Cosmetic process using microneedles

Abstract

The present invention relates to a cosmetic process for a keratin substance such as skin and lips, comprising the steps of: applying onto the keratin substance at least one composition comprising at least one cosmetic active ingredient; and applying onto the keratin substance 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 keratin substance, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, wherein the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week. Through the present invention, the risk of pigmentations due to the use of microneedles can be reduced.

Description

[0001] DESCRIPTION

[0002] TITLE OF INVENTION

[0003] COSMETIC PROCESS USING MICRONEEDLES

[0004] TECHNICAL FIELD

[0005] The present invention relates to the use of a plurality of microneedles for cosmetic treatments of a keratin substance such as skin and lips.

[0006] BACKGROUND ART

[0007] A use of different types of microneedles such as metallic, soluble, and hollow microneedles for enhancing the permeability of cosmetic active ingredients into the skin is well known. For example, WO 2019 / 100902 discloses a transdermal penetration dermal cosmetic method using microneedles in a combination of a cosmetic composition including some cosmetic active ingredients. In WO 2019 / 100902, the microneedles are used every night for 28 days.

[0008] DISCLOSURE OF INVENTION

[0009] It has been known that when using such microneedles, inflammations may be caused in skin, and therefore, there is a risk of generating pigmentation in the skin, which is known as post inflammatory hyper pigmentation. This may become particularly important when microneedles are used for treating hyperpigmentation of skin, such as melisma, dark circles, and age spots.

[0010] An objective of the present invention is to provide a cosmetic process using microneedles which can provide a keratin substance such as skin and lips with reduced risk of pigmentations due to the use of the microneedles.

[0011] The above objective can be achieved by a cosmetic process for a keratin substance such as skin and lips, comprising the steps of: applying onto the keratin substance at least one composition comprising at least one cosmetic active ingredient; and applying onto the keratin substance 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 keratin substance, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, wherein the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0012] The above step of applying the composition comprising at least one cosmetic active ingredient may be performed before the step of applying the microneedle sheet onto the keratin substance.

[0013] The cosmetic active ingredient may be selected from skin care active ingredients, preferably selected from the group consisting of depigmenting or whitening agents, anti-aging agents, and mixtures thereof, and more preferably selected from the group consisting of Vitamin B3 and derivatives thereof, ascorbic acid and derivatives thereof, resorcinol derivatives, tranexamic acid and derivatives thereof, hyaluronic acid ingredients, and mixtures thereof.

[0014] The cosmetic active ingredient may be selected from depigmenting or whitening agents, and preferably selected from the group consisting of niacinamide, phenyl ethyl resorcinol, tranexamic acid, and a mixture thereof.

[0015] The amount of the cosmetic active ingredient(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.

[0016] The microneedle may have a height of from 10 to 300 microns, preferably from 30 to 200 microns, and more preferably from 50 to 100 microns.

[0017] The microneedle may be in the shape of a pyramid.

[0018] The base of the microneedle may have a width of from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 20 to 50 microns.

[0019] The ratio of (the height of the pyramid) / (the width of the base of the pyramid) of the microneedle may be 1 or more, preferably 1.5 or more, and more preferably 2.0 or more.

[0020] The microneedles may be made from inorganic materials, preferably metals or non-metals, and more preferably silicon.

[0021] The present invention also relates to a kit for cosmetically treating a keratin substance, such as skin and lips, comprising: at least one composition comprising at least one cosmetic active ingredient; 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 keratin substance, with a linear movement on the keratin substance to make at least one passage on the keratin substance, when being applied onto the keratin substance; and an instruction medium including instructions that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0022] The kit may further comprise a device for applying the microneedle sheet onto the keratin substance such that the microneedles are capable of penetrating into the keratin substance.

[0023] The device in the above kit may be capable of applying the microneedle sheet with repetitions.

[0024] The present invention also relates to a use 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 a keratin substance, such as skin and lips, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, when being applied onto the keratin substance, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week, in combination with at least one composition comprising at least one cosmetic active ingredient, in order to provide the keratin substance with reduced risk of pigmentations.

[0025] BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 shows a schematic view of a microneedle device which is preferably used for the present invention.

[0027] Figure 2 shows the pigmentation scores of the cosmetic treatments according to Examples 1-2 and Comparative Examples 1-4.

[0028] Figure 3 shows the pigmentation scores of the cosmetic treatments according to Example 3 and Comparative Examples 5-7.

[0029] BEST MODE FOR CARRYING OUT THE INVENTION

[0030] After diligent research, the inventors have discovered that it is possible to provide a cosmetic process using microneedles which can provide a keratin substance such as skin and lips with reduced risk of pigmentations due to the use of the microneedles.

[0031] Thus, one aspect of the present invention is a cosmetic process for a keratin substance such as skin and lips, comprising the steps of: applying onto the keratin substance at least one composition comprising at least one cosmetic active ingredient; and applying onto the keratin substance 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 keratin substance, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, wherein the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0032] According to the present invention, the risk of pigmentations due to the use of microneedles can be reduced. Thus, possible pigmentations after using microneedles can be prevented or suppressed by the present invention.

[0033] The cosmetic process according to the present invention can provide the above effects regardless of a combined use of a composition including at least one cosmetic active ingredient such as a depigmenting or whitening agent. However, if the cosmetic process according to the present invention is combined with a composition comprising at least one cosmetic active ingredient, the risk of pigmentations can be further reduced.

[0034] According to the present invention, microneedles can penetrate into a keratin substance such as skin. Thus, the microneedles can puncture the surface of the keratin substance to create fine holes or passages through which the cosmetic active ingredient can go into the keratin substance such as skin. Thus, the cosmetic active ingredient can penetrate into the keratin substance through the fine holes or passages such that it can go into the stratum comeum and / or it may reach the bottom of the stratum comeum. Furthermore, the cosmetic active ingredient may pass through the stratum comeum to reach any one of the lower layers of the epidermis, such as a granular layer, a stratum spinosum and a basal layer. Therefore, the cosmetic active ingredient can easily be delivered into the keratin substance. This can provide effective cosmetic effects such as depigmenting or whitening effects.

[0035] Also, the cosmetic active ingredient which passes through the stratum comeum can relatively easily diffuse on or in the epidermis to uniformly distribute in the keratin substance.

[0036] Therefore, this can provide uniform cosmetic effects.

