HK1076385B - Composition for improving melasma and composition for reducing skin dullness - Google Patents

Description

Composition for improving melasma and composition for reducing skin dullness

Technical Field

The present invention relates to a composition effective in ameliorating black spot. The invention also relates to a method for improving melasma. Further, the present invention relates to a composition effective for reducing skin dullness. The invention also relates to a method for reducing skin dullness.

Background

Melasma is a disorder that occurs primarily in women and produces a brownish, symmetrical area of pigmentation on both sides of the face, but without accompanying inflammation. The cause of this disorder is not completely elucidated, but melasma formation is mainly due to various endocrine (polyenrcrene) abnormalities caused by estrogen, adrenocortical hormone, ACTH, etc., and is associated with solar radiation, pregnancy, ovarian dysfunction, oral contraceptive, antiepileptic, etc.

The conventional treatment of melasma is to remove both endogenous and exogenous causes of the disorder by: (1) oral administration of vitamin C or glutathione-reducing agents, (2) removal of etiological agents such as drugs, and (3) avoidance of solar radiation by the use of sunscreens (Hyojun hifukaku, 4 th edition, pp212-213, edited by Yoshio SATO, published by Igaku-Shoin). However, these conventional treatments have not produced satisfactory results and are therefore unsatisfactory.

Dullness of the skin is a serious aesthetic problem, especially for women, which is mainly indicative of some skin conditions, such as loss of clarity of the skin, skin cloudiness due to accumulation of in vivo waste, and uneven skin color. Dullness of the skin can be caused by a combination of factors such as skin cloudiness or skin melasma due to thickening of the keratinocyte layer and accompanying aging, reduction in skin redness, pigmentation, reduction in skin elasticity, skin yellowing, dirt such as sweat and sebum, and the like.

As described above, since the skin dullness is caused by the participation of various factors, the skin dullness cannot be effectively reduced even by the substances which have been considered useful for removing the yellowish-brown spot. Various substances useful for reducing skin dullness have been examined so far, but a substance that satisfactorily reduces skin dullness has not been developed yet.

Purine nucleic acid-related substances have been reported to exhibit various physiological functions, but it is not known that these substances can ameliorate yellowish-brown spots and lighten dullness of skin.

Purine nucleic acid-related substances are known to be difficult to formulate. When a relevant substance is mixed in the composition to a concentration at which it shows utility, the prepared composition is inferior in use touch, stability, etc. In particular, the substances are difficult to incorporate into emulsions due to their property of reducing the strength of the film formed at the water-oil interface. Thus, in order to formulate the substance into an emulsion such as an emulsion or a cream, it is necessary to develop a method for improving the stability of the emulsion.

Disclosure of the invention

It is an object of the present invention to provide a composition effective in improving melasma, and a composition z in the form of an oil/water emulsion which has good stability and is effective in improving melasma. It is another object of the present invention to provide a method for effectively improving melasma.

It is a further object of the present invention to provide a composition which is effective in reducing skin dullness and which has good stability in the form of an oil/water emulsion and is effective in reducing skin dullness. It is another object of the present invention to provide a method for effectively reducing skin dullness.

The present inventors have conducted intensive studies to solve the above-mentioned problems, and have found that a purine nucleic acid-related substance present in a living body, particularly adenosine monophosphate, i.e., adenosine monophosphate, or a salt thereof, is excellent in the improvement of melasma and the reduction of skin dullness. Further, the inventors of the present invention have found that excellent emulsification stability can be obtained for such purine nucleic acid-related substances which have hitherto been difficult to emulsify without losing their efficacy by preparing an oil/water emulsion by mixing the above-mentioned purine nucleic acid-related substance with a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and an oil component. Based on these findings, the inventors of the present invention have conducted further studies and completed the present invention.

More specifically, the present invention relates to the following compositions for improving melasma:

the composition for ameliorating melasma, which comprises a purine nucleic acid-related substance and a pharmaceutically or cosmetically acceptable carrier.

The composition for improving melasma according to item 1, wherein the purine nucleic acid-related substance is adenosine monophosphate or a salt thereof.

Item 3. the composition for improving melasma according to item 1 or 2, which contains the purine nucleic acid-related substance at a ratio of at least 0.01 wt% based on the total amount of the composition.

Item 4. the composition for improving melasma according to any one of items 1 to 3, which contains the purine nucleic acid-related substance at a ratio of 1 to 10 wt% based on the total amount of the composition.

The composition for improving black spot according to any one of items 1 to 4, wherein the composition has a pH ranging from 2 to 8.

The composition for improving melasma according to any one of items 1 to 5, for use in a medicine or quasi-medicine for external application, or a cosmetic.

The composition for improving black spot according to any one of items 1 to 6, wherein the composition further comprises a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and an oil, and is formulated into an oil/water-type emulsion.

Item 8 the composition for improving black spot according to item 7, further comprising a polyol.

Item 9 the composition for improving melasma according to item 7 or 8, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a polymerization degree of 6 or more.

The composition for improving black spot according to any one of items 7 to 9, wherein the alkanoyl lactic acid has an alkanoyl group with 8 or more carbon atoms.

Item 11. the composition for improving black spot according to any one of items 7 to 10, wherein the acrylic acid-alkyl methacrylate copolymer contains C_5-40An alkyl group.

The composition for improving black spot according to any one of items 7 to 11, wherein the oil is a hydrocarbon-based liquid oil.

The composition for improving melasma according to any one of items 7 to 12, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a degree of polymerization of 6 or more, the alkanoyl lactic acid containing an alkanoyl group having 8 or more carbon atoms, the acrylic-methacrylic acid alkyl ester copolymer containing C_5-40Alkyl, and the oil is a hydrocarbon liquid oil.

Item 14. the composition for improving black spot according to item 8, wherein the polyglycerin fatty acid ester is contained in a ratio of 0.05 to 6% by weight, the alkanoyl lactic acid or salt thereof is contained in a ratio of 0.01 to 1% by weight, the acrylic acid-alkyl methacrylate copolymer is contained in a ratio of 0.01 to 0.8% by weight, the oil-containing ratio is 0.3 to 20% by weight, the polyol is contained in a ratio of 0.05 to 15% by weight, and the water is contained in a ratio of 50 to 90% by weight, based on the total amount of the composition.

Item 15 the composition for improving black spot according to any one of items 7 to 14, wherein the polyglycerin fatty acid ester and the alkanoyl lactic acid or salt thereof are contained in a weight ratio of 95: 5 to 60: 40.

The composition for improving melasma according to any one of items 7 to 15, further comprising a lower alcohol.

The invention also relates to the following compositions for reducing skin dullness:

the composition for reducing skin dullness, which contains a purine nucleic acid-related substance, and a pharmaceutically or cosmetically acceptable carrier.

The composition for reducing skin dullness according to item 17, wherein the purine nucleic acid-related substance is adenosine monophosphate or a salt thereof.

The composition for reducing skin dullness according to item 17 or 18, which contains the purine nucleic-acid-related substance in a ratio of at least 0.01 wt% based on the total amount of the composition.

