Topical composition

Abstract

To provide a topical composition that promotes the skin penetration of a water-soluble active ingredient and prevents the occurrence of phase separation.SOLUTION: A topical composition contains (A) a water-soluble active ingredient, (B) a polyglyceryl fatty acid ester, and (C) a polyol.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to a composition for external use that enhances the penetration of a water-soluble active ingredient into the skin and is less susceptible to phase separation. [Background technology]

[0002] The skin is composed of the epidermis, dermis, and subcutaneous tissue from the surface of the body, and the epidermis has a barrier function to prevent the intrusion of foreign substances and the evaporation of water. The epidermis is composed of four layers, the stratum corneum, the granular layer, the spinous layer, and the basal layer, of which the stratum corneum is hydrophobic. Many of the active ingredients incorporated in external compositions for preventing and improving rough skin, age spots, wrinkles, etc. are water-soluble, but water-soluble active ingredients have a disadvantage that they are difficult to diffuse throughout the epidermis due to their low permeability into the stratum corneum. Therefore, in order to fully exert the effects of water-soluble active ingredients, a formulation technology that increases the permeability of the water-soluble active ingredients into the skin is desired.

[0003] Various techniques for enhancing the permeability of water-soluble active ingredients into the skin have been studied. For example, Patent Document 1 describes that a diester of a specific dicarboxylic acid and a specific polyoxyethylene monoalkyl ether can be used as a permeation enhancer for active ingredients. Patent Document 2 also describes that (A) a water-soluble active ingredient, (B) a distance Ra between the Hansen solubility parameter value of the target site is 8 (MPa) 1 / 2 or less, and the hydrogen bond term δH is 3.5 (MPa) 1 / 2 It is described that the penetration of a water-soluble active ingredient into the skin can be promoted by mixing the above oil, (C) a surfactant, and (D) water and solubilizing the resulting mixture. Patent Document 3 describes that the use of a vesicle having a membrane comprising (A) acylproline or a salt thereof, and (B) an amphiphilic substance can enhance the permeability of an active ingredient with low affinity to the skin. Patent Document 4 describes that the transdermal delivery of tranexamic acid, a water-soluble active ingredient, can be enhanced by contacting the skin with a composition having a pH of 3.5 to 6.5 containing tranexamic acid, and then subjecting the skin to iontophoresis from the positive electrode side. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2009-35497 A [Patent Document 2] Patent Publication No. 2022-70845 [Patent Document 3] JP 2018-203660 A [Patent Document 4] JP 2006-298850 A Summary of the Invention [Problem to be solved by the invention]

[0005] Conventionally reported formulation techniques for promoting the penetration of water-soluble active ingredients into the skin have insufficient skin penetration or limitations in formulation, so the development of new formulation techniques is desired. Conventionally, hydrogenated lecithin has been known to have the effect of promoting the penetration of water-soluble active ingredients into the skin, and a simple composition containing a water-soluble active ingredient and hydrogenated lecithin can promote the penetration of the water-soluble active ingredient into the skin, but a topical composition containing a water-soluble active ingredient and hydrogenated lecithin has the disadvantage that phase separation is likely to occur during storage and storage stability is low.

[0006] Therefore, an object of the present disclosure is to provide a composition for external use that promotes the penetration of a water-soluble active ingredient into the skin and is less likely to cause phase separation. [Means for solving the problem]

[0007] The present inventors have conducted intensive research to solve the above problems, and have found that by incorporating a water-soluble active ingredient, a polyglycerol fatty acid ester, and a polyol in a topical composition, the penetration of the water-soluble active ingredient into the skin can be promoted, and phase separation is unlikely to occur, resulting in good storage stability. The present disclosure has been completed based on this knowledge and through further research.