[0037] Since microneedles do not cause any pain, the cosmetic process according to the present invention can provide cosmetic treatments without pain. In addition, the cosmetic process according to the present invention can be performed in a relatively short period of time.

[0038] Thus, the present invention is convenient as cosmetic or non-therapeutic treatments.

[0039] Hereafter, the cosmetic process, kit, and the like according to the present invention will be described in a detailed manner.

[0040] [Cosmetic Process]

[0041] The cosmetic process according to the present invention for a keratin substance such as skin and lips, comprises the steps of: applying onto the keratin substance at least one composition comprising at least one cosmetic active ingredient; and applying onto the keratin substance 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 keratin substance, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, wherein the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0042] The cosmetic process according to the present invention may be intended for cosmetic treatments of a keratin substance such as skin and lips, preferably skin, and more preferably face skin.

[0043] The cosmetic process according to the present invention may be used to improve the aesthetic appearance of a keratin substance, for example, by depigmenting or whitening the keratin substance.

[0044] The cosmetic process according to the present invention can provide a keratin substance with reduced risk of pigmentations. Therefore, for example, when microneedles are used for cosmetically treating hyperpigmentation of the skin, such as melisma, dark circles, and age spots, the cosmetic treatments can be secured due to the reduced risk of new pigmentations by using the microneedles.

[0045] Hereafter, the microneedle sheet and the like used for the cosmetic process according to the present invention, as well as examples of how to perform the cosmetic process according to the present invention, will be explained in a detailed manner. {Composition}

[0046] The cosmetic process according to the present invention comprises the step of applying onto a keratin substance, such as skin and lips, at least one composition comprising at least one cosmetic active ingredient.

[0047] The step of applying onto a keratin substance at least one composition comprising at least one cosmetic active ingredient can be performed by using any applicator such as a brush.

[0048] It may be preferable that the composition including at least one cosmetic active ingredient be applied onto the keratin substance in combination of at least one porous sheet such as a woven or non-woven fabric, in order for good contact of the composition with the keratin substance and good cosmetic effects on the desired site of the keratin substance.

[0049] A porous sheet can absorb and maintain the composition comprising at least one cosmetic active ingredient. Therefore, applying a porous sheet can make it easy for the composition to contact the keratin substance well, and this can contribute to good cosmetic effects on the keratin substance.

[0050] The type of the above combination is not limited. Thus, a porous sheet may be applied onto the keratin substance before applying the composition on the keratin substance. Alternatively, a porous sheet may be applied onto the keratin substance after applying the composition on the keratin substance.

[0051] The step of applying onto a keratin substance, such as skin and lips, at least one composition comprising at least one cosmetic active ingredient, may be performed before or after the step of applying the microneedle sheet onto the keratin substance.

[0052] It is preferable that the step of applying onto a keratin substance, such as skin and lips, at least one composition comprising at least one cosmetic active ingredient, be performed before the step of applying the microneedle sheet onto the keratin substance. In other words, it is preferable that the composition be used as a pre-treatment composition for a keratin substance.

[0053] If the composition is used as a pre-treatment composition, it may be preferable that the microneedle sheet be applied onto the keratin substance without a step of drying the composition on the keratin substance. In other words, it may be preferable that the microneedle sheet be applied onto the keratin substance such that the microneedles are capable of penetrating into the keratin substance before the composition is dried or while the keratin substance is wet.

[0054] If the cosmetic process according to the present invention further comprises the step of removing the microneedles from the surface of the keratin substance, after the step of removing the microneedles from the surface of the keratin substance, the composition comprising at least one cosmetic active ingredient may be removed from the surface of the keratin substance.

[0055] However, it is preferable that the cosmetic process according to the present invention further comprises the step of maintaining or leaving the composition comprising at least one cosmetic active ingredient on the keratin substance after the step of removing the microneedles from the surface of the keratin substance and before the step of removing the composition from the surface of the keratin substance, because the composition can effectively penetrate into the keratin substance via the holes formed on and in the keratin substance by the microneedles.

[0056] The cosmetic active ingredient in the composition to be used for the cosmetic process according to the present invention may be selected from skin care active ingredients.

[0057] Thus, it is preferable that the composition to be used for the cosmetic process according to the present invention be a cosmetic composition, and more preferably a skin care cosmetic composition.

[0058] (Skin Care Active Ingredient)

[0059] The composition to be used for the cosmetic process according to the present invention may comprise, as the cosmetic active ingredient, at least one skincare active ingredient. If two or more skincare active ingredients are used, they may be the same or different.

[0060] The skin care active ingredient here is intended to mean an ingredient for enhancing the aesthetic appearance and / or comfort of the skin. In particular, the skin care active ingredient may be intended for attenuating visible irregularities (dyschromia, hyperpigmentations, etc.) and / or tactile irregularities (wrinkles, subcutaneous fat, comedones, acne scars, etc.) of the skin and / or for making the skin healthier, less greasy and / or less dry.

[0061] The skin care active ingredient here is not intended to mean an ingredient for providing the skin with chromatic color. Thus, the skin care active ingredient does not encompass a pigment or a dye.

[0062] It may be preferable that the skin care active ingredient 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.

[0063] A log P value is a value for the base-ten logarithm of the apparent octan-l-ol / water partition coefficient. The log p values are known and are determined by a standard test which determines the concentration of the compound in octan-l-ol and water. The log P may 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 may also be calculated using numerous commercially available software packages, which determine the log P as a function of the structure of a molecule. By way of example, mention may be made of the Epiwin software from the United States Environmental Agency.

[0064] The values may especially be calculated using the ACD (Advanced Chemistry Development) Solaris software V4.67; they may also be obtained from Exploring QSAR: hydrophobic, electronic and steric constants (ACS professional reference book, 1995). There is also an Internet site which provides estimated values (address: http : / / esc. syrres . com / interkow / kowdemo .htm) .

[0065] The skin care active ingredient may be in the form of a salt. The salts of the skin care active ingredient include conventional non-toxic salts of said compounds, such as those formed from an acid or from a base. It is preferable that the skin care active ingredient be a depigmenting or whitening agent, or an anti-aging agent such as an anti-wrinkle agent.

[0066] The depigmenting or whitening agent here is intended to mean any substance which can brighten the color of the skin or enhance the brightness of the surface of the skin.

[0067] As the depigmenting or whitening agent, mention may be made of Vitamin B3 and derivatives.