The composition for reducing skin dullness according to any one of items 17 to 19, which contains the purine nucleic acid-related substance at a ratio of 1 to 10 wt% based on the total amount of the composition.

The composition for reducing skin dullness according to any one of items 17 to 20, wherein the composition has a pH ranging from 2 to 8.

The composition for reducing skin dullness according to any one of items 17 to 21, which is used for a drug or quasi-drug for external application, or a cosmetic.

The composition for reducing skin dullness according to any one of items 17 to 22, wherein the composition further contains a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and an oil, and is formulated into an oil/water type emulsion.

The composition for reducing skin dullness according to item 23, further comprising a polyhydric alcohol.

The composition according to item 25, item 23 or 24, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a polymerization degree of 6 or more.

The composition for reducing skin dullness according to any one of items 23 to 25, wherein the alkanoyl lactic acid contains an alkanoyl group having 8 or more carbon atoms.

The composition for reducing skin dullness according to any one of items 23 to 26, wherein the acrylic acid-methacrylic acidThe alkyl ester copolymer contains C_5-40An alkyl group.

The composition for reducing skin dullness according to any one of items 23 to 27, wherein the oil is a hydrocarbon-based liquid oil.

The composition for relieving skin dullness according to item 29, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a degree of polymerization of 6 or more, the alkanoyl lactic acid containing an alkanoyl group having 8 or more carbon atoms, the acrylic-methacrylic acid alkyl ester copolymer containing C_5-40Alkyl, and the oil is a hydrocarbon liquid oil.

The composition according to item 24, wherein the polyglycerin fatty acid ester is contained in a ratio of 0.05 to 6% by weight, the alkanoyl lactic acid or salt thereof is contained in a ratio of 0.01 to 1% by weight, the acrylic acid-alkyl methacrylate copolymer is contained in a ratio of 0.01 to 0.8% by weight, the oil is contained in a ratio of 0.3 to 20% by weight, the polyhydric alcohol is contained in a ratio of 0.05 to 15% by weight, and the water is contained in a ratio of 50 to 90% by weight, based on the total amount of the composition.

The composition for reducing skin dullness according to any one of items 23 to 30, wherein the weight ratio of the polyglycerin fatty acid ester and the alkanoyl lactic acid or salt thereof is 95: 5 to 60: 40.

The composition for reducing skin dullness according to any one of items 23 to 31, further containing a lower alcohol.

The invention further relates to the following method for improving melasma:

item 33. a method for improving melasma comprising applying a purine nucleic acid-related substance to a melasma lesion.

The method for improving melasma according to item 33, wherein the purine nucleic acid-related substance is adenosine monophosphate or a salt thereof.

Item 35 the method for improving melasma according to item 33 or 34, comprising applying a composition containing a purine nucleic acid-related substance to the lesion area of melasma, the purine nucleic acid-related substance being in a ratio of at least 0.01 wt% based on the total amount of the composition.

Item 36. the method for improving melasma according to item 33 or 34, comprising applying a composition containing a purine nucleic acid-related substance to the lesion area of melasma at a ratio of the purine nucleic acid-related substance of 1 to 10 wt% based on the total amount of the composition.

Item 37. the method for improving melasma according to item 35 or 36, wherein the composition has a pH in the range of 2 to 8.

The method for improving melasma according to any one of items 35 to 37, wherein the composition is used as a medicine or quasi-medicine for external application, or a cosmetic.

The method for improving black spot according to any one of items 35 to 38, wherein the composition further comprises a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and an oil, and is formulated into an oil/water-type emulsion.

Item 40. the method for improving black spot according to item 39, wherein the composition further comprises a polyol.

Item 41 the method for improving melasma according to item 39 or 40, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a polymerization degree of 6 or more.

The method for improving melasma according to any one of items 39 to 41, wherein the alkanoyl lactic acid contains an alkanoyl group having 8 or more carbon atoms.

The method for improving black spot according to any one of items 39 to 42, wherein the acrylic acid-alkyl methacrylate copolymer contains C_5-40An alkyl group.

The method for improving melasma according to any one of items 39 to 43, wherein the oil is a hydrocarbon liquid oil.

Item 45 the method for improving melasma according to item 39, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a degree of polymerization of 6 or more, the alkanoyl lactic acid containing an alkanoyl group having 8 or more carbon atoms, the acrylic-methacrylic acid alkyl ester copolymer containing C_5-40Alkyl, and the oil is a hydrocarbon liquid oil.

Item 46 the method for improving black spot according to item 40, wherein the composition contains the polyglycerin fatty acid ester in a ratio of 0.05 to 6% by weight, the alkanoyl lactic acid or the salt thereof in a ratio of 0.01 to 1% by weight, the acrylic acid-alkyl methacrylate copolymer in a ratio of 0.01 to 0.8% by weight, the oil in a ratio of 0.3 to 20% by weight, the polyol in a ratio of 0.05 to 15% by weight, and the water in a ratio of 50 to 90% by weight, based on the total amount of the composition.

Item 47. the method for improving black spot according to any one of items 39 to 46, wherein the composition contains the polyglycerin fatty acid ester and the alkanoyl lactic acid or salt thereof in a weight ratio of 95: 5 to 60: 40.

The method for improving melasma according to any one of items 39 to 47, wherein the composition further comprises a lower alcohol.

The invention further relates to a method for reducing skin dullness, comprising:

the method for alleviating skin dullness, comprising applying a purine nucleic acid-related substance to a skin dullness site.

The method for alleviating skin dullness according to item 49, wherein the purine nucleic acid-related substance is monophosphate or a salt thereof.

Item 51 the method for alleviating dark skin according to item 49 or 50, which comprises applying a composition containing a purine nucleic acid-related substance to a dark skin site, wherein the ratio of the purine nucleic acid-related substance is at least 0.01 wt% based on the total amount of the composition.

Item 52 the method for alleviating skin dullness according to item 49 or 50, which comprises applying a composition containing a purine nucleic acid-related substance to a skin dullness site, the purine nucleic acid-related substance being in a ratio of 1 to 10 wt% based on the total amount of the composition.

The method for reducing skin dullness according to item 51 or 52, wherein the composition has a pH in the range of 2 to 8.

The method for alleviating skin dullness according to any one of items 51 to 53, wherein the composition is used as a medicine or quasi-medicine for external application, or a cosmetic.

Item 55 the method for reducing skin dullness according to any one of items 51 to 54, wherein the composition further contains a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and an oil, and is formulated into an oil/water-type emulsion.

The method for reducing skin dullness according to item 55, wherein the composition further contains a polyhydric alcohol.

The method according to item 55 or 56, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a polymerization degree of 6 or more.

The method for reducing skin dullness according to any one of items 55 to 57, wherein the alkanoyl lactic acid contains an alkanoyl group having 8 or more carbon atoms.

The method for reducing skin dullness according to any one of items 55 to 58, wherein the acrylic acid-alkyl methacrylate copolymer contains C_5-40An alkyl group.

The method for reducing skin dullness according to any one of items 55 to 59, wherein the oil is a hydrocarbon-based liquid oil.

