WO2016002787A1

WO2016002787A1 - External preparation

Info

Publication number: WO2016002787A1
Application number: PCT/JP2015/068846
Authority: WO
Inventors: 幸恵藤田; 賢太升田
Original assignee: ロート製薬株式会社
Priority date: 2014-06-30
Filing date: 2015-06-30
Publication date: 2016-01-07
Also published as: CN106456484A; JP2016027037A; JP6883378B2

Abstract

Provided is an external preparation containing (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by formula (I) or a salt thereof. (In formula (I), R^a indicates a C7-19 linear alkyl group or a group represented by –NR^dR^e, R^d and R^e each independently indicate a hydrogen atom or optionally substituted alkyl group, R^b and R^c each independently indicate a hydrogen atom, optionally substituted alkyl group, or group represented by formula (II). Here, R^b and R^c may bond to each other to form a ring. Substituents are a hydroxyl group, carboxy group, alkyl group, or group represented by formula (III). In formula (II), R^f indicates a hydrogen atom or an alkyl group optionally substituted by a hydroxyl group.

Description

Topical preparation

The present invention relates to an external preparation.

Tranexamic acid is known for its pigmentation-inhibiting action and is used in various cosmetics for whitening. On the other hand, tranexamic acid has a problem that it is colored over time under conditions such as exposure to sunlight and high temperatures. In addition, there is a problem that coloring occurs when tranexamic acid is used in combination with sugars.

As means for suppressing coloration when tranexamic acid is used in combination with saccharides, for example, Patent Document 1 discloses a composition containing tranexamic acids and saccharides, inorganic acids or salts thereof, organic acids or salts thereof, alcohols. A cosmetic composition is disclosed, characterized in that one or more selected from the group of vitamins, vitamins or derivatives thereof, chelating agents, and plant, seaweed or animal-derived components are blended.

JP 2014-062077 A

In the cosmetic composition described in Patent Document 1, sodium pyrosulfite is mainly used as an inorganic salt. However, sodium pyrosulfite may have an unpleasant odor over time and was not suitable for unscented formulations. In addition, this odor could not be hidden even when a fragrance was used.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an external preparation in which coloring over time is suppressed in an external preparation containing tranexamic acid and a saccharide.

The inventors of the present invention include a composition containing (A) tranexamic acid (hereinafter also referred to as “(A) component”) and (B) saccharide (hereinafter also referred to as “(B) component”). Furthermore, it discovered that coloring of a composition can be suppressed by adding the compound or its salt (henceforth "(C) component") represented by (C) Formula (I). The present invention is based on these findings.

The present invention provides, for example, the following [1] to [11].
[1] An external preparation containing (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by the formula (I) or a salt thereof.

[In the formula (I), R ^a represents a linear alkyl group having 7 to 19 carbon atoms or a group represented by —NR ^d R ^e , wherein R ^d and R ^e each independently represents a hydrogen atom, Or an alkyl group which may have a substituent, and R ^b and R ^c are each independently a hydrogen atom, an alkyl group which may have a substituent, or a group represented by the formula (II) Indicates a group. Here, R ^b and R ^c may be bonded to each other to form a ring. The substituent is a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III).

In formula (II), R ^f represents a hydrogen atom or an alkyl group which may be substituted with a hydroxyl group.

[2] The external preparation according to [1], wherein the compound represented by the formula (I) is a compound represented by the formula (1).

(Wherein R ¹ represents any of the groups represented by formulas (2) to (23), and n represents an integer of 6 to 18)

[3] The external preparation according to [1], wherein the compound represented by the formula (I) is a compound represented by the formula (24).

^(Wherein, ^R ^b, R ^c, R ^d and ^{R e} have the same meanings as ^{^R} ^b, ^R ^c, ^R ^d and ^{R e} in the formula (I).)
[4] The component (C) is at least one selected from the group consisting of N-capryloyl acylglycine, N-decanoyl-L-proline, N-stearoyl-L-glutamic acid, allantoin and alcloxa, and salts thereof The external preparation described in [1].
[5] The external preparation according to any one of [1] to [4], wherein the component (B) is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides and glycosides.
[6] An external preparation for use in whitening, suppression or improvement of inflammation, or improvement of rough skin, wherein (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) formula (I) An external preparation containing the represented compound or a salt thereof.
[7] Use of an external preparation for whitening, suppression or improvement of inflammation, or improvement of rough skin, wherein the external preparation is (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) formula ( A compound comprising a compound represented by I) or a salt thereof.
[8] Use of an external preparation for producing a whitening agent, an agent for suppressing or improving inflammation, or an agent for improving rough skin, wherein the external preparation comprises (A) tranexamic acid or a salt thereof, and (B) a saccharide. And (C) a compound represented by formula (I) or a salt thereof.
[9] including a step of applying to the skin an external preparation containing (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by formula (I) or a salt thereof. , A whitening method, a method for suppressing or improving inflammation, or a method for improving rough skin.
[10] The external preparation is colored by adding (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by the formula (I) or a salt thereof to the external preparation. How to suppress.
[11] By adding (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by formula (1) or a salt thereof to the external preparation, coloring of the external preparation and A method for suppressing changes in pH.