[0008] That is, the present disclosure provides the inventions of the following aspects. Item 1. A composition for external use comprising (A) a water-soluble active ingredient, (B) a polyglycerol fatty acid ester, and (C) a polyol. Item 2. The composition for external use according to Item 1, further comprising (D) a dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester. Item 3. The composition for external use according to Item 1 or 2, further comprising (E) a liquid fatty acid. Item 4. The composition for external use according to any one of Items 1 to 3, wherein the (A) water-soluble active ingredient is at least one selected from the group consisting of tranexamic acid, arbutin, ascorbic acid, a salt of ascorbic acid, an ascorbic acid derivative, nicotinic acid, and a nicotinic acid derivative. Item 5. The composition for external use according to any one of Items 1 to 4, wherein the water-soluble active ingredient (A) is tranexamic acid. Item 6. The composition for external use according to any one of Items 1 to 5, wherein the (B) polyglycerol fatty acid ester is at least one selected from the group consisting of polyglyceryl monolaurate, polyglyceryl diisostearate, polyglyceryl monocaprate, polyglyceryl monocaprylate, polyglyceryl dilaurate, polyglyceryl trilaurate, polyglyceryl myristate, polyglyceryl dimyristate, polyglyceryl trimyristate, polyglyceryl monooleate, polyglyceryl dioleate, polyglyceryl trioleate, polyglyceryl monostearate, polyglyceryl distearate, polyglyceryl tristearate, polyglyceryl monoisostearate, polyglyceryl (eicosadioate / tetradecanedioate), polyglyceryl (isostearate / succinate), and polyglyceryl penta(behenate / eicosadioate). Item 7. The composition for external use according to any one of Items 1 to 6, wherein the polyglycerol fatty acid ester (B) has an HLB value of 10 or more. Item 8. The composition for external use according to any one of Items 1 to 7, wherein the (B) polyglycerol fatty acid ester is polyglyceryl monolaurate and / or polyglyceryl diisostearate. Item 9. The composition for external use according to any one of Items 1 to 8, wherein the polyol (C) is glycerin. Item 10. The composition for external use according to Item 2, wherein the (D) dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester is cyclohexane-1,4-dicarboxylate bisethoxydiglycol. Item 11. The composition for external use according to Item 3, wherein the (E) liquid fatty acid is isostearic acid. Item 12. Use of a composition containing (A) a water-soluble active ingredient, (B) a polyglycerol fatty acid ester, and (C) a polyol for producing a composition for external use. Effect of the Invention

[0009] According to the present disclosure, a composition for external use is provided which can promote the penetration of a water-soluble active ingredient into the skin, is less likely to cause phase separation, and has excellent storage stability. In addition, in one embodiment of the composition for external use of the present disclosure, the ingredients are easily dispersed uniformly, so that the ingredients can be dispersed uniformly by a simple stirring operation during production, which is advantageous in that production efficiency is improved. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] In this document, the description of a numerical range "X to Y" refers to a numerical range from X to Y inclusive.

[0011] The topical composition of the present disclosure is characterized by containing (A) a water-soluble active ingredient, (B) a polyglycerol fatty acid ester, and (C) a polyol. The topical composition of the present disclosure will be described in detail below.

[0012] [(A) Water-soluble active ingredient] The topical composition of the present disclosure contains a water-soluble active ingredient (sometimes simply referred to as "ingredient (A)"). The topical composition of the present disclosure contains a polyglycerol fatty acid ester and a polyol, which will be described later, and thereby can promote the penetration of the water-soluble active ingredient into the skin and can also suppress phase separation during storage.

[0013] In this disclosure, a water-soluble active ingredient is an active ingredient that is "slightly soluble," "easily soluble," or "extremely soluble" in water according to the definition set forth in the 19th Revised Edition of the Japanese Pharmacopoeia, and specifically refers to an active ingredient that requires less than 30 mL of water to dissolve 1 g of the active ingredient within 30 minutes when the active ingredient is placed in water and vigorously shaken every 5 minutes at 20±5°C.