The method for alleviating skin dullness according to any one of items 55 to 60, wherein the polyglycerin fatty acid ester is C_12-36Esters of fatty acids and polyglycerin having a degree of polymerization of 6 or more, the alkanoyl lactic acid containing an alkanoyl group having 8 or more carbon atoms, the acrylic-methacrylic acid alkyl ester copolymer containing C_5-40Alkyl, and the oil is a hydrocarbon liquid oil.

Item 62 the method for reducing skin dullness according to item 56, wherein the composition contains the polyglycerin fatty acid ester in a ratio of 0.05 to 6% by weight, the alkanoyl lactic acid or the salt thereof in a ratio of 0.01 to 1% by weight, the acrylic acid-alkyl methacrylate copolymer in a ratio of 0.01 to 0.8% by weight, the oil in a ratio of 0.3 to 20% by weight, the polyhydric alcohol in a ratio of 0.05 to 15% by weight, and the water in a ratio of 50 to 90% by weight, based on the total amount of the composition.

The method for reducing skin dullness according to any one of items 55 to 62, wherein the composition contains a polyglycerin fatty acid ester and an alkanoyl lactic acid or a salt thereof in a weight ratio of 95: 5 to 60: 40.

The method for reducing skin dullness according to any one of items 55 to 63, wherein the composition further contains a lower alcohol.

The invention also relates to the following embodiments:

item 65 use of a purine nucleic acid related substance for the preparation of a composition for ameliorating melasma.

Item 66. use of a purine nucleic acid-related substance for reducing skin dullness.

Item 67 use of a purine nucleic acid-related substance for ameliorating melasma.

Item 68 use of a purine nucleic acid-related substance for reducing skin dullness.

Brief Description of Drawings

FIG. 1 shows L of a subject prior to administration of a composition^*Value a^*Value b^*Values comparison, L representing skin Brightness 4, 8, 12 and 16 weeks after the start of application^*Mean of difference of values Δ L^*Value a representing skin redness^*Is a difference average Δ a^*B represents skin yellowness^*Difference average of values Δ b^*And a color difference of skin E^*ab change Δ E^*ab。

Best mode for carrying out the invention

(1) Composition for improving melasma

The composition for improving melasma according to the present invention contains a purine nucleic acid-related substance and a pharmaceutically or cosmetically acceptable carrier.

The purine nucleic acid-related substance used in the present invention means one or more purine derivatives or salts thereof having a purine nucleus as a skeleton, and may be referred to as purine bases hereinafter. The purine nucleic acid-related substance that can be used in the present invention is not limited as long as it has an effect of ameliorating melasma when applied to the skin. Any purine nucleic acid related substance that can be incorporated into cosmetics, externally applied medicines, or quasi-medicines can be used without limitation. Water solubility or hydrophilicity is preferred. Examples of purine bases include adenine, guanine, hypoxanthine, xanthine, adenosine, guanosine, inosine, adenosine phosphate [ adenosine 2 '-monophosphate, adenosine 3' -monophosphate, adenosine 5 '-monophosphate (AMP), cyclic adenosine 3' 5 '-monophosphate (cAMP), adenosine 5' -diphosphate (ADP), adenosine 5 '-triphosphate (ATP) ], guanosine phosphate (guanosine 3' -monophosphate, guanosine 5 '-diphosphate, guanosine 5' -triphosphate), adenylic acid succinate, xanthylic acid, inosinic acid, Flavin Adenine Dinucleotide (FAD), nicotinamide purine dinucleotide (NAD), and the like. Preferred among these are adenine, guanine, adenosine monophosphate (adenosine 2 '-monophosphate, adenosine 3' -monophosphate, AMP and cAMP), ADP, ATP, FAD and NAD. The above is preferably adenosine monophosphate, and particularly preferably AMP.

In the present invention, a salt of a purine base may be used instead of the purine base, or a combination of both may be used. Examples of such purine base salts include alkali metal salts such as sodium and potassium salts; alkaline earth metal salts such as calcium salts, magnesium salts and barium salts; salts of basic amino acids such as arginine and lysine; ammonium salts such as ammonium, tricyclohexylammonium salts; and salts of alkanolamines such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine and triisopropanolamine. Alkali metal salts of purine bases are preferred. Particularly preferred are adenosine monophosphate monosodium salt and adenosine monophosphate disodium salt.

The purine nucleic acid-related substance may be used alone, or two or more of them may be used in combination. The manner of combination is not particularly limited as long as the effect of the present invention is not impaired.

Any pharmaceutically or cosmetically acceptable carrier can be used without limitation for the composition for improving melasma of the present invention. Examples of such carriers include water, oil, and the like. The specific examples of such water and oil are the same as those described later for preparing the emulsion composition. Such pharmaceutically or cosmetically acceptable carriers may be used alone or in combination.

The ratio of purine nucleic acid-related substance incorporated in the composition for black spot of the present invention can be determined according to the form of the composition, the target, the desired effect, and the like. More specifically, 0.01 wt% may be used as the lower limit of the ratio for incorporating the purine nucleic acid-related substance, based on the total amount of the composition for improving melasma. In view of the effects of the present invention, the upper limit thereof is not limited and may be within a range suitable for use as a preparation composition. For example, 10 wt% may be used as an upper limit of the ratio for incorporation of the purine nucleic acid-related substance, based on the total amount of the composition. Preferred examples of the ratio for incorporating the purine nucleic acid-related substance include 0.01 to 10% by weight, more preferably 1 to 10% by weight, and particularly preferably 3 to 6% by weight, based on the total amount of the composition. When the ratio is much less than 0.01 wt%, the effect of improving black spot is reduced.

The composition for improving melasma of the present invention may contain, if necessary, various additives typically incorporated into externally applied preparations, such as externally applied medicines or quasi-medicines, or cosmetics. Examples of such additives include surfactants, solubilizing components, emulsifiers, colorants (dyes, pigments), fragrances, preservatives, bactericides, thickeners, antioxidants, chelating agents, pH adjusters, and deodorants. These components may be used alone or in combination of two or more.

The composition for improving melasma of the present invention may further comprise various medicinal agents such as a wetting agent, a UV absorber, a whitening agent, a UV dispersing agent, vitamins, a plant extract, an astringent, an anti-inflammatory agent, a cell activator and the like. These components may be used alone or in combination of two or more.

The composition for ameliorating melasma of the present invention can be formulated into various desired forms such as liquid, oil, lotion, liniment, emulsion, suspension, cream, ointment, tablet, spray, paste and the like.

In particular, the composition for improving melasma of the present invention is preferably formulated into an emulsion composition in an oil/water form such as an emulsion, a cream, and the like, as described below. In the oil/water emulsion composition, the composition for improving melasma of the present invention can be formulated into a stable emulsion form without causing separation, oil floating, and the like, and in addition, the purine nucleic acid-related substance can be effective in improving melasma.

The oil/water emulsion composition may be prepared by mixing: polyglycerol fatty acid ester, alkanoyl lactic acid or its salt, acrylic acid-alkyl methacrylate copolymer, water, and oil by mixing with the above purine nucleic acid related substance and emulsifying.