According to the present invention, in an external preparation containing tranexamic acid and saccharides, it is possible to provide an external preparation in which coloring due to heat or passage of time is suppressed.

Hereinafter, a mode for carrying out the present invention (hereinafter referred to as “the present embodiment”) will be described in detail. In addition, this invention is not limited to the following embodiment.

The external preparation of this embodiment contains (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by formula (I) or a salt thereof.

In the formula (I), R ^a represents a linear alkyl group having 7 to 19 carbon atoms or a group represented by —NR ^d R ^e , and R ^d and R ^e are each independently a hydrogen atom, or An alkyl group which may have a substituent, R ^b and R ^c each independently represent a hydrogen atom, an alkyl group which may have a substituent, or a group represented by the formula (II); Indicates. Here, R ^b and R ^c may be bonded to each other to form a ring. The substituent is a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III).

(A) Tranexamic acid or a salt thereof Tranexamic acid is a compound also referred to as trans-4- (aminomethyl) cyclohexane-1-carboxylic acid, and may be synthesized by a known method or obtained as a commercial product. You can also.

The salt of tranexamic acid is not particularly limited as long as it is pharmacologically (pharmaceutically) or physiologically acceptable as an external preparation. Examples of salts of tranexamic acid include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; zinc salt; iron salt; ammonium salt; arginine, lysine, histidine, ornithine and the like. And salts with amines such as monoethanolamine, diethanolamine, and triethanolamine. As the salt of tranexamic acid, among them, sodium salt, potassium salt, triethanolamine salt and arginine salt are preferable, and sodium salt is more preferable.

Tranexamic acid or a salt thereof may be used alone or in combination of two or more.

The content of the component (A) in the external preparation of the present embodiment is, for example, preferably based on the total amount of the external preparation, and the total content of the component (A) is usually 0.01 to 5% by weight, It is more preferably 0.1 to 3% by weight, and further preferably 0.5 to 2% by weight. When the content of the component (A) is in the above range, the effect of the present invention can be further enhanced. When the content of the component (A) is in the above range, in addition to the effects of the present invention, effects such as whitening, anti-inflammation, and rough skin improvement of tranexamic acid or a salt thereof can be obtained.

(B) Saccharides Saccharides are not particularly limited as long as they are used in normal skin external compositions, and examples thereof include monosaccharides, disaccharides, oligosaccharides, polysaccharides, glycosides, and sugar alcohols.

Examples of monosaccharides include tetroses such as D-erythrulose, D-erythrose, and D-threose; aldopentoses such as D-arabinose, L-arabinose, D-xylose, D-lyxose, L-lyxose, and D-ribose. Ketopentoses such as D-xylulose, L-xylulose, D-ribulose and L-ribulose; Aldohexoses such as D-galactose, L-galactose, D-glucose, D-talose and D-mannose; L-sorbose Ketohexoses such as D-tagatose, D-psicose and D-fructose; branched saccharides such as D-apiose and D-hamamelose; pentoses such as ribose, arabinose and xylose; hexoses such as glucose, galactose and fructose; Emissions, amino sugars such as galactosamine; etc., or derivatives of these monosaccharides are mentioned.

Examples of disaccharides, oligosaccharides and glycosides thereof include homooligosaccharides containing one kind of the above-mentioned monosaccharides or derivatives thereof, or heterooligosaccharides containing two or more kinds. Examples of homooligosaccharides include xylo-oligosaccharides such as xylobiose, xylotriose, xylotetraose, and xylopentaose; galactooligosaccharides such as agarobiose and carabiose; maltose, maltotriose, maltotetraose, maltopentaose, isomaltose, Glyco-oligosaccharides such as sophorose, cellobiose, cellotriose, cellotetraose, cellopentaose, trehalose, neotrehalose, and isotrehalose; manno-oligosaccharides; fructooligosaccharides such as inulobiose, inrotriose, inulotetraose, and inulopentaose . Hetero-oligosaccharides include vicyanose, isoprimebellose, sambubiose, primebellose, lycotetraose, sorabiose, melibiose, manninotriose, lactose, lycobiose, lycotriose, epicellobiose, sucrose, turanose, maltulose, isochestose, erulose, kestose , Gentianose, lactulose, epigentibose, isoliquenose, umbelliferose, sesame, raffinose, lycnose, robinobiose, silanobiose, rutinose, cacotriose, soratriose, α-glucan oligosaccharide (glucose oligomer having a degree of polymerization of 2 to 10), etc. Can be mentioned.

