selected area to the plate area to obtain the pigmentation score.

[0292] Results for skin sections were averaged.

[0293] It should be noted that standardization was performed. Standardization implies that these extreme values ​​(the smallest and largest values) were excluded from further analysis. This helped to reduce the influence of potential “unusual values” and to correctly assess “genuine data”.

[0294] The details of the treatments on the skin samples for Examples 1 and 2 and Comparative Examples 1 to 4 were as shown in the following Table 2.

[0295] [Table 2]Table 2 Ex. comp. 1 Ex. comp. 2 Ex. comp. 3 Ex. comp. 4 comp. 1 comp. 2 Application of compositio nA No Yes No Yes Yes Yes Application of the micro-needle device No No Yes Yes Yes Yes Number of applications of the microneedle device (per week) - - 3 3 3 2 Number of passes of the microneedle device during each application - - 5 5 2 5

[0296] The results are shown in [Fig. 1].

[0297] (Summary)

[0298] Comparative Examples 3 and 4 show that the use of the above microneedle device with or without composition A 3 times / week and 5 passes (each time the microneedle device was used) caused propigmentation effects on the skin.

[0299] On the other hand, Examples 1 and 2 show that the pro-pigmentation effects can be reduced by decreasing the frequency of application of the microneedle device or the number of passes of the microneedle device during its application to the skin. Thus, the optimal routine for the microneedle device may be 3 times / week with 2 passes or 2 times / week with 5 passes. Example 3 and comparative examples 5 to 7

[0300] (Microneedle Device)

[0301] A square microneedle sheet (5 mmx5 mm square) with 7x7 microneedles on a substrate sheet was used. Each microneedle was in the shape of a pyramid with a length or height of 80 pm and a base width of 40 pm. The microneedles were made of single-crystal silicon.

[0302] The square microneedle sheet was mounted on a head (first end) of a device as shown in WO 2011 / 115602, in which the head can vibrate with the axis of the device, to prepare a microneedle device which can apply the microneedle sheet to the skin with a vibration action toward the skin so that the microneedles can repeatedly penetrate the skin.

[0303] (Composition)

[0304] The following composition B shown in Table 3 was prepared by mixing the substances shown in Table 3.

[0305] [Table 3]Table 3 Composition B Weight (%) Caprylyl glycol 0.5 Preservative qs Hydroxyethylpiperazine ethanesulfonic acid 5 Propylene Glycol 2 Glycerin 3 Butylene glycol 10 Hydroxyethyl urea 5 Allantoin 0.3 Niacinamide 5 Xanthan gum 0.15 Phenylethyl resorcinol (Symwhite 377®) 0.3 Tranexamic acid 1 Water qs 100

[0306]

[0307] (Evaluation) First, for Example 3 and Comparative Examples 5 to 7, a human cadaver skin with a shape of 1.5 cm x 1.5 cm square was provided as a skin sample.

[0308] Second, for Example 3 and Comparative Example 6, Composition B was applied to one site (1 cmxl cm square) on the above skin sample.

[0309] Third, for Example 3 and Comparative Example 7, the above skin sample was treated by the above microneedle device. Specifically, the above microneedle device was used to apply the microneedle sheet to the above site on the skin sample so that the microneedles repeatedly penetrate the above site on the skin sample, with vibration of a frequency of 5,000 times per minute, and linear motion such as 2 strokes every 8 seconds to cover the above site on the skin sample once (one pass).

[0310] Next, for Example 3 and Comparative Examples 5 to 7, twelve skin sections (in the form of thin plates) were obtained by slicing the above skin sample. The twelve skin sections were stained by a modified Fontana-Masson stain to stain the melanin and argentaffin granules in the skin sections black / dark gray / brown. Then, the skin sections were analyzed by pigmentation analysis, as follows.

[0311] Pigmentation analysis: The amount of melanin present in each section was evaluated by estimating the intensity and distribution of the gray tint. Briefly, an 8-bit grayscale image was obtained by microscopic observation of the section. Then, the color space of the image was transformed from the system RGB in L*a* b* system, and each pixel of each image was evaluated according to its L* value. The results obtained were transformed into ranks of L* values, then normalized on the ratio between the selected surface and the surface of the plate in order to obtain the pigmentation score.

[0312] Results for skin sections were averaged.

[0313] It should be noted that standardization was performed. Standardization implies that these extreme values ​​(the smallest and largest values) were excluded from further analysis. This helped to reduce the influence of potential “unusual values” and to correctly assess “genuine data”.

[0314] The details of the treatments on the skin samples for Example 3 and Comparative Examples 5 to 7 were as shown in the following Table 4.

[0315] [Table 4] Table 4 Ex. comp. 5 Ex. comp. 6 Ex. comp. 7 comp. 3 Application of composition B No Yes No Yes Application of the micro-needle device s No No Yes Yes Number of applications of the micro-needle device (per week) - - 2 2 Number of passes of the micro-needle device during each application - - 5 5

[0316] The results are shown in [Fig.2].

[0317] (Summary)

[0318] Example 3 and Comparative Examples 5-7 show that controlled use of the microneedle device can prevent propigmentation, and that a combination of the use of Composition B and controlled use of the microneedle device can provide synergistic effects in reducing propigmentation effects on the skin.

Claims

Claims

1. A kit for cosmetically treating a keratinous substance, such as skin and lips, comprising: - at least one composition comprising at least one cosmetic active substance; - a microneedle sheet, comprising - a substrate sheet, and - a plurality of microneedles on the substrate sheet, - such that the microneedles can penetrate the keratinous substance, with a linear movement on the keratinous substance to make at least one pass on the keratinous substance, when applied to the keratinous substance;and - an instruction support including instructions which specify that - if the frequency of application of the microneedle sheet to the keratinous substance is 3 times per week, the number of passes of the microneedle sheet over the keratinous substance during each application is not 5, and - if the number of passes of the microneedle sheet over the keratinous substance during each application is 5, the frequency of application of the microneedle sheet over the keratinous substance is not 3 times per week.;

2. The kit of claim 1, wherein the kit further comprises a device for applying the microneedle sheet to the keratinous substance so that the microneedles can penetrate the keratinous substance.

3. A kit according to any one of claims 1 to 2, wherein the microneedles have a height of 10 to 300 micrometers, preferably 30 to 200 micrometers, and more preferably 50 to 100 micrometers.

4. A kit according to claim 3, wherein the base of the microneedles has a width of 10 to 150 micrometers, preferably 15 to 100 micrometers, and more preferably 20 to 50 micrometers.

5. A kit according to claim 4, wherein the ratio (height of the pyramid) / (width of the base of the pyramid) of the micro- needles is greater than or equal to 1, preferably greater than or equal to 1.5, and more preferably greater than or equal to 2.0.

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