The polyglycerin fatty acid ester usable in the present invention is not limited. Examples include C_12-36Fatty acid and degree of polymerization of 6 or more, preferably 6-10 esters of polyglycerols. Fatty acids that form esters with polyglycerols include saturated, unsaturated, straight chain and branched chain fatty acids. Specific examples are capric acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, behenic acid, ricinoleic acid and the like.

Specific examples of the polyglycerin fatty acid ester are hexaglycerol monolaurate, hexaglycerol monoisostearate, hexaglycerol monomyristate, hexaglycerol dioleate, hexaglycerol dimyristate, hexaglycerol dipalmitate, hexaglycerol distearate, hexaglycerol dicosanate, hexaglycerol trilaurate, hexaglycerol trimyristate, hexaglycerol tripalmitate, hexaglycerol tristearate, hexaglycerol trilaosanate, hexaglycerol tetralaurate, hexaglycerol tetramyristate, hexaglycerol tetrapalmitate, hexaglycerol tetrastearate, hexaglycerol tetracosanate, hexaglycerol pentalaurate, hexaglycerol pentamyristate, hexaglycerol pentapalmitate, hexaglycerol pentastearate, hexaglycerol pentabehenate, decaglycerol monodecanoate, decaglycerol monolaurate, decaglycerol monomyristate, decaglycerol monopalmitate, decaglycerol monostearate, decaglycerol monooleate, decaglycerol monolinoleate, decaglycerol monoisostearate, decaglycerol didecanoate, decaglycerol dilaurate, decaglycerol dimyristate, decaglycerol dipalmitate, decaglycerol distearate, decaglycerol diisostearate, decaglycerol trilaurate, decaglycerol trimyristate, decaglycerol tripalmitate, decaglycerol tristearate, decaglycerol trioleate, decaglycerol tricosanoate, decaglycerol pentastearate, decaglycerol pentaoleate, decaglycerol pentaisostearate, decaglycerol heptastearate, decaglycerol decastearate, decaglycerol decaoleate, decaglycerol decaisostearate, and the like. However, the polyglycerin fatty acid ester is not limited thereto.

These polyglycerin fatty acid esters may be used alone or in combination. Polyglycerin fatty acid esters having an HLB value of 10 or more, particularly 10 to 15, are suitably used. The polyglycerin fatty acid ester is preferably used in a ratio of 0.05 to 6% by weight, more preferably 0.1 to 5.5% by weight, based on the total amount of the composition for improving melasma.

The alkanoyl lactic acid that can be used in the present invention is not limited. Examples include alkanoyl lactic acids having alkanoyl group with 8 or more carbon atoms, preferably having C_8-18Alkanoyl lactic acid of alkanoyl group. Specific examples include octanoyl lactic acid, hexanoyl lactic acid, 2-ethylhexanoyl lactic acid, lauroyl lactic acid, myristoyl lactic acid, palmitoyl lactic acid, stearoyl lactic acid, isostearoyl lactic acid, oleoyl lactic acid, 12-hydroxystearyl lactic acid, linoleoyl lactic acid, and behenoyl lactic acid. Preferred are stearoyl lactic acid and isostearoyl lactic acid. These alkanoyl lactylates may be used in the form of salts. Examples of such salts include sodium salts, potassium salts, and similar alkali metal salts; ammonium salts, triethanolamine salts, and the like. Preferred are sodium salts, more specifically sodium stearoyl lactylate and sodium isostearoyl lactylate. These alkanoyl lactic acids and salts thereof may be used alone or in combination. The preferable use ratio of the alkanoyl lactic acid or salt thereof is 0.01-1 wt%, and more preferable ratio is 0.1-0.5 wt%, based on the total amount of the composition for improving black spot.

The mixing ratio of the polyglycerin fatty acid ester and the alkanoyl lactic acid or the salt thereof is such that the HLB value of the mixture is 10 or more, preferably 10 to 13. Specific examples of the ratio for mixing the polyglycerin fatty acid ester with the alkanoyl lactic acid or salt thereof are a weight ratio of 95: 5 to 60: 40, preferably 90: 10 to 70: 30.

The acrylic acid-alkyl methacrylate copolymer that can be used in the present invention is not limited. Typical examples generally include copolymers with alkyl chains containing 5 to 40 carbon atoms. Preference is given to copolymers having alkyl chains of from 10 to 30 carbon atoms. Although not so limited, these polymers are commercially available, for example from Novegen Inc. under the trade names Carbopol and Pemulen, such as Carbopol 1342, Pemulen TR-1, and Pemulen TR-2. These acrylic-methacrylic acid alkyl ester copolymers may be used alone or in combination. The acrylic acid-alkyl methacrylate copolymer is preferably used in a ratio of 0.01 to 0.8 wt%, more preferably in a ratio of 0.3 to 0.6 wt%, and still more preferably in a ratio of 0.4 to 0.6 wt%, based on the total amount of the composition for improving black spot.

Any type of water may be used without limitation so long as they are pharmaceutically or cosmetically acceptable. For example, distilled water, ion-exchanged water, sterilized water, or water containing an electrolyte may be used as the water component. Examples of electrolyte-containing water include seawater, hot spring water, mineral water, and the like. The term "seawater" herein refers to surface seawater, intermediate seawater, deep seawater, and ultra-deep seawater. The ratio of water contained in the composition for improving melasma is not limited. Generally, a suitable selection range is 50-90 wt%. A preferred selection range is 60-80 wt%.

The oil that can be used in the present invention is not limited. Specific examples include peanut oil, sesame oil, soybean oil, safflower oil, avocado oil, sunflower oil, corn oil, rapeseed oil, cottonseed oil, castor oil, camellia oil, coconut oil, olive oil, poppy oil, cocoa butter, jojoba oil, and similar vegetable oils; tallow, lard, lanolin, and similar animal oils and fats; petrolatum, liquid paraffin, squalane, α -olefin oligomers, and similar hydrocarbon liquid oils; isopropyl myristate, isopropyl isostearate, myristyl myristate, cetyl palmitate, cetyl isooctanoate, isohexadecyl myristate, n-butyl myristate, octyl dodecyl myristate, isopropyl linoleate, propyl ricinoleate, isopropyl ricinoleate, isobutyl ricinoleate, heptyl ricinoleate, diethyl sebacate, diisopropyl adipate, and similar higher fatty acid esters; white beeswax, spermaceti wax, japan wax, and the like; cetyl alcohol, stearyl alcohol, behenyl alcohol, batyl alcohol, chimyl alcohol, and like higher aliphatic alcohols; a wax; stearic acid, oleic acid, palmitic acid, and similar higher fatty acids; c_12-18Mono of saturated or unsaturated fatty acidsMixtures of di-or triglycerides; methylpolysiloxanes, dimethylpolysiloxanes, methylphenylpolysiloxanes, methylhydropolysiloxanes, and similar linear siloxanes; decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, methylcyclotetrasiloxane, and similar cyclosiloxanes; crosslinked methylpolysiloxanes, crosslinked methylphenylpolysiloxanes, and similar crosslinked silicones; and, silicone oils such as those modified with polyoxyethylene, polyoxypropylene or the like, such as silicone; and others. Preferably, hydrocarbon type liquid oils such as petroleum jelly, liquid paraffin, squalane, and α -olefin polymers are used. These oils may be used alone or in combination. When the oil is a solid, it is preferably liquefied by an auxiliary solvent before use. The oil is preferably used in a ratio of 0.3 to 20 wt%, more preferably 0.5 to 15 wt%, based on the total amount of the composition for improving black spot.