Examples of the polysaccharide include polysaccharides such as xanthan gum, cellulose, guar gum, starch, pullulan, dextran, fructan, mannan, agar, carrageenan, chitin, chitosan, pectin, alginic acid, starch, glycogen, and hyaluronic acid. Polysaccharides also include derivatives in which these sugars are substituted with methyl, ethyl, hydroxyethyl, hydroxypropyl, acetyl, stearoxy, glycerol, propylene glycol, and the like. These substituents can be substituted singly or in a plurality of combinations. Specific examples of the polysaccharide having a substituent include hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxyethyl guar gum, hydroxyethyl starch, methyl cellulose, methyl guar gum, methyl starch, ethyl cellulose, ethyl guar gum, ethyl starch, hydroxypropyl cellulose, hydroxypropyl Guar gum, hydroxypropyl starch, hydroxyethyl methyl cellulose, hydroxyethyl methyl guar gum, hydroxyethyl methyl starch, hydroxypropyl methyl cellulose, hydroxypropyl methyl guar gum, hydroxypropyl methyl starch, stearoxy hydroxypropyl methyl cellulose, acetylated hyaluronic acid, propylene glycol alginate, hyaluro Such as propylene glycol and the like.

Examples of glycosides include arbutin, ascorbic acid glucoside, glucosylceramide, anthocyanin, rutin, hesperidin, and daidzin.

Examples of sugar alcohols include xylitol, trehalose, maltitol, mannitol, sorbitol, erythritol, arabitol, ribitol, galactitol, glucitol, and erythritol.

Among these sugars, glucose, arabinose, galactose, mannose, maltose, fructose, lactose, α-glucan oligosaccharide, carrageenan, dextrin, pectin, hyaluronic acid, sodium hyaluronate, sodium acetylhyaluronate, hydrolyzed hyaluronic acid, hyaluronic acid Hydroxypropyltriammonium, hydrolyzed zinc hyaluronate, sodium hyaluronate crosspolymer, hyaluronic acid PG, chondroitin sulfate, soluble collagen, curdlan, xanthan gum, carrageenan, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose Hydroxypropylmethylcellulose, Thione cellulose, alginates, cyclodextrin, dextran, pullulan, arbutin, ascorbic acid glucoside is preferred. Sugars include glucose, maltose, fructose, lactose, α-glucan oligosaccharide, hyaluronic acid, hyaluronic acid, sodium hyaluronate, sodium acetyl hyaluronate, hydrolyzed hyaluronic acid, hydroxypropyltriammonium hyaluronate, hydrolyzed zinc hyaluronate , Hyaluronic acid crosspolymer sodium, hyaluronic acid PG, xanthan gum, carrageenan, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, cationizedcellulose, alginate, arbutin, ascorbic acid glucoside, etc. More preferred. As the saccharide, glucose, maltose, fructose, lactose, α-glucan oligosaccharide, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, alginate, methylcellulose, arbutin, ascorbic acid glucoside and the like are more preferable.

Sugars may be used alone or in combination of two or more.

The content of the component (B) in the external preparation of the present embodiment is preferably 0.01 to 7% by weight, more preferably 0.05 to 5% by weight, based on the total amount of the component (B). More preferably, the content is 0.1 to 3% by weight. If content of (B) component is the said range, the effect by this invention can be improved further.

(C) Compound represented by formula (I) or salt thereof R ^a in formula (I) of component (C) according to this embodiment is a linear alkyl group having 7 to 19 carbon atoms, or —NR ^d R ^The group represented by ^e is shown. R ^d and R ^e each independently represent a hydrogen atom or an alkyl group, and the alkyl group may have a substituent. The substituent may be a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III), and may be a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III). Is more preferable, and a group represented by the formula (III) is more preferable.

R ^b and R ^{c in} formula (I) each independently represent a hydrogen atom, an alkyl group, or a group represented by formula (II), and the alkyl group may have a substituent. The substituent may be a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III), and is preferably a hydroxyl group, a carboxy group, or an alkyl group. R ^b and R ^c may be bonded to each other to form a ring.

The compound represented by the formula (I) is preferably a compound represented by the formula (1) or the formula (24).

In formula (1), R ¹ represents any of the groups represented by formulas (2) to (23), and n represents an integer of 6 to 18.

In the formula (24), R ^b , R ^c , R ^d and R ^e are as described above.