[0014] The type of water-soluble active ingredient is not particularly limited, as long as it is water-soluble and effective on the epidermis or dermis. Examples of water-soluble active ingredients include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, wheat protein, wheat proteolytic peptides, hydrolyzed wheat protein, casein hydrolyzed peptides, and other proteins, hydrolysates thereof, and derivatives thereof; acylated peptides such as palmitoyl oligopeptide, palmitoyl pentapeptide, and palmitoyl tetrapeptide; betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, tyrosine, β-alanine, threonine, glutamic acid, glutamine, asparagine, asparagine, and the like. Amino acids such as paragic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, tryptophan, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine, their salts, and their derivatives; 18-methyleicosanoic acid salts, branched fatty acid (12-31) salts, lanolin fatty acid salts, ethyl sulfate 18-methyleicosanoic acid aminopropylethyldimethylammonium, ethyl sulfate long-chain branched fatty acid (12-31) aminopropylethyldimethylammonium 18-methyleicosanoic acid and anteiso fatty acid derivatives such as ethyl lanolin sulfate fatty acid aminopropylethyldimethylammonium; water-soluble sphingolipids such as sugar ceramide; vitamin C such as ascorbic acid and its sodium salts; ascorbic acid derivatives such as ascorbic acid ethyl ether, ascorbic acid-2-glucoside, ascorbic acid phosphate sodium salt, ascorbic acid phosphate magnesium salt, palmitoyl ascorbic acid phosphate sodium salt, and tocopheryl ascorbyl phosphate;Thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, flavin adenine dinucleotide, cyanocobalamin, folic acids, nicotinic acid, nicotinic acid derivatives (nicotinamide, etc.) and other nicotinic acids, choline and other vitamin Bs; other vitamins such as pantothenic acid, panthenyl ethyl ether, panthenol, biotin; water-soluble vitamin E such as tocopherol phosphate; hydroquinone glycosides such as arbutin and α-arbutin, and the like. esters of; kojic acid, ellagic acid salts, tranexamic acid and its derivatives, ferulate salts and its derivatives, placenta extract, glutathione, glycyrrhizic acid, glycyrrhizic acid salts and glycyrrhizin derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, caffeine, α-lipoic acid, rutin and glycoside derivatives, hesperidin and glycoside derivatives, and various plant extracts such as Nishikawa willow extract.

[0015] These water-soluble active ingredients may be used alone or in combination of two or more.

[0016] Among these water-soluble active ingredients, suitable examples include water-soluble active ingredients having a molecular weight of not more than 400. Specific examples of water-soluble active ingredients having a molecular weight of not more than 400 include tranexamic acid, arbutin, ascorbic acid, salts of ascorbic acid, ascorbic acid derivatives, nicotinic acid, and nicotinic acid derivatives.

[0017] Among the water-soluble active ingredients, tranexamic acid is preferable from the viewpoint of further improving the effect of promoting skin penetration and the effect of suppressing phase separation.

[0018] In the topical composition of the present disclosure, the content of the water-soluble active ingredient may be appropriately set depending on the water solubility and type of active ingredient used, the dosage form and use of the topical composition, etc., and may be, for example, 0.01 to 15 wt. % of the total amount of the water-soluble active ingredient, preferably 0.05 to 5 wt. %, and more preferably 0.1 to 5 wt. %.

[0019] [(B) Polyglycerol fatty acid ester] The topical composition of the present disclosure further contains a polyglycerol fatty acid ester (sometimes simply referred to as "component (B)"). In the topical composition of the present disclosure, the polyglycerol fatty acid ester, when used in combination with a polyol described below, promotes the penetration of the water-soluble active ingredient into the skin and also exhibits the effect of suppressing phase separation during storage.

[0020] The polyglycerol fatty acid ester is an ester of a fatty acid and polyglycerol.

[0021] In the polyglycerol fatty acid ester, the number of ester bonds (the number of fatty acids bonded per one polyglycerol molecule) is, for example, 1 to 10, preferably 1 to 5, more preferably 1 to 3, and even more preferably 1 or 2.

[0022] The number of carbon atoms of the fatty acid constituting the polyglycerol fatty acid ester is, for example, 8 to 30, preferably 12 to 22, and more preferably 12 to 18. The fatty acid constituting the polyglycerol fatty acid ester may be either linear or branched, and may be either saturated or unsaturated.

[0023] The degree of polymerization of the polyglycerin constituting the polyglycerin fatty acid ester (the number of glycerin bonds) is, for example, 2-20, preferably 4-16, and more preferably 6-10.

[0024] Specific examples of polyglycerol fatty acid esters include polyglyceryl monocaprate, polyglyceryl monocaprylate, polyglyceryl monolaurate, polyglyceryl dilaurate, polyglyceryl trilaurate, polyglyceryl myristate, polyglyceryl dimyristate, polyglyceryl trimyristate, polyglyceryl monooleate, polyglyceryl dioleate, polyglyceryl trioleate, polyglyceryl monostearate, polyglyceryl distearate, polyglyceryl tristearate, polyglyceryl monoisostearate, polyglyceryl diisostearate, polyglyceryl (eicosane diacid / tetradecanedioic acid), polyglyceryl (isostearate / succinic acid), and polyglyceryl penta(behenic acid / eicosane diacid).