[0068] Vitamin B3, also called vitamin PP, is a compound of the following formula: in which R may be -CONH2 (niacinamide), -COOH (nicotinic acid or niacin), or CH2OH (nicotinyl alcohol), -CO-NH-CH2-COOH (nicotinuric acid) or -CO-NH-OH (niconityl hydroxamic acid). Niacinamide is preferable.

[0069] 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, products from reaction with carboxylic acids and amino acids, esters of nicotinyl alcohol and of carboxylic acids such as acetic acid, salicyclic acid, glycolic acid or palmitic acid.

[0070] Mention may also be made of the following derivatives: 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.

[0071] Other vitamin B3 derivatives that may also be mentioned include its inorganic salts, such as chlorides, bromides, iodides or carbonates, and its organic salts, such as the salts obtained by reaction with carboxylic acids, such as acetate, salicylate, glycolate, lactate, malate, citrate, mandelate, tartrate, etc.

[0072] As the depigmenting or whitening agent, mention may be made of ascorbic acid and derivatives thereof.

[0073] Ascorbic acid is generally in L form, since it is usually extracted from natural products.

[0074] On account of its chemical structure (a-keto lactone) which makes it very sensitive to certain environmental parameters such as light, heat and aqueous media, it may be advantageous to use the ascorbic acid in the form of a derivative or an analog chosen, for example, from saccharide esters of ascorbic acid or metal salts of phosphoryl ascorbic acid, alkali metal salts, esters and sugars.

[0075] The saccharide esters of ascorbic acid that may be used in the present invention are especially the glycosyl, mannosyl, fructosyl, fucosyl, galactosyl, N-acetylglucosamine and N- acetylmuramic derivatives of ascorbic acid, and mixtures thereof, and more especially ascorbyl glucoside such as ascorbyl-2 glucoside, 2-O-a-D-glucopyranosyl L-ascorbic acid or 6-O-[3-D-galactopyranosyl L-ascorbic acid. The latter compounds and processes for preparing them are described in particular in documents EP-A-0 487 404, EP-A-0 425 066 and JP 05 213 736.

[0076] With regard to the metal salt of phosphoryl ascorbic acid, it may be chosen from alkali metal, and especially sodium, ascorbyl phosphates, alkaline-earth metal ascorbyl phosphates and transition metal ascorbyl phosphates.

[0077] It is also possible to use ascorbic acid precursors such as active agent amides and active agent saccharide derivatives, which respectively involve proteases or peptidases and glycosidases as enzymes for releasing ascorbic acid in situ. Such compounds are described in patent EP 0 667 145.

[0078] The active agent saccharide derivatives are especially chosen from C3 to Ce saccharide derivatives. They are especially chosen from glucosyl, mannosyl, fructosyl, fucosyl, N- acetylglucosamine, galactosyl and N-acetylgalactosamine derivatives, N-acetylmuramic acid derivatives and sialic acid derivatives, and mixtures thereof.

[0079] The second ascorbic acid precursors may be chosen from derivatives that are hydrolyzed by other enzymes, for example by esterases, phosphatases, sulfatases, etc. According to the present invention, the second active agent precursors may be chosen, for example, from phosphates; sulfates; palmitates; acetates; propionates; ferulates, and, in general, active agent alkyl or acyl esters; acyl or alkyl ethers. The acyl and alkyl radicals in particular contain from 1 to 30 carbon atoms. As the skin care active ingredient, mention may be made of 3-O-ethyl ascorbic acid.

[0080] 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 phosphatase on contact with the skin, and the second precursor may be an acyl or alkyl ester derived from the reaction with an organic acid, for instance palmitic acid, acetic acid, propionic acid, nicotinic acid, 1,2,3- propanetricarboxylic acid or ferulic acid to react with a specific skin esterase.

[0081] Other derivatives are described, for example, in patent EP 1 430 883.

[0082] The ascorbic acid analogs are, more particularly, its salts, especially alkali metal salts, for example sodium ascorbate, its esters, especially such as its acetic, propionic or palmitic esters, or its sugars, especially such as glycosyl ascorbic acid.

[0083] As the depigmenting or whitening agent, mention may be made of resorcinol derivatives.

[0084] The resorcinol derivative may preferably be 4-position substituted derivatives, such as 4- alkylresorcinols, more preferably phenyl ethyl resorcinol, 4-n-butylresorcinol and 4- (tetrahydro-2H-pyran-4-yl) benzene- 1,3 -diol, and in particular phenyl ethyl resorcinol because of its whitening effect. Phenyl ethyl resorcinol is also referred to as 4-(l- phenylethyl)- 1,3 -benzenediol and represented by the following chemical formula. Phenyl ethyl resorcinol can be obtained, for example, from Symrise Corp (the product name: Symwhite 377®).

[0085]

[0086] 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,

[0087] 3.5 -dihydroxytoluene monohydrate, 4-chlororesorcinol, 2-chlororesorcinol, 2’, 4’- dihydroxyacetophenone, 3 ’ ,5 ’ -dihydroxyacetophenone, 2,6-dihydroxy-4- methylbenzaldehyde, 4-propylresorcinol, 2,4-dihydroxy-l,3,5-trimethylbenzene, 3,5- dihydroxybenzamide, 2,6-dihydroxybenzamide, 2,4-dihydroxybenzamide, 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, 3, 5 -dihydroxyacetophenone monohydrate, 3,5-dihydroxybenzylamine hydrochloride, 4,6-dichlororesorcinol, 2 ’,4 ’-dihydroxy-3 ’-methylpropiophenone, l-(3-ethyl-

[0088] 2.6-dihydroxyphenyl)ethan- 1 -one, 2 ’ ,6 ’ -dihydroxy-4 ’ -methoxyacetophenone, l-(2,6- dihydroxy-3-methoxyphenyl)ethan-l-one, 3(2,4-dihydroxyphenylpropionic acid, and 2,4- dihydroxy-3,6-dimethylbenzoic acid.

[0089] As the depigmenting or whitening agent, mention may also be made of tranexamic acid and derivatives thereof.