Although the method for preparing the composition for improving melasma, which is in the form of a water/oil emulsion, is not limited, it is preferably prepared according to the following method:

(1) the polyglyceryl fatty acid ester and the alkanoyl lactic acid or salt thereof are mixed with an oil, preferably a polyol. The mixture was heated and stirred. After the mixture was uniformly dissolved, it was cooled to obtain a non-aqueous emulsion.

(2) The thus obtained non-aqueous emulsion is mixed with an aqueous solution (aqueous composition) which is separately prepared and contains the purine nucleic acid-related substance, water, and the acrylic acid-alkyl methacrylate copolymer. The composition in the form of an oil/water emulsion for improving melasma can be obtained according to conventional methods.

The polyhydric alcohol is preferably used in the process (1) for preparing a non-aqueous emulsion to further improve development of emulsification stability of polyglycerin fatty acid ester, alkanoyl lactic acid and the like.

The polyol that can be used herein is not limited. Specific examples include polyglycerols having a polymerization degree of 2 to 10 (e.g., diglycerol, triglycerol, tetraglycerol, etc.), ethylene glycol, diethylene glycol, polyethylene glycol, 1, 3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, pentanediol, sorbitol, maltitol, fructose, and the like. Preferably glycerol is used. These polyols may be used alone or in combination. When used, the polyol is used in a ratio of 0.05 to 15 wt%, preferably 3 to 10 wt%, based on the total amount of the composition.

In the process (2) for emulsification, a lower alcohol may be incorporated in the aqueous solution (aqueous composition) to be mixed with the non-aqueous emulsion, in addition to the electrolyte, water, and the acrylic acid-alkyl methacrylate copolymer. This enhances percutaneous absorption of the purine nucleic acid-related substance. The lower alcohol which can be used in the present invention is not limited, but generally suitable is an alcohol selected from alcohols having 1 to 6 carbon atoms. Preferred examples are ethanol, propanol, isopropanol, and the like_1-4An alcohol. These lower alcohols may be used alone or in combination. Ethanol is preferably used. When used, the lower alcohol is used in a ratio of 0.5 to 15 wt%, preferably 3 to 10 wt%, based on the total amount of the composition for improving black spot.

In addition, a polyhydric alcohol may be used in the aqueous solution (aqueous composition). Such use makes it possible to control the moisturizing ability and sensory characteristics of the composition for improving melasma to a desired degree. Polyols which may be used in the aqueous solution include those identified above. When a polyol is used in preparing the non-aqueous emulsion, it is preferred to use a polyol that is the same as or highly compatible with the polyol used in the aqueous solution.

Examples of the method for emulsifying a mixture of a non-aqueous emulsion and an aqueous solution include stirring the mixture with an emulsifying machine under atmospheric pressure or high pressure. The particles of the formed emulsion may be further refined by a homogenizer, as desired.

The ratio of the non-aqueous emulsion to the aqueous solution (aqueous composition) is not limited. It is generally desirable to control the ratio of the non-aqueous emulsion to 1 to 40% by weight, preferably 1 to 30% by weight, based on the total amount of the composition for improving melasma, thereby obtaining a composition for improving melasma which is present in the form of a more stable oil/water emulsion.

The viscosity of the composition of the present invention in the form of an oil/water emulsion for improving melasma is not limited. The oil/water emulsion composition prepared has a viscosity of 30000cps or less at 20 ℃ which is usually desirable, and is preferably 500-.

The above-described composition for improving melasma according to the present invention, when applied to a melasma-damaged area in the form of an externally applied composition, can produce an effect of improving melasma due to the effect of purine nucleic-related substances contained in the composition. Therefore, the composition for improving melasma of the present invention may be formulated into externally applied compositions, such as externally applied medicines or quasi-medicines, cosmetics, and the like. The purpose of the composition for improving black spot of the present invention is not limited; specific objects include externally administered medications, externally administered quasi-medications; cosmetics such as foundation, blusher, mascara, eye shadow, eyeliner, face powder, lipstick, and the like; basic skin care products such as lotions, creams, lotions, oils and packs; washing products such as face toilet, cleansing cream and body lotion; a cleaning agent; a detergent; bathing agents, and the like.

The composition for improving black spot of the present invention generally has a pH ranging from 2 to 8. In view of irritation to the skin and mucous membrane after use and good skin touch, the pH range is preferably 2 to 7, more preferably 3 to 7, and further more preferably from weakly acidic pH5 to neutral pH 7.

The composition for improving melasma of the present invention can be applied to the melasma lesion area of the skin by adhesion, spraying or direct application, thereby producing the effect of improving melasma. The amount and frequency of use of the composition for improving melasma can be determined depending on the type and concentration of the purine nucleic acid-related substance used, the age, sex, condition of the skin-affected part, application form, expected effect, and the like of the user. The composition for improving melasma of the present invention may be applied to the lesion area of melasma once or several times a day in a suitable amount.

As described above, the purine nucleic acid-related substance has an effect of improving melasma. Thus, the present invention provides the use of a purine nucleic acid-related substance for the manufacture of a composition for ameliorating melasma.

(2) Composition for reducing skin dullness

The composition for reducing skin dullness of the present invention contains a purine nucleic acid-related substance, and a pharmaceutically or cosmetically acceptable carrier.

The composition for reducing skin dullness of the present invention may contain the same purine nucleic acid-related substance as in the above-mentioned composition for improving melasma or may be used as a pharmaceutically or cosmetically acceptable carrier.

The ratio of the purine nucleic acid-related substance incorporated into the composition for alleviating dullness of skin, the wide variety or medicinal properties of additives that can be added to the composition, the form of the composition and its pH are the same as those of the above-mentioned composition for ameliorating melasma.

In particular, it is preferable to formulate the composition for alleviating skin dullness into an emulsion composition such as an emulsion, a cream or the like by mixing and emulsifying a polyglycerin fatty acid ester, an alkanoyl lactic acid or a salt thereof, an acrylic acid-alkyl methacrylate copolymer, water and oil with a purine nucleic acid-related substance. More preferably, the composition is prepared by further mixing a polyol and/or a lower alcohol. The oil/water emulsion composition for reducing skin dullness thus obtained is in a stable emulsified state, does not cause separation and floating of oil, and can effectively exhibit the effect of reducing skin dullness. Types of polyglycerin fatty acid ester, alkanoyl lactic acid or salt thereof, acrylic acid-alkyl methacrylate copolymer, water, oil, polyhydric alcohol and lower alcohol which can be used in the oil/water emulsion composition; the amount thereof; a process for the preparation thereof; and the viscosity thereof, are the same as those of the compositions in the form of oil/water emulsions for improving melasma.