[0025] These polyglycerol fatty acid esters may be used alone or in combination of two or more.

[0026] Among these polyglycerol fatty acid esters, preferred examples include polyglycerol fatty acid esters having an HLB value of at least 10. In the present disclosure, the HLB value is a value calculated by the Griffin method.

[0027] From the viewpoint of further improving the effect of promoting skin penetration and the effect of inhibiting phase separation, among the polyglycerol fatty acid esters, preferred are polyglyceryl monolaurate, polyglyceryl diisostearate, polyglyceryl monomyristate, and polyglyceryl (eicosane diacid / tetradecanedioate); more preferred are polyglyceryl-10 laurate (decaglyceryl monolaurate), polyglyceryl-10 diisostearate (decaglyceryl diisostearate), polyglyceryl-10 myristate (decaglyceryl monomyristate), polyglyceryl-10 (eicosane diacid / tetradecanedioate) (decaglyceryl (eicosane diacid / tetradecanedioate)); and even more preferred are polyglyceryl-10 laurate and polyglyceryl-10 sostearate.

[0028] In the topical composition of the present disclosure, the content of the polyglycerol fatty acid ester is, for example, 0.0001 to 2 wt %, preferably 0.01 to 1 wt %, and more preferably 0.1 to 0.5 wt %, in terms of the total amount of the polyglycerol fatty acid ester.

[0029] [(C) Polyol] The topical composition of the present disclosure further contains a polyol (sometimes simply referred to as "component (C)"). In the topical composition of the present disclosure, the combination of a polyglycerol fatty acid ester and a polyol can promote the penetration of the water-soluble active ingredient into the skin and further suppress phase separation during storage.

[0030] Polyol is a compound having two or more hydroxyl groups. The type of polyol is not particularly limited, but examples thereof include dihydric alcohols such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, isoprene glycol, hexylene glycol, and 1,3-butylene glycol; trihydric alcohols such as glycerin and trimethylpropanol; tetrahydric or higher alcohols such as diglycerin, triglycerin, tetraglycerin, hexaglycerin, decaglycerin, and trimethylpropanol; and sugars or sugar alcohols such as erythritol, pentaerythritol, dipentaerythritol, glucose, mannose, galactose, sucrose, fructose, maltose, trehalose, maltitol, xylitol, inositol, sorbitan, and sorbitol.

[0031] These polyols may be used alone or in combination of two or more.

[0032] Among these polyols, from the viewpoint of further improving the effect of promoting skin penetration and the effect of suppressing phase separation, preferred are dihydric alcohols and trihydric alcohols; more preferred are lower dihydric alcohols (dihydric alcohols having 2 to 5 carbon atoms) and trihydric alcohols; even more preferred are 1,3-butylene glycol and glycerin; and particularly preferred is glycerin.

[0033] In the topical composition of the present disclosure, the content of the polyol is, for example, 0.01 to 30 wt %, preferably 0.5 to 10 wt %, and more preferably 1 to 8 wt %, in terms of the total amount of polyol.

[0034] [(D) Dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester] The topical composition of the present disclosure may contain, in addition to the components (A) to (C), a dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester (sometimes referred to as component (D)).

[0035] The dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester is a diester compound of a dicarboxylic acid and a polyoxyalkylene alkyl ether.

[0036] The number of carbon atoms of the dicarboxylic acid constituting the dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester is, for example, 2 to 18, preferably 4 to 16, and more preferably 6 to 10. The dicarboxylic acid may have either a chain or a cyclic structure. Specific examples of the dicarboxylic acid include oxalic acid, malonic acid, succinic acid, tartaric acid, malic acid, glutaric acid, adipic acid, pemelic acid, suberic acid, azelaic acid, sebacic acid, aspartic acid, glutamic acid, acetone dicarboxylic acid, phthalic acid, and cyclohexane-1,4-dicarboxylic acid.

[0037] In the polyoxyalkylene alkyl ether constituting the dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester, examples of the polyoxyalkylene chain include polyoxyethylene and polyoxypropylene. The number of moles of alkylene oxide added to the polyoxyalkylene chain is 2 to 8, preferably 2 to 6, more preferably 2 to 4, and even more preferably 2 or 3. In the polyoxyalkylene alkyl ether constituting the dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester, the number of carbon atoms in the alkyl group is, for example, 1 to 8, preferably 1 to 6, more preferably 1 to 4, and even more preferably 2. Specific examples of the polyoxyalkylene alkyl ether include diethylene glycol monoethyl ether and triethylene glycol monoethyl ether.