[0090] As examples of derivatives of tranexamic acid, mention may be made of dimmers of tranexamic acid (such as hydrochloric acid trans-4-(trans- aminomethylcyclohexanecarbonyl)aminomethylcyclohexane carboxylic acid), esters of tranexamic acid and hydroquinone (such as 4 ’-hydroxyphenyl trans-4- aminomethylcyclohexane carboxylate), esters of tranexamic acid and gentisic acid (such as 2- (trans-4-aminomethylcyclohexanecarbonyloxy)-5-hydroxybenzoic acid and salts thereof), tranexamic amides (such as trans-4-aminomethylcyclohexanecarboxylic acid methylamide and salts thereof, trans-4-(p-methoxybenzoyl)aminomethylcyclohexane carboxylic acid and salts thereof, and trans-4-guanidinomethylcyclohexane carboxylic acid and salts thereof), and the like.

[0091] It is preferable that the depigmenting or whitening agent be selected from the group consisting of niacinamide, phenylethyl resorcinol, tranexamic acid, and a mixture thereof. As the anti-aging agent, mention may be made of hyaluronic acid ingredients.

[0092] The hyaluronic acid ingredient may be selected from the group consisting of hyaluronic acid, hyaluronic acid salts, hyaluronic acid derivatives, hyaluronic acid derivative salts, and mixtures thereof.

[0093] Hyaluronic acid is a predominant glucosaminoglycan found in the skin. Thus, the fibroblasts synthesize predominantly collagens, matrix glycoproteins other than collagens (fibronectin, laminin), proteoglycans and elastin. The keratinocytes, for their part, synthesize predominantly sulfated glycosaminoglycans and hyaluronic acid. Hyaluronic acid is also called hyaluronan.

[0094] Hyaluronic acid is present in the free state in the epidermis and in the dermis and is responsible for turgescence of the skin. This polysaccharide can in fact retain a large volume of water, corresponding to up to 1000 times its weight. In this sense, hyaluronic acid plays an important role in increasing the amounts of water bound in the tissue, and also in the mechanical properties of the skin and in wrinkle formation.

[0095] Hyaluronic acid can be represented by the following chemical formula.

[0096] In the context of the present invention, the term "hyaluronic acid" covers in particular the basic unit of hyaluronic acid of formula:

[0097] It is the smallest fraction of hyaluronic acid comprising a disaccharide dimer, namely D- glucuronic acid and N-acetylglucosamine.

[0098] Hyaluronic acid derivatives may be selected from the group consisting of hydrolyzed hyaluronic acid, acetylated hyaluronic acid, cationic hyaluronic acid, and mixtures thereof.

[0099] 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. The examples of the cationic group include -CH2-CH(OH)-CH2- N+(CH3)3. Examples of the cationic hyaluronic acid includes hydroxypropyl trimonium hyaluronate.

[0100] As hyaluronic acid salts or hyaluronic acid derivative salts, mention may be made of alkaline metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salts, ammonium salts, and mixtures thereof.

[0101] The molecular weight of hyaluronic acid ingredient is not limited. The molecular weight of hyaluronic acid ingredient may be 5 kDa or more, preferably 20 kDa or more, and more preferably 100 kDa or more. The molecular weight of hyaluronic acid ingredient may be 20 MDa or less, preferably 10 MDa or less, and more preferably 2,000 kDa or less. Thus, the molecular weight of hyaluronic acid ingredient 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.

[0102] Unless otherwise defined in the descriptions, “molecular weight” may mean a number average molecular weight.

[0103] Hyaluronic acid ingredient 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: 6100 Da).

[0104] A single hyaluronic acid ingredient with a single molecular weight, or a combination of two or more hyaluronic acid ingredients with different molecular weights may be used.

[0105] In one embodiment of the present invention, the cosmetic active ingredient may be selected from skin care active ingredients, preferably selected from the group consisting of depigmenting or whitening agents, anti-aging agents, and mixtures thereof, and more preferably selected from the group consisting of Vitamin B3 and derivatives thereof, ascorbic acid and derivatives thereof, resorcinol derivatives, tranexamic acid and derivatives thereof, hyaluronic acid ingredients, and mixtures thereof.

[0106] In another embodiment of the present invention, the cosmetic active ingredient may be selected from depigmenting or whitening agents, and preferably selected from the group consisting of niacinamide, phenyl ethyl resorcinol, tranexamic acid, and a mixture thereof.

[0107] (Amount of Cosmetic Active Ingredient)

[0108] The amount of the cosmetic active ingredient(s) in the composition used for the cosmetic process according to the present invention is not limited.

[0109] The amount of the cosmetic active ingredient(s) in the composition to be used for the cosmetic process according to the present invention may be 0.001% by weight or more, preferably 0.01% by weight or more, and more preferably 0.1% by weight or more, relative to the total weight of the composition.

[0110] The amount of the cosmetic active ingredient(s) in the composition to be used for the cosmetic process according to the present invention may be 20% by weight or less, preferably 15% by weight or less, and more preferably 10% by weight or less, relative to the total weight of the composition.

[0111] Thus, the amount of the cosmetic active ingredient(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.

[0112] (Vehicle)

[0113] The composition to be used for the cosmetic process according to the present invention may comprise at least one vehicle.

[0114] The vehicle in the composition to be used for the cosmetic process according to the present invention is not limited.

[0115] For example, the vehicle may be selected from hydrophilic media and hydrophobic media.

[0116] 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 sugar 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.

[0117] The hydrophobic media may be selected from oils.

[0118] It may be preferable that the composition to be used for the cosmetic process according to the present invention comprise water.

[0119] The amount of the vehicle(s) in the composition to be used for the present invention may be 50% by weight or more, preferably 55% by weight or more, and more preferably 60% by weight or more, relative to the total weight of the composition.

[0120] The amount of the vehicle(s) in the composition to be used for the present invention may be 99% by weight or less, preferably 95% by weight or less, and more preferably 90% by weight or less, relative to the total weight of the composition.

[0121] The amount of vehicle(s) in the composition to be used for the present invention may range 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.

[0122] (Optional Ingredients)

[0123] The composition to be used for the cosmetic process according to the present invention may comprise, in addition to the aforementioned ingredients, additives typically employed in cosmetics, specifically, surfactants or emulsifiers, hydrophilic or lipophilic thickeners, natural extracts derived from animals or vegetables, waxes, and the like, within a range which does not impair the effects of the present invention. 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 from 0.01% to 50% by weight, preferably from 0.05% to 30% by weight, and more preferably from 0.1% to 10% by weight, relative to the total weight of the composition.

[0124] (Preparation)

[0125] The composition to be used for the present invention can be prepared by, for example, mixing cosmetic active ingredient(s) such as depigmenting or whitening agent(s), and vehicle(s), as essential ingredients, and optional ingredient(s), if necessary, as explained above.