The composition for reducing skin dullness of the present invention can produce the effect of reducing skin dullness by being attached to, sprayed on or directly applied to a skin dullness site. The amount and frequency of use of the composition for improving melasma can be determined depending on the type of purine nucleic-acid-related substance used, its concentration, the age, sex, condition of the skin-affected part, mode of application, desired effect, and the like. The composition for reducing skin dullness of the present invention may be applied to the skin dullness part once or several times a day in a suitable amount.

As described above, the purine nucleic acid-related substance has the effect of reducing skin dullness. Thus, the present invention provides the use of a purine nucleic acid-related substance for the production of a composition for reducing skin dullness.

(3) Method for improving melasma

As described above, the purine nucleic acid-related substance is effective in ameliorating melasma. Thus, the present invention provides a method for improving melasma using a purine nucleic acid-related substance.

The method for improving black spot of the present invention can be carried out by: the purine nucleic acid-related substance itself, or a composition containing the substance, is applied to the melasma lesion.

The purine nucleic acid-related substance which can be used in the method of the present invention is the same as that used in the above composition for improving melasma.

In the method of the present invention, the application manner of the purine nucleic acid-related substance to the melasma lesion is not limited as long as the purine nucleic acid-related substance is brought into contact with the melasma site. For example, a purine nucleic acid-related substance may be applied alone to the lesion area of melasma, or a composition containing the substance as an active ingredient and a pharmaceutically or cosmetically acceptable base, carrier, additive, or pharmaceutical agent may be applied to the lesion area of melasma. More specifically, the substance or the composition containing the substance is applied or sprayed to the targeted skin portion, or is attached to the skin in a sheet form.

A method of applying the composition for improving melasma to the lesion area of melasma may be a preferred embodiment of the present invention.

The amount and frequency of application of the purine nucleic acid-related substance to the lesion area can be determined depending on the type of the purine nucleic acid-related substance used, the age, sex, melasma condition of the user, the mode of application, the intended effect, and the like. The purine nucleic acid-related substance may be applied to the melasma lesion once or several times a day in an appropriate amount.

As described above, melasma can be effectively improved by using a purine nucleic acid-related substance. Therefore, the invention also provides the application of the purine nucleic acid related substance in improving melasma.

(4) Method for reducing skin dullness

As described above, the purine nucleic acid-related substance is effective in reducing skin dullness. Thus, the present invention provides a method for reducing skin dullness using a purine nucleic acid-related substance.

The method for reducing skin dullness of the present invention can be implemented by: the purine nucleic acid-related substance itself, or a composition containing the substance is applied to a skin-dull part.

The purine nucleic acid-related substance in the method of the present invention is the same as that used in the above composition for reducing skin dullness.

In the method of the present invention, the mode of application of the purine nucleic acid-related substance to the skin-dull part is not limited as long as the purine nucleic acid-related substance is brought into contact with the target part. For example, a purine nucleic acid-related substance may be applied alone to a skin-dull part, or a composition containing the substance as an active ingredient and a pharmaceutically or cosmetically acceptable carrier, additive, or medicinal agent may be applied to a skin-dull part. More specifically, the substance or the composition containing the substance is applied or sprayed to the targeted skin portion, or is attached to the skin in a sheet form.

A method of applying a composition for alleviating skin dullness to a skin dullness site may be a preferred embodiment of the present invention.

The amount and frequency of application of the purine nucleic acid-related substance to the skin dark site can be determined depending on the type of the purine nucleic acid-related substance used, the age, sex, intended use, dark site condition, application mode, and the like. The purine nucleic acid-related substance may be applied to the skin-dull part once or several times a day in a suitable amount.

As described above, by using the purine nucleic acid-related substance, skin dullness can be effectively reduced. Thus, the present invention also provides the use of a purine nucleic acid-related substance for reducing skin dullness.

Examples

The present invention is described in more detail by referring to the following examples, although the present invention is not limited to these examples.

Example 1Emulsion liquid

(wt％)

Adenosine 5' -disodium monophosphate 3.0

Sodium isostearyl lactate 0.2

Acrylic acid-alkyl methacrylate copolymer 0.4

Light liquid paraffin 5.0

Glycerol 6.0

Ethanol 5.0

Proper amount of preservative

Decaglycerol monoisostearate 1.5

Decaglycerol monomyristate 0.3

PH regulator (pH6.5)

Pure water balance

100.0wt％

According to the above formulation, an emulsion was produced by the method described below. Decaglycerol monoisostearate, decaglycerol monomyristate, sodium isostearoyl lactate, glycerol, and light liquid paraffin were mixed, heated to dissolve, and then cooled to prepare a homogeneous nonaqueous emulsion. An aqueous composition (aqueous solution) prepared separately by dissolving adenosine 5' -disodium monophosphate, acrylic acid-alkyl methacrylate copolymer, ethanol, a preservative and a pH adjuster in distilled water (pure water) is mixed with a non-aqueous emulsion. The mixture was stirred by an emulsifier to be an emulsion in an oil/water emulsified state.

Test example 1Improvement test for black spot

The inventors conducted the following test to evaluate the effect of the purine nucleic acid-related substance on improving melasma.

< test method >

The emulsion prepared according to the formulation of example 1 was applied to the entire face of 27 patients with black spots in an appropriate amount (amount uniformly applied to the entire face: approximately five drops), twice daily, after washing the face for 16 weeks (except for a 12 week end). The color intensity and degree of melasma were evaluated collectively by the dermatologist before and after 4, 8, 12 and 16 weeks from the start of application, and the melasma status of each patient was classified into five grades, "no melasma", "slight", "mild", "moderate" and "severe" according to the criteria as in table 1 below.

TABLE 1

Symptoms and signs		Degree of
							Is free of	Ultra-limited	Limited by	Of moderate degree	Is extensive in application
		Intensity of color	Is free of	Is free of	Is free of	Is free of						Is free of	Is free of
Slight faint color	Is free of						Light and slight	Light and slight	Mild degree of	Of moderate degree
			Weak colour	Is free of	Light and slight	Mild degree of					Of moderate degree	Of moderate degree
Of moderate degree	Is free of						Light and slight	Of moderate degree	Severe severity of disease	Severe severity of disease
			High strength	Is free of	Of moderate degree	Of moderate degree					Severe severity of disease	Severe severity of disease

Before and after the application, the grades of melasma of the patients diagnosed by the dermatologist were compared to evaluate the degree of improvement of melasma according to the following criteria.

Evaluation criteria for degree of improvement in black spot

Cure all symptoms disappear

Improvement according to the criteria of Table 1, two levels or better improvement can be achieved

Slight improvement according to the criteria of Table 1, less than two levels of improvement were observed

No change or deterioration and no improvement

Test results

The results obtained are shown in Table 2. Table 2 shows the number of patients meeting the above evaluation criteria for the improvement level of melasma, the ratio of the effect of "slight improvement" or better (the ratio (%) of patients showing "slight improvement" or better effect), and the 95% confidence interval of the percentage of patients having "slight improvement" or better effect, 4, 8, 12 and 16 weeks after the start of administration.