[0038] The dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester may be used alone or in combination of two or more kinds.

[0039] Among the dicarboxylate bis(polyoxyalkylene alkyl ether) esters, from the viewpoint of further improving the effect of promoting skin penetration and the effect of suppressing phase separation, preferred are bisethoxydiglycol cyclohexane-1,4-dicarboxylate (a diester compound of cyclohexane-1,4-dicarboxylic acid and diethylene glycol monoethyl ether) and bisethoxydiglycol succinate (a diester compound of succinic acid and diethylene glycol monoethyl ether); and more preferred are bisethoxydiglycol cyclohexane-1,4-dicarboxylate.

[0040] When the topical composition of the present disclosure contains a dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester, the content thereof is, for example, 0.01 to 2 wt %, preferably 0.5 to 1.5 wt %, and more preferably 0.1 to 1 wt %.

[0041] [(E) Liquid fatty acid] The topical composition of the present disclosure may contain, in addition to the above-mentioned components (A) to (C), a liquid fatty acid (sometimes referred to as component (E)) as necessary. A liquid fatty acid is a fatty acid that is liquid at 20° C. The number of carbon atoms in a liquid fatty acid is, for example, 12 to 22, and preferably 16 to 20. The hydrocarbon chain constituting the liquid fatty acid may be either a saturated hydrocarbon or an unsaturated hydrocarbon, and may be either a straight chain or a branched chain.

[0042] Specific examples of liquid fatty acids include linear unsaturated fatty acids such as oleic acid, linoleic acid, and linolenic acid; and branched saturated fatty acids such as isostearic acid and isopalmitic acid.

[0043] These liquid fatty acids may be used alone or in combination of two or more.

[0044] Among these liquid fatty acids, from the viewpoint of further improving the effect of promoting penetration into the skin and the effect of suppressing phase separation, branched saturated fatty acids are preferred, and isostearic acid is more preferred.

[0045] When a liquid fatty acid is contained in the topical composition of the present disclosure, the content thereof is, for example, 0.00001 to 1 wt %, preferably 0.00005 to 0.1 wt %, and more preferably 0.0001 to 0.001 wt %.

[0046] [water] The topical composition of the present disclosure preferably contains water as a base material. The content of water in the topical composition of the present disclosure may be the balance other than the components (A) to (C), the components (D) and (E) which are blended as necessary, and other components described later.

[0047] [Other ingredients] In addition to the above-mentioned components, the topical composition of the present disclosure may contain other additives that are commonly used in topical compositions, if necessary. Examples of such additives include monohydric lower alcohols, oils other than component (E), surfactants other than components (B) and (D), buffers, pH adjusters, solubilizers, preservatives, antioxidants, stabilizers, fragrances, colorants, etc. When these additives are contained in the topical composition of the present disclosure, the content of the additives may be appropriately set according to the type of additives used, etc.

[0048] The topical composition of the present disclosure may contain lipophilic active ingredients in addition to the above-mentioned ingredients. Examples of such lipophilic active ingredients include antihistamines, local anesthetics, anti-inflammatory agents, moisturizers, bactericides, antibacterial agents, antipruritic agents, skin protectants, blood circulation promoting ingredients, vitamins, etc. These lipophilic active ingredients may be used alone or in combination of two or more. In addition, when these lipophilic active ingredients are contained in the topical composition of the present disclosure, their concentration may be appropriately set according to the type of lipophilic active ingredient used, the effect expected, etc.

[0049] [Dosage form / formulation] The dosage form of the topical composition of the present disclosure is not particularly limited as long as it is applicable transdermally, and may be any of liquid, semi-solid (cream, gel, ointment, paste), solid, etc., but preferably liquid or semi-solid. The topical composition of the present disclosure may be an emulsion preparation such as an oil-in-water emulsion preparation or a water-in-oil emulsion preparation, or may be a non-emulsion preparation such as a solubilized preparation or an aqueous ointment.

[0050] Furthermore, the topical composition of the present disclosure may be in any formulation, such as a topical drug for skin application (including quasi-drugs), a cosmetic, or a skin cleanser, so long as it is applied to the skin.