[0126] The method and means to mix the above essential and optional ingredients are not limited. Any conventional method and means can be used to mix the above essential and optional ingredients to prepare the composition to be used for the present invention.

[0127] {Microneedle Sheet}

[0128] The cosmetic process according to the present invention comprises the step of applying onto a keratin substance, such as skin and lips, a microneedle sheet.

[0129] 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.

[0130] The microneedle sheet to be used for the present invention may be regarded as a cosmetic device, preferably a cosmetic device for a keratin substance, and more preferably a cosmetic device for skin, in particular face skin, as well as lips.

[0131] 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 onto a keratin substance, such as skin and lips, such that the microneedles are capable of penetrating into the keratin substance, with a linear movement on the keratin substance to make at least one passage on the keratin substance.

[0132] It is preferable that the linear movement be performed for a desired area on the keratin substance. For example, it is preferable that the applying site of the microneedle sheet can move in a linear direction on a desired area of the surface of the keratin substance, provided that the microneedles are capable of penetrating into the desired area on the keratin substance.

[0133] The cosmetic process according to the present invention may further comprise the step of removing the microneedles from the surface of the keratin substance.

[0134] (Microneedles)

[0135] The microneedle sheet to be used for the present invention comprises a plurality of microneedles.

[0136] 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 of the substrate sheet. It is preferable that the microneedles be present on one of the surfaces of a substrate sheet.

[0137] It is preferable that the microneedles of the microneedle sheet to be used for the present invention be designed to penetrate or enter into the stratum comeum of skin, in particular face skin, as well as lips.

[0138] A microneedle can be any suitable size and shape to puncture the stratum comeum. It may be preferable that the microneedles be designed to pierce and cross the stratum comeum. The microneedles may be capable of creating openings or passages in the stratum comeum.

[0139] If necessary, the height of the microneedles may be adjusted so as to allow penetration to the epidermis and / or dermis of the skin, preferably to the epidermis, and more preferably to any one of the layers in the epidermis.

[0140] 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 can 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 taper in diameter in the direction from the base to the tip.

[0141] For example, the shape of the microneedle may be in the form of a triangular pyramid, a square pyramid or a pentagonal pyramid. Alternatively, the microneedle may be in the form of a cylinder preferably with a tip which may be formed by diagonally cutting the cylinder. The cross section of the microneedle may take any geometric form including, circular, triangular, square, rectangular, polyhedral, regular or irregular forms, 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.

[0142] Thus, reference is made to "microneedles" as a type of microprotrusion or microprojection which is being employed. It will be understood by persons skilled in the art that in many cases the same inventive principles apply to the use of other microprotrusions or microprojections to penetrate the skin. Other microprotrusions or microprojections may include, for example, microblades as described in U.S. Patent No. 6,219,574 and Canadian Patent Application No. 2,226,718, and edged microneedles as described in U.S. Patent No. 6,652,478.

[0143] The height or length of the microneedle of the microneedle sheet to be used for the present invention may be from 10 to 300 microns, preferably from 30 to 200 microns, and more preferably from 50 to 100 microns.

[0144] According to one embodiment of the present invention, the microneedle is in the form of a cone.

[0145] The cone may comprise a distal end such as a tip, and a base. The shape of the base may be a circle or oval.

[0146] The height or length of the cone of the microneedle of the microneedle sheet to be used for the present invention may be from 10 to 300 microns, preferably from 30 to 200 microns, and more preferably from 50 to 100 microns. The base of the cone of the microneedle of the microneedle sheet to be used for the present invention may have a diameter or width of from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 20 to 50 microns. If the base of the cone of the microneedle of the microneedle sheet to be used for the present invention is in the shape of an oval or ellipse, the length of the major axis or width of the oval may be from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 20 to 50 microns.

[0147] The microneedle may have an aspect ratio (length / width at base) of at least about 3:1, at least about 2: 1 , or at least about 1:1. The ratio of (the height of the cone) / (the diameter of the base of the cone) of the microneedle may be 1 or more, preferably 1.5 or more, and more preferably 2.0 or more.

[0148] According to another embodiment of the present invention, the microneedle is in the form of a pyramid, such as a triangular pyramid and a square pyramid.

[0149] The pyramid may comprise a distal end such as a tip, and a base. The shape of the base may be a triangle or a square.

[0150] The height or length of the pyramid of the microneedle of the microneedle sheet to be used for the present invention may be from 10 to 300 microns, preferably from 30 to 200 microns, and more preferably from 50 to 100 microns.

[0151] The base of the pyramid of the microneedle of the microneedle sheet to be used for the present invention may have a width or side of from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 10 to 50 microns. If the base of the pyramid of the microneedle of the microneedle sheet to be used for the present invention is in the shape of a triangle or square, the length of the width or side of the triangle or square may be from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 20 to 50 microns.

[0152] The microneedle may have an aspect ratio (length / width at base) of at least about 3:1, at least about 2: 1, or at least about 1 :1. The ratio of (the height of the pyramid) / (the width of the base of the pyramid) of the microneedle may be 1 or more, preferably 1.5 or more, and more preferably 2.0 or more.

[0153] It may be preferable that the microneedle be capable of penetrating into a keratin substance, such as skin and lips, to a depth of 200 microns or less, preferably 180 microns or less, and more preferably 160 microns or less.

[0154] A very narrow pitch of microneedles may not provide the microneedles with sufficient surface area so that the microneedles may not penetrate inside the skin. On the other hand, too wide of a pitch may also cause an issue that the individual microneedle may not get enough pressure to penetrate. Thus, it may be preferable that a pitch of microneedle arrays be from 400 to 700 microns, and more preferably from 400 to 500 microns.

[0155] The number of the microneedles and the pitch between the microneedles depend on some factors such as desired color pattern and width of a microneedle. For example, if a color pattern with a 0.5 micron width is desired, the use of a microneedle sheet having a microneedle array (2x2) with a 0.5 mm pitch may be the most appropriate. In one embodiment, the density of microneedles may be from 100 to 2000 microneedles / cm2, preferably 200 to 1000 microneedles / cm2, and even more preferably 200 to 500 microneedles / cm2.

[0156] It is preferable that the microneedles are not dissolvable.