TABLE 2

	Degree of improvement of black spot (number of patients)				Slightly improved or better effect ratio (%)	95% confidence interval
								Cure of disease	Improvements in or relating to	Slight improvement	Without change or deterioration
4 weeks after initiation of external application	0	0	5	22	18.5	6.3-38.1
							8 weeks after initiation of external application	0	5	10	12	55.6	35.3-74.5
12 weeks after initiation of external application	0	10	10	7	74.1	53.7-88.9
							16 weeks after initiation of external application	0	10	14	2	92.3	74.9-99.1

As is apparent from table 2, by using the emulsion containing AMP2Na, a significant melasma-improving effect was exhibited. More specifically, 74.1% of the patients showed improvement in melasma 12 weeks after the start of external application, and 92.3% of the patients showed improvement in melasma 16 weeks after the start of application, and the statistical improvement effect of melasma was considered to be significant.

The above test results show that the substance related to purine nucleic acids exhibits an excellent melasma-improving effect when applied to the melasma lesion, and thus the substance is considered to be useful for improving melasma.

Test example 2Test for reducing skin dullness

The inventors conducted the following test to evaluate the skin dullness-reducing effect of purine nucleic acid-related substances.

Test method

The emulsion prepared according to the formulation of example 1 was applied in a suitable amount (amount uniformly applied to the whole face: about five drops) to the whole face of 27 dull-skinned women twice a day for 16 weeks after washing the face. The skin color tone of the subject was measured with a color difference meter (OFC-300A, Nippon Denshoku industries co., Ltd.) before the start of application and after 4, 8, 12 and 16 weeks from the start of application. L representing skin brightness by measuring evaluation target area of each patient^*Value, a representing skin redness^*A value, and b representing skin yellow^*Values were obtained to obtain measured values, each value was measured 11 times, two maximum values and two minimum values were removed, and an average of 7 measured values was calculated.

Test results

The results obtained are shown in FIG. 1. FIG. 1 shows L of a subject prior to administration of a composition^*Value a^*Value b^*Values are compared and L, which indicates skin brightness, 4, 8, 12 and 16 weeks after the start of application^*Mean of difference of values Δ L^*The value "a" of skin redness^*Is a difference average Δ a^*And a color difference of skin E^*ab change Δ E^*ab。ΔE^*The ab value is calculated by equation 1.

Formula 1

ΔE^*ab＝[(ΔL^*)²+(Δa^*)²+(Δb^*)²]^1/2

L on skin 4 weeks after the start of application by applying an emulsion containing AMP2Na to the skin^*Value (skin lightness)) A significant increase, whereas b indicates yellowness 4 weeks after the start of administration^*The value is significantly reduced. 8 weeks after the start of administration, refer to degree of redness a^*The values began to increase, whereas the increase was more pronounced 12 weeks after the start of administration. A denotes degree of redness^*The trend of the values indicates that the change in skin redness is not caused by the instantaneous improvement in blood flow. It is known that Δ E as a color difference change display index^≠ab values indicate the total change in lightness, redness and yellowness in the skin, which can generally be observed subjectively and objectively when the delta value reaches a value of 2 or higher. Due to Delta E4 weeks after the start of administration^≠ab values already above 2, it can be assumed that the skin tone has changed significantly.

The above test results show that the purine nucleic acid-related substance exhibits an excellent skin dullness reducing effect when applied to a skin dullness site, and thus the substance is considered to be useful for reducing skin dullness.

Test example 3Emulsion stability test of the composition in oil/water emulsified state for ameliorating melasma or reducing dullness of the skin:

the inventors carried out the following tests to evaluate the stability of the emulsion of the composition in the oil/water emulsified state for improving melasma or reducing dullness of the skin.

Test method

In order to evaluate the emulsion stability test of the composition in an oil/water emulsified state for the improvement of melasma or the reduction of skin dullness, a composition for the improvement of melasma or the reduction of skin dullness was prepared according to the formulation shown in table 3. First, a polyglycerin fatty acid ester, an alkanoyl lactate, an oil and a polyhydric alcohol are mixed, dissolved by heating, and then cooled to prepare a uniform non-aqueous emulsion. An aqueous composition (aqueous solution) prepared separately by dissolving an electrolyte, an acrylic acid-alkyl methacrylate copolymer, a polyhydric alcohol, a lower alcohol, a pH adjuster, and a preservative in distilled water (pure water) is mixed with a non-aqueous emulsion. The mixture was stirred by an emulsifying machine to obtain a composition in an oil/water emulsified state for improving melasma or reducing dullness of the skin (examples 2 to 5). For comparison, a composition for improving melasma which does not contain alkanoyl lactate (comparative example 1) and a composition for reducing skin dullness which does not contain an acrylic acid-alkyl methacrylate copolymer (comparative example 2) were prepared in the same manner as in examples 2 to 5 (Table 4 shows ingredients for these emulsion compositions).

Each of the ten compositions (examples 2 to 5 and comparative examples 1 and 2) thus prepared for improving melasma or for reducing dullness of skin was placed in two transparent glass bottles. One bottle was stored at 60 ℃ for 2 weeks and the other bottle was subjected to 14 cycles (24 hours per cycle) at a temperature ranging from-5 ℃ to 40 ℃. After the test, the appearance (separation, floating of oil, presence or absence of gel formation) of each emulsion composition was visually observed and evaluated according to the following criteria.

< evaluation criteria >

A: neither separation, floating of oil nor gel formation was observed

B: separation, oil floating or gel formation was observed.

TABLE 3

		Example 2	Example 3	Example 4	Example 5
						1	Decaglycerol monoisostearate	-	1.6	0.16	4.8
2	Decaglycerol diisostearate	1.2	-	-	-
						3	Decaglycerol monostearate	-	-	0.02	0.5

4	Decaglycerol monomyristate	0.6	0.2	-	-
						5	Sodium stearoyl lactylate	-	-	0.02	-
6	Sodium isostearyl lactylate	0.2	0.2	-	0.5
						7	Squalane	5.0	8.0	-	15.0
8	Alpha-olefin oligomer	-	-	5.0	-
						9	Pure glycerin	6.0	6.0	2.0	9.0
10	Dipropylene glycol	-	-	5.0	-
						11	Adenosine monophosphate disodium salt	1.5	1.5	3.0	6.0
12	Acrylic acid-alkyl methacrylate copolymer	0.4	0.5	0.5	0.5
						13	Ethanol	5.0	5.0	3.0	3.0
14	pH regulator	Proper amount of	Proper amount of	Proper amount of	Proper amount of
						15	Preservative	Proper amount of	Proper amount of	Proper amount of	Proper amount of
16	Pure water	Balance of	Balance of	Balance of	Balance of
						Viscosity (cps)20 deg.C		4200	17000	1400	1100
Long term stability (60 ℃ 2 weeks)		A	A	A	A
						Long term stability (-5-40 ℃ cycle: 2 weeks)		A	A	A	A