[0051] Specific examples of the formulation of the topical composition of the present disclosure include topical skin medicines such as creams, lotions, gels, emulsions, liquids, poultices, patches, liniments, aerosols, aqueous ointments, and packs; cosmetics such as aqueous ointments, creams, emulsions, skin lotions, lotions, packs, and gels; skin cleansers such as body shampoos, hair shampoos, and rinses. Among these, topical skin medicines and cosmetics are preferred, and cosmetics are more preferred.

[0052] [Manufacturing method] The topical composition of the present disclosure can be produced by mixing the above-mentioned (A) to (C) components, the (D) component, the (E) component, water, and other components that are blended as necessary, and preparing them into a desired formulation form. The topical composition of the present disclosure contains the above-mentioned (A) to (C) components, which makes it easier for the components to be uniformly dispersed during production, and also has the advantage in terms of production that the components can be easily and uniformly dispersed. EXAMPLES

[0053] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0054] Test Example 1 1. Test Method A composition for external use was prepared by adding and stirring each of the components shown in Table 1. The obtained composition for external use was evaluated for the permeability, dispersibility and stability of tranexamic acid (a water-soluble active ingredient) into the epidermis, as well as the color tone, by the following methods.

[0055] (1) Epidermal penetration of tranexamic acid (a water-soluble active ingredient) A three-dimensional cultured skin model (EPI-200X, MatTek) was attached to a dedicated fixing device and placed in a 24-well plate of a receiver. 50 μL of the topical composition was added to the skin model side, and 2 mL of EPI-100 Assay X medium (MatTek) was added to the receiver side. After standing at 37 ° C for 10 hours, the skin model was collected, and the surface of the skin model was thoroughly washed with PBS. The washed skin model was frozen, and a skin slice was prepared. The peak intensity derived from tranexamic acid of the obtained skin slice was measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) to determine the amount of tranexamic acid contained in the skin slice. The amount of tranexamic acid in the skin slice measured with the topical composition of Comparative Example 1 was used as the reference value, and the effect was evaluated according to the following criteria. <Standards> A: The amount of tranexamic acid in the skin section is more than twice the standard value. B: The amount of tranexamic acid in the skin section is more than 1-fold and less than 2-fold the standard value. C: The amount of tranexamic acid in the skin section is less than 1-fold the standard value.

[0056] (2) Dispersibility and stability When preparing the topical composition, the stirring conditions required to uniformly disperse each component were evaluated, and the presence or absence of separation and precipitation when the obtained topical composition was left to stand for one day was evaluated, and the effectiveness was judged according to the following criteria. <Standards> A: The ingredients were uniformly dispersed with normal stirring without the need for heating or ultrasonic treatment during preparation, and no separation or precipitation was observed in the obtained topical composition even after it was left to stand. B: During preparation, heating or ultrasonic treatment was required to uniformly disperse the ingredients, but no phase separation or precipitation was observed in the obtained topical composition even after standing. C: Heating or ultrasonic treatment was required during preparation to uniformly disperse the ingredients, and separation or precipitation was observed in the obtained topical composition after standing. D: Even when heating or ultrasonic treatment was performed during preparation, the components could not be uniformly dispersed.

[0057] (3) Color tone The color tone of each topical composition was visually confirmed, and the effectiveness was evaluated according to the following criteria. <Standards> A: The composition for external use is colorless or slightly cloudy. B: The composition for external use is cloudy.

[0058] 2. Test Results The results are shown in Table 1. As a result, when tranexamic acid and hydrogenated lecithin were included, the permeability of tranexamic acid into the epidermis was improved, but heating or ultrasonic treatment was required to uniformly disperse the ingredients during preparation, and separation or precipitation of the ingredients was observed during storage. In contrast, when tranexamic acid, a polyglyceric acid fatty acid ester, and a polyol were included, the permeability of tranexamic acid into the epidermis was improved, and it was easy to uniformly disperse the ingredients during preparation, and separation or precipitation of the ingredients during storage was not observed.

[0059] [Table 1]

[0060] Test Example 2 1. Test Method Cream-type compositions for external use shown in Table 2 were prepared, and the permeability of tranexamic acid into human skin was evaluated by the following method.