[0157] The “not dissolvable” microneedle means that the microneedle cannot break down or disintegrate inside a keratin substance such as skin and lips by, for example, a natural moisturizing factor or external moisture.

[0158] It is more preferable that the microneedles are not water-soluble.

[0159] The microneedles may be made from organic or inorganic materials. As examples of the organic materials, mention may be made of synthetic polymers including polyethylene, polypropylene and photoresists, biodegradable plastics, cellulose derivatives and mixtures thereof. As examples of the inorganic materials, mention may be made of metals including stainless steel, non-metals such as silicon, glass, and ceramics, and mixtures thereof. Also, any other materials which is implantable in skin or body may be used.

[0160] It is preferable that the microneedles be sterile or sterilized before use. It is more preferable that the microneedles be used for only once, and therefore be disposable.

[0161] It is preferable that the microneedles be made from inorganic materials, more preferably metals or non-metals, and even more preferably silicon (in particular, single crystal silicon).

[0162] It is also preferable that the microneedles be solid (non-hollow).

[0163] (Substrate Sheet)

[0164] The microneedle sheet to be used for the present invention comprises a substrate sheet on which the microneedles are present or placed.

[0165] The substrate sheet and the microneedles may be separated or integrated.

[0166] 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 can be a single element comprising at least one common material. Preferably, the single element can be prepared by using the same material.

[0167] 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 from different materials. In this case, the substrate sheet may be, for example, chosen from masks, wipes, patches, and in general all types of porous substrate sheets. Preferably, these substrate sheets have an oblong structure, namely with a thickness smaller than the dimensions of the plane in which they are defined.

[0168] The substrate sheet may be cut so as to be in the form of a patch, a disc, a mask, a towel, a glove, a precut roll, or any other form suitable for a cosmetic use.

[0169] (Preparation) There is no limitation regarding 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 based on conventional technology such as molding, 3D printing, metal processing, and the like.

[0170] The shape of the microneedle sheet to be used for the cosmetic process according to the present invention is not limited, and it may be any shape such as the shape of the lips or a shape suitable for application under the eyes, depending on the application target of the microneedle sheet.

[0171] {Device}

[0172] In the cosmetic process according to the present invention, the microneedle sheet is applied onto a keratin substance such as skin and lips such that the microneedles are capable of penetrating into the keratin substance.

[0173] It is preferable that the microneedles be capable of penetrating into the keratin substrate with repetitions.

[0174] How to perform repeating penetrations of microneedles into a keratin substance is not limited. For example, the repeating penetrations may be performed by tapping the back surface of the substrate sheet of the microneedle sheet with fingers several times such that the microneedles on the front surface of the substrate sheet can repeatedly penetrate into the keratin substance.

[0175] Furthermore, it is preferable to perform the repeating penetrations of microneedles by using vibration toward a keratin substance such as skin and lips.

[0176] For example, as shown in Fig. 1, a microneedle sheet 1 can be connected to an oscillator 2 which can produce vibration toward the surface of a keratin substance which corresponds to the direction of up and down in Fig. 1. The type of the oscillator 2 is not limited as long as it can produce vibration. For example, the oscillator 2 may be constituted by a piezo electric element. Of course, any other actuator which can repeatedly move, preferably vibrate, toward a keratin substance can be used instead of the oscillator 2.

[0177] In Fig. 1 , the microneedle sheet 1 can move up and down based on the vibration caused by the oscillator 2, and therefore, the microneedles on the microneedle sheet 1 can repeatedly penetrate into a keratin substance such as skin and lips.

[0178] It is preferable that the oscillator 2 be linked with a head which can function as a receptor for the microneedle sheet 1 , and that the substrate sheet of the microneedle sheet 1 is attached to the head. Thus, the vibration caused by the oscillator 2 can be conveyed to the head. Then, the microneedle sheet 1 can also vibrate via the head.

[0179] It is preferable to use a device in order to vibrate the microneedle sheet 1. For example, the device may comprise the oscillator 2 and the head which is linked with the oscillator 2 as well as a battery, such as a dry cell, which can drive the oscillator 2 and a control means to control the frequency of the vibration caused by the oscillator 2. As an example, a device disclosed in WO 2011 / 115602, the content of which is incorporated herein by reference, may be used as the above device. When using the above device, the microneedle sheet 1 can be mounted on the head of the device, and can be applied onto a keratin substance such as skin and lips such that the microneedles of the microneedle sheet 1 can repeatedly penetrate into the keratin substance.

[0180] The vibrating or tapping frequency is not limited. For example, the frequency may be from 1000 to 10000 per minute, preferably from 1000 to 8000 per minute, and more preferably from 3000 to 6000 per minute.

[0181] It may be preferable to control the pressure to be used for penetrating the microneedles into a keratin substance. The pressure can depend on some factors such as the type of microneedles.

[0182] The tapping or vibrating penetration of microneedles enables continuous and stable skin puncture, and can reduce the force required to drive the microneedle into the keratin substance. It may further provide massage effects to the treated area of the keratin substance.

[0183] {How to Perform the Cosmetic Process}

[0184] 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 onto a keratin substance, such as skin, such that the microneedles are capable of penetrating into the keratin substance, with a linear movement on the keratin substance to make at least one passage on the keratin substance.

[0185] According to the present invention, the above application satisfies the following conditions: the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0186] The control of application frequency and number of passages in each application in the cosmetic process according to the present invention can reduce the risk of pigmentation due to the use of microneedles.

[0187] Thus, for example, if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application may be 4 or less, preferably 3 or less, and more preferably 2 or less.

[0188] On the other hand, for example, if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance may be 2 times per week, and preferably 1 time per week. It may be preferable that, in the cosmetic process according to the present invention, the frequency of applying the microneedle sheet onto the keratin substance be 3 times per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 2.

[0189] It may be preferable that, in the cosmetic process according to the present invention, the frequency of applying the microneedle sheet onto the keratin substance be 2 times per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5.

[0190] [Kit and Use]

[0191] The present invention also relates to a kit for cosmetically treating a keratin substance, such as skin and lips, comprising: at least one composition comprising at least one cosmetic active ingredient; 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 keratin substance, with a linear movement on the keratin substance to make at least one passage on the keratin substance, when being applied onto the keratin substance; and an instruction medium including instructions that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

[0192] The above medium may be, for example, a sheet made of any material such as a paper.

[0193] The above explanations for the composition and the microneedle sheet for the cosmetic process according to the present invention can also apply to those in the kit according to the present invention.