TABLE 4

		Comparative example 1	Comparative example 2
				1	Decaglycerol monoisostearate	2.0	-
2	Decaglycerol diisostearate	-	1.2
				3	Decaglycerol monomyristate	-	0.6
4	Sodium isostearyl lactylate	-	0.2
				5	Squalane	5.0	-
6	Alpha-olefin oligomer	-	5.0
				7	Pure glycerin	6.0	8.0
8	Carboxylic acid polymers	-	0.6
				9	Adenosine monophosphate disodium salt	3.0	3.0
10	Acrylic acid-alkyl methacrylate copolymer	0.5	-
				11	Ethanol	3.0	5.0
12	pH regulator	Proper amount of	Proper amount of
				13	Preservative	Proper amount of	Proper amount of
14	Pure water	Balance of	Balance of
				Viscosity (cps)20 deg.C		2,000	1,200
Long term stability (60 ℃ 2 weeks)		A	B
				Long term stability (-5-40 ℃ cycle: 2 weeks)		B	A

Test results

Tables 3 and 4 show the emulsion stability test results of the compositions for improving melasma of examples 2-5, and the compositions of comparative examples 1 and 2.

As can be seen from tables 3 and 4, the compositions in the oil/water emulsified state for improving melasma or reducing skin dullness of examples 2 to 5 inhibited water/oil phase separation, oil floating and gel formation, and stably maintained their emulsified state even when they contained a relatively large amount of AMP2Na under conditions in which the emulsion compositions were highly likely to be affected by long-term storage and temperature changes. In contrast, as shown in comparative example, the emulsion composition in the oil/water emulsified state without acrylic acid-alkyl methacrylate copolymer (comparative example 2) lacks long-term emulsion stability, while the emulsion composition without alkanoyl lactate (comparative example 1) forms gel with temperature change, thereby failing to maintain a stable emulsified state.

As is apparent from the above, when formulated into the oil/water emulsion composition as described above, a composition for ameliorating melasma or reducing dullness of skin in the form of an emulsion or cream can be provided in a stable manner.

Industrial applicability

When the composition for improving melasma of the present invention is applied to a melasma lesion, an excellent melasma improving effect is exhibited due to the action of purine nucleic acid-related substances.

When the composition for reducing skin dullness of the present invention is applied to a skin dullness part, an excellent skin dullness reducing effect is exhibited due to the action of the purine nucleic acid-related substance.

Purine nucleic acid-related substances contained in a composition for ameliorating melasma or reducing skin dullness as active ingredients are highly safe to the human body because they are inherently present in the living body. Thus, the substance can be applied to cosmetics in addition to externally applied medicines or quasi-medicines. Thus, the present invention provides a means for improving melasma or dullness of the skin by daily use of a cosmetic containing the same, thereby being easily applied to a patient.

Further, the composition for ameliorating melasma or reducing skin dullness in the oil/water emulsified state of the present invention has good emulsion stability in addition to the excellent effect of ameliorating melasma or reducing skin dullness, and thus can be used as an external application agent for skin in the form of a cream or emulsion.

The method for improving black spot disease of the present invention can effectively improve black spot disease.

The method for reducing skin dullness of the present invention can effectively reduce skin dullness.

Claims (9)

1. Composition for ameliorating melasma or reducing skin dullness, comprising adenosine monophosphate or salt thereof, C_12-36Polyglycerol fatty acid ester comprising fatty acid and polyglycerol with polymerization degree of 9-10, alkanoyl lactic acid having C8-18 alkanoyl group or its salt, and C-containing polysaccharide_5-40Alkyl chain acrylic acid-alkyl methacrylate copolymer, water and oil, and preparing into oil/water-type emulsion, wherein the polyglycerol fatty acid ester is 0.05-6 wt% and the alkanoyl lactic acid or its salt is 0.01-1 wt% based on the total composition, and the acrylic acid-alkyl methacrylate copolymer is contained0.01-0.8 wt%, oil content 0.3-20 wt%, and water content 50-90 wt%.

2. The composition for ameliorating melasma or reducing skin dullness according to claim 1, wherein the adenosine monophosphate is adenosine 5' -monophosphate.

3. The composition for ameliorating melasma or reducing skin dullness according to claim 1, comprising at least 0.01% by weight of adenosine monophosphate or a salt thereof based on the total amount of the composition.

4. The composition for improving melasma or reducing skin dullness according to claim 1, which contains adenosine monophosphate or a salt thereof in an amount of 1 to 10% by weight based on the total amount of the composition.

5. The composition for ameliorating melasma or reducing skin dullness according to claim 1, further comprising a polyhydric alcohol selected from the group consisting of glycerin, polyglycerin having a polymerization degree of 2 to 10, ethylene glycol, diethylene glycol, polyethylene glycol, 1, 3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, pentanediol, sorbitol, maltitol and fructose, in a polyhydric alcohol ratio of 0.05 to 15% by weight.

6. The composition for improving melasma or reducing skin dullness according to claim 1, wherein the weight ratio of the polyglycerol fatty acid ester to the alkanoyl lactic acid or salt thereof is 95: 5 to 60: 40.

7. The composition for ameliorating melasma or reducing skin dullness according to claim 1, further comprising a lower alcohol having 1 to 6 carbon atoms, the lower alcohol being used at a ratio of 0.5% to 15% by weight based on the total amount of the composition.

8. Use of adenosine monophosphate or a salt thereof for preparing a composition for improving melasma comprising C_12-36Polyglycerol fatty acid ester comprising fatty acid and polyglycerol with polymerization degree of 9-10, alkanoyl lactic acid having C8-18 alkanoyl group or its salt, and C-containing polysaccharide_5-40An alkyl chain acrylic acid-alkyl methacrylate copolymer, water and an oil, and formulated into an oil/water-type emulsion containing 0.05 to 6 wt% of a polyglycerin fatty acid ester, 0.01 to 1 wt% of an alkanoyl lactic acid or a salt thereof, 0.01 to 0.8 wt% of an acrylic acid-alkyl methacrylate copolymer, 0.3 to 20 wt% of an oil, and 50 to 90 wt% of water, based on the total amount of the composition.

9. Use of adenosine monophosphate or a salt thereof for preparing a composition for reducing skin dullness, the composition comprising C_12-36Polyglycerol fatty acid ester comprising fatty acid and polyglycerol with polymerization degree of 9-10, alkanoyl lactic acid having C8-18 alkanoyl group or its salt, and C-containing polysaccharide_5-40An alkyl chain acrylic acid-alkyl methacrylate copolymer, water and an oil, and formulated into an oil/water-type emulsion containing 0.05 to 6 wt% of a polyglycerin fatty acid ester, 0.01 to 1 wt% of an alkanoyl lactic acid or a salt thereof, 0.01 to 0.8 wt% of an acrylic acid-alkyl methacrylate copolymer, 0.3 to 20 wt% of an oil, and 50 to 90 wt% of water, based on the total amount of the composition.