[0061] The inside of a human forearm was washed with soap and allowed to acclimate at room temperature for 20 minutes. 20 μL of the topical composition was applied to the acclimatized inside of the human forearm at a distance of 4.5 cm. 2The topical composition was applied to the same skin site once every hour for a total of six times. One hour after the sixth application, the topical composition remaining on the skin was removed, and the stratum corneum at the application site of the topical composition was peeled off ten times by tape stripping. The peak intensity derived from tranexamic acid was measured by TOF-SIMS for the fourth tape (stratum corneum of the body surface), the eighth tape (stratum corneum intermediate between the body surface and the deep part), and the tenth tape (stratum corneum of the deep part) in the tape stripping method, and the amount of tranexamic acid was determined. The amount of tranexamic acid in the stratum corneum attached to each tape when the topical composition of Comparative Example 3 was applied was used as the reference value, and the effect was evaluated according to the following criteria. <Standards> AA: The amount of tranexamic acid in the stratum corneum adhering to the tape is 1.5 times or more the standard value. A: The amount of tranexamic acid in the stratum corneum adhering to the tape is more than 1.25 times and less than 1.5 times the standard value. B: The amount of tranexamic acid in the stratum corneum adhering to the tape is more than 1 and less than 1.25 times the standard value. C: The amount of tranexamic acid in the stratum corneum adhering to the tape is less than 1x the standard value.

[0062] 2. Test Results The results obtained are shown in Table 2. As a result, it was confirmed that the topical composition containing tranexamic acid, polyglyceric acid fatty acid ester, and polyol can promote the penetration of tranexamic acid into human skin.

[0063] [Table 2]

[0064] Prescription Examples Creams (Formulation Examples 1 to 30) having the compositions shown in Tables 3 and 4, milky lotions (Formulation Examples 31 to 54) having the compositions shown in Tables 5 and 6, and lotions (Formulation Examples 55 to 78) having the compositions shown in Tables 7 and 8 were prepared. The obtained creams, milky lotions, and lotions were evaluated by the method shown in Test Example 1, and it was found that the penetration of the water-soluble active ingredient into the skin was promoted and phase separation due to storage was suppressed in all cases.

[0065] [Table 3]

[0066] [Table 4]

[0067] [Table 5]

[0068] [Table 6]

[0069] [Table 7]

[0070] [Table 8]

Claims

1. A composition for external use comprising (A) a water-soluble active ingredient, (B) a polyglycerol fatty acid ester, and (C) a polyol.

2. The topical composition according to claim 1, further comprising (D) a dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester.

3. The composition for external use according to claim 1 or 2, further comprising (E) a liquid fatty acid.

4. 3. The composition for external use according to claim 1 or 2, wherein the (A) water-soluble active ingredient is at least one selected from the group consisting of tranexamic acid, arbutin, ascorbic acid, salts of ascorbic acid, ascorbic acid derivatives, nicotinic acid, and nicotinic acid derivatives.

5. The composition for external use according to claim 1 or 2, wherein the water-soluble active ingredient (A) is tranexamic acid.

6. The composition for external use according to claim 1 or 2, wherein the (B) polyglycerin fatty acid ester is at least one selected from the group consisting of polyglyceryl monolaurate, polyglyceryl diisostearate, polyglyceryl monocaprate, polyglyceryl monocaprylate, polyglyceryl dilaurate, polyglyceryl trilaurate, polyglyceryl myristate, polyglyceryl dimyristate, polyglyceryl trimyristate, polyglyceryl monooleate, polyglyceryl dioleate, polyglyceryl trioleate, polyglyceryl monostearate, polyglyceryl distearate, polyglyceryl tristearate, polyglyceryl monoisostearate, polyglyceryl (eicosane diacid / tetradecane diacid), polyglyceryl (isostearate / succinate), and polyglyceryl penta(behenate / eicosane diacid).

7. The composition for external use according to claim 1 or 2, wherein the HLB value of the (B) polyglycerol fatty acid ester is 10 or more.

8. The composition for external use according to claim 1 or 2, wherein the (B) polyglycerol fatty acid ester is polyglyceryl monolaurate and / or polyglyceryl diisostearate.

9. The composition for external use according to claim 1 or 2, wherein the (C) polyol is glycerin.

10. The topical composition for external use according to claim 2, wherein the (D) dicarboxylic acid bis(polyoxyalkylene alkyl ether) ester is cyclohexane-1,4-dicarboxylate bisethoxydiglycol.

11. The composition for external use according to claim 3 , wherein the liquid fatty acid (E) is isostearic acid.

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