[0194] The kit may further comprise a device for applying the microneedle sheet onto the keratin substance such that the microneedles are capable of penetrating into the keratin substance.

[0195] The above explanations for the device which may be used for the cosmetic process according to the present invention can also apply to the device which may be used for the kit according to the present invention.

[0196] It is preferable that the device be capable of applying the microneedle sheet with repetitions. For example, the device may comprise at least one element which is capable of vibrating or tapping the microneedle sheet. This element may correspond to the back surface of the substrate sheet if tapping with fingers is used for repeating the penetration of microneedles into a keratin substance, and to the oscillator 2 in Fig. 1 explained above if vibration is used for repeating the penetration of microneedles into a keratin substance.

[0197] The composition comprising at least one cosmetic active ingredient may be contained in any container such as a vessel which is commonly used for cosmetic purposes.

[0198] The kit can preferably be used for performing a cosmetic process according to the present invention.

[0199] The present invention also relates to a use 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 a keratin substance, such as skin and lips, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, when being applied onto the keratin substance, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week, in combination with at least one composition comprising at least one cosmetic active ingredient, in order to provide the keratin substance with reduced risk of pigmentations.

[0200] The above explanations for the composition and the microneedle sheet for the cosmetic process according to the present invention can also apply to those in the use according to the present invention.

[0201] Specifically, the use according to the present invention may comprise the first application onto the keratin substance the at least one composition comprising at least one cosmetic active ingredient; and the second application onto the keratin substance, to which the composition has been applied, 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 keratin substance, in order to provide the keratin substance with reduced risk of pigmentations.

[0202] It is preferable that the microneedles be capable of penetrating into the keratin substrate with repetitions. The repetitions may be based on the vibrating or tapping of the microneedle sheet.

[0203] Another aspect of the use of according to the present invention may be a composition comprising at least one cosmetic active ingredient, preferably at least one depigmenting or whitening agent, for use in reducing the risk of pigmentations, in combination with a microneedle sheet comprising a substrate sheet and a plurality of microneedles on the substrate sheet wherein the microneedles are capable of penetrating into the keratin substance. According to the above kit and use according to the present invention, the microneedles of a microneedle sheet can deliver the cosmetic active ingredient into a keratin substance such as skin and lips to provide the keratin substance with cosmetic effects. If the cosmetic active ingredient is a depigmenting or whitening agent, the above kit and use according to the present invention can provide a keratin substance such as skin with depigmenting or whitening effects. If the cosmetic active ingredient is an anti-aging agent, such as an antiwrinkle agent, the above kit and use according to the present invention can provide a keratin substance such as skin with anti-aging effects such as anti-wrinkle effects.

[0204] EXAMPLES

[0205] The present invention will be described in a more detailed manner 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 in the field of the present invention.

[0206] Examples 1-2 and Comparative Examples 1-4

[0207] (Microneedle Device)

[0208] A square microneedle sheet (5 mmx5 mm square) with 7^7 microneedles on a substrate sheet was used. Each microneedle had a shape of a pyramid with a length or height of 80 pm and a base width of 40 pm. The microneedles were made from single crystal silicon.

[0209] The square microneedle sheet was mounted on a head (first end) of a device as shown in WO 2011 / 115602, wherein the head can vibrate along with the axis of the device, to prepare a microneedle device which can apply the microneedle sheet onto skin with vibration action toward the skin such that the microneedles can repeatedly penetrate into the skin.

[0210] (Composition)

[0211] The following Composition A shown in Table 1 was prepared by mixing the ingredients shown in Table 1.

[0212] Table 1

[0213] (Evaluation)

[0214] First, for Examples 1-2 and Comparative Examples 1-4, a human cadaver skin with a shape of 1.5 cmx 1.5 cm square was provided as a skin sample.

[0215] Second, for Examples 1-2 and Comparative Examples 2 and 4, Composition A was applied onto a site (1 cmxl cm square) on the above skin sample. Third, for Examples 1-2 and Comparative Examples 3-4, the above skin sample was treated by the above microneedle device. Specifically, the above microneedle device was used to apply the microneedle sheet onto the above site on the skin sample such that the microneedles repeatedly penetrated into the above site on the skin sample, with a vibration of a frequency of 5000 times per minute, and a linear motion such that 2 strokes per 8 seconds to cover once (one passage) the above site on the skin sample.

[0216] Next, for Examples 1-2 and Comparative Examples 1-4, twelve skin sections (in the form of thin plates) were obtained by slicing the above skin sample. The twelve skin sections were colored by a modified Fontana-Masson staining to stain the melanin and argentaffin granules in the skin sections to be black / dark-grey / brown. Then, the skin sections were analyzed by the pigmentation analysis, as follows.

[0217] Pigmentation Analysis: The amount of melanin present in each section was evaluated by estimating the intensity and the distribution of grey tone. Briefly, an 8 bit grey-scale image was obtained by a microscope observation of the section. Then, the color space of the image was transformed from RGB system into L*a* b* system, and each pixel of each image was evaluated according to its L* value. The obtained results were transformed in ranks of L* values, and then normalized on the ratio between the selected area and the area of the plate to obtain pigmentation score.

[0218] The results for the skin sections were averaged.

[0219] It should be noted that a standardization was performed. The standardization involved in that extreme values (the smallest and largest values) were excluded from subsequent analysis.

[0220] This allowed to reduce the influence of potential "unusual values" and properly evaluating the "genuine data".

[0221] The details of the treatments on the skin samples for Examples 1 -2 and Comparative Examples 1-4 were as shown in the following Table 2.

[0222] Table 2

[0223] The results are shown in Fig. 1.

[0224] (Summary) Comparative Examples 3 and 4 show that the use of the above microneedle device with or without Composition A in 3 times / week and 5 passages (in each use of the microneedle device) caused pro-pigmentation effects on the skin.

[0225] On the other hand, Examples 1 and 2 show that the pro-pigmentation effects can be reduced by reducing frequency in the application of the microneedle device or the number of passages of the microneedle device during the application thereof onto the skin. Thus, the optimal routine for the microneedle device can be 3 times / week with 2 passages or 2 times / week with 5 passages.

[0226] Example 3 and Comparative Examples 5-7

[0227] (Microneedle Device)

[0228] A square microneedle sheet (5 m x5 mm square) with 7x7 microneedles on a substrate sheet was used. Each microneedle had a shape of a pyramid with a length or height of 80 pm and a base width of 40 pm. The microneedles were made from single crystal silicon.

[0229] The square microneedle sheet was mounted on a head (first end) of a device as shown in WO 2011 / 115602, wherein the head can vibrate along with the axis of the device, to prepare a microneedle device which can apply the microneedle sheet onto skin with vibration action toward the skin such that the microneedles can repeatedly penetrate into the skin.

[0230] (Composition)

[0231] The following Composition B shown in Table 3 was prepared by mixing the ingredients shown in Table 3.

[0232] Table 3

[0233] (Evaluation)

[0234] First, for Example 3 and Comparative Examples 5-7, a human cadaver skin with a shape of 1.5 cmxl.5 cm square was provided as a skin sample. Second, for Example 3 and Comparative Example 6, Composition B was applied onto a site (1 cm* 1 cm square) on the above skin sample.

[0235] 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 onto the above site on the skin sample such that the microneedles repeatedly penetrated into the above site on the skin sample, with a vibration of a frequency of 5000 times per minute, and a linear motion such that 2 strokes per 8 seconds to cover once (one passage) the above site on the skin sample.

[0236] Next, for Example 3 and Comparative Examples 5-7, twelve skin sections (in the form of thin plates) were obtained by slicing the above skin sample. The twelve skin sections were colored by a modified Fontana-Masson staining to stain the melanin and argentaffin granules in the skin sections to be black / dark-grey / brown. Then, the skin sections were analyzed by the pigmentation analysis, as follows.

[0237] Pigmentation Analysis: The amount of melanin present in each section was evaluated by estimating the intensity and the distribution of grey tone. Briefly, an 8 bit grey-scale image was obtained by a microscope observation of the section. Then, the color space of the image was transformed from RGB system into L*a* b* system, and each pixel of each image was evaluated according to its L* value. The obtained results were transformed in ranks of L* values, and then normalized on the ratio between the selected area and the area of the plate to obtain pigmentation score.

[0238] The results for the skin sections were averaged.

[0239] It should be noted that a standardization was performed. The standardization involved in that extreme values (the smallest and largest values) were excluded from subsequent analysis.

[0240] This allowed to reduce the influence of potential "unusual values" and properly evaluating the "genuine data".

[0241] The details of the treatments on the skin samples for Example 3 and Comparative Examples 5-7 were as shown in the following Table 4.

[0242] Table 4

[0243] The results are shown in Fig. 2.

[0244] (Summary) Example 3 and Comparative Examples 5-7 show that the controlled use of the microneedle device can prevent pro-pigmentation, and that a combination of the use of Composition B and the controlled use of the microneedle device can provide synergistic effects in reducing propigmentation effects on the skin.

Claims

CLAIMS1. A cosmetic process for a keratin substance such as skin and lips, comprising the steps of: applying onto the keratin substance at least one composition comprising at least one cosmetic active ingredient; and applying onto the keratin substance 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 keratin substance, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, wherein the frequency of applying the microneedle sheet onto the keratin substance is 3 times or less per week, and the number of passages of the microneedle sheet on the keratin substance during each application is 5 or less, provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

2. The cosmetic process according to Claim 1, wherein the step of applying the composition comprising at least one cosmetic active ingredient is performed before the step of applying the microneedle sheet onto the keratin substance.

3. The cosmetic process according to Claim 1 or 2, wherein the cosmetic active ingredient is selected from skin care active ingredients, preferably selected from the group consisting of depigmenting or whitening agents, anti-aging agents, and mixtures thereof, and more preferably selected from the group consisting of Vitamin B3 and derivatives thereof, ascorbic acid and derivatives thereof, resorcinol derivatives, tranexamic acid and derivatives thereof, hyaluronic acid ingredients, and mixtures thereof.

4. The cosmetic process according to any one of Claims 1 to 3, wherein the cosmetic active ingredient is selected from depigmenting or whitening agents, and preferably selected from the group consisting of niacinamide, phenyl ethyl resorcinol, tranexamic acid, and a mixture thereof.

5. The cosmetic process according to any one of Claims 1 to 4, wherein the amount of the cosmetic active ingredient(s) is 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.

6. The cosmetic process according to any one of Claims 1 to 5, wherein the microneedle has a height of from 10 to 300 microns, preferably from 30 to 200 microns, and more preferably from 50 to 100 microns.

7. The cosmetic process according to any one of Claims 1 to 6, wherein the microneedle is in the shape of a pyramid.

8. The cosmetic process according to Claim 7, wherein the base of the microneedle has a width of from 10 to 150 microns, preferably from 15 to 100 microns, and more preferably from 20 to 50 microns.

9. The cosmetic process according to Claim 7 or 8, wherein the ratio of (the height of the pyramid) / (the width of the base of the pyramid) of the microneedle is 1 or more, preferably 1.5 or more, and more preferably 2.0 or more.

10. The cosmetic process according to any one of Claims 1 to 9, wherein the microneedles are made from inorganic materials, preferably metals or non-metals, and more preferably silicon.

11. The cosmetic process according to any one of Claims 1 to 10, wherein the microneedles are capable of penetrating into the keratin substance with repetitions.

12. A kit for cosmetically treating a keratin substance, such as skin and lips, comprising: at least one composition comprising at least one cosmetic active ingredient; 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 keratin substance, with a linear movement on the keratin substance to make at least one passage on the keratin substance, when being applied onto the keratin substance; and an instruction medium including instructions that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week.

13. The kit according to Claim 12, wherein the kit farther comprises a device for applying the microneedle sheet onto the keratin substance such that the microneedles are capable of penetrating into the keratin substance.

14. The kit according to Claim 13, wherein the device is capable of applying the microneedle sheet with repetitions.

15. A use 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 a keratin substance, such as skin and lips, with a linear movement of the microneedle sheet on the keratin substance to make at least one passage of the microneedle sheet on the keratin substance, when being applied onto the keratin substance,provided that if the frequency of applying the microneedle sheet onto the keratin substance is 3 times per week, the number of passages of the microneedle sheet on the keratin substance during each application is not 5, and if the number of passages of the microneedle sheet on the keratin substance during each application is 5, the frequency of applying the microneedle sheet on the keratin substance is not 3 times per week, in combination with at least one composition comprising at least one cosmetic active ingredient, in order to provide the keratin substance with reduced risk of pigmentations.

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