R ¹ in formula (1) is not particularly limited as long as it is any of the groups represented by formulas (2) to (23). When the external preparation of this embodiment contains the compound represented by the formula (1) as the component (C), in addition to the effect of suppressing the coloration of the external preparation, the change in the pH of the external preparation is suppressed. You can also. It is preferable that the pH of the external preparation does not change because it may cause discoloration of the external preparation depending on the active ingredient contained therein, or may cause a change in feeling of use or properties because it is involved in the viscosity of the external preparation. From the viewpoint of further suppressing coloring and pH change of the external preparation of the present embodiment, R ¹ in formula (1) is represented by formula (2), formula (3), formula (9), formula (10), formula It is preferable that it is group shown by (11), Formula (22), or Formula (23), and Formula (2), Formula (9), or Formula (11) is more preferable. N in the compound represented by the formula (1) is preferably 6 to 18, and more preferably 7 to 18. From the viewpoint of further suppressing coloring and pH change of the external preparation of the present embodiment, examples of the compound represented by the formula (1) include N-capryloyl acylglycine, N-decanoyl-L-proline, and N -Stearoyl-L-glutamic acid is preferred.

From the viewpoint of further suppressing the coloring of the external preparation of the present embodiment, examples of the compound represented by the formula (24) include allantoin ((2,5-dioxo-4-imidazolidinyl) urea) or a salt thereof, Alternatively, it is preferably imidazolidinyl urea (N, N′-methylenebis [N ′-(3-hydroxymethyl-2,5-dioxo-4-imidazolidinyl) urea), more preferably allantoin or a salt thereof.

The salt of component C) is not particularly limited as long as it is a pharmacologically (pharmaceutically) or physiologically acceptable salt as an external preparation. Examples of the salt of component (C) include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; aluminum salts such as hydroxyaluminum salts; zinc salts; iron salts; Salts; salts with basic amino acids such as arginine, lysine, histidine, ornithine; salts with amines such as monoethanolamine, diethanolamine, triethanolamine, and the like. Among them, the salt of the component (C) is preferably a sodium salt, potassium salt, triethanolamine salt or arginine salt, more preferably a sodium salt. As the salt of allantoin, alcloxa (aluminum chlorohydroxy allantoinate) is preferable.

(C) A component may be used individually by 1 type and may be used in combination of 2 or more type.

The content of the component (C) in the external preparation of the present embodiment is, for example, preferably based on the total amount of the external preparation, and the total content of the component (C) is usually 0.01 to 10% by weight. 0.05 to 8% by weight is more preferable, and 0.1 to 5% by weight is still more preferable. When component (C) is allantoin, alcloxa, imidazolidinyl urea, or a salt thereof, the content thereof is, for example, based on the total amount of the external preparation, the total content of component (C) is 0.01 to 5 % By weight is preferable, 0.05 to 2% by weight is more preferable, and 0.1 to 1% by weight is still more preferable. If content of (C) component exists in the said range, the effect by this invention can be improved further.

The content of the component (C) in the external preparation of the present embodiment can be appropriately adjusted depending on the saccharide used. The content of component (C) is preferably 0.05 to 5 parts by weight, more preferably 0.1 to 4 parts by weight, further 0.15 to 3.0 parts by weight per part by weight of component (B). preferable. If the component (C) is contained in a proportion within the above range with respect to the component (B), the coloration or pH change of the external preparation of the present embodiment can be sufficiently suppressed, and it occurs with the coloring reaction. There is a tendency to suppress odor.

The method for producing the compound represented by the formula (I) is not particularly limited. In the method for producing the compound represented by formula (I), for example, a derivative may be prepared by condensing a compound having an amino group and a compound having a carboxyl group. The manufacturing method of the compound represented by Formula (1) is not specifically limited. In the method for producing the compound represented by the formula (1), for example, a derivative may be prepared by condensing an amino group of an amino acid and a carboxyl group of a fatty acid. The manufacturing method of the compound represented by Formula (24) is not specifically limited. In the method for producing the compound represented by the formula (24), for example, a derivative may be prepared by oxidizing urea.

The external preparation of this embodiment may be any of pharmaceuticals, quasi drugs, and cosmetics. The external preparation of this embodiment is preferably a skin external preparation applied to the skin.

The form of the external preparation of this embodiment used for pharmaceuticals is not particularly limited, and examples thereof include solutions, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and aerosols. . These preparations can be manufactured according to the method described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations. As the form of the external preparation, liquids, suspensions, emulsions, creams, ointments, gels, lotions, and aerosols are preferable, and liquids, suspensions, creams, emulsions, and gels are preferable. More preferred.

Also when it is set as the external preparation used for quasi-drugs or cosmetics, it can be made into the same form as said external preparation for pharmaceuticals. In addition, the form of the external preparation includes a stick agent or a sheet agent obtained by impregnating a non-woven fabric with a chemical solution. As the form of the external preparation used for quasi-drugs or cosmetics, among them, liquids, suspensions, emulsions, creams, ointments, gels, lotions and sheets are preferred, liquids, suspensions, Creams, emulsions and gels are more preferred.

When the external preparation of this embodiment includes an oily base and an aqueous base such as creams and emulsions, it may be W / O type or O / W type. The external preparation of this embodiment is preferably an O / W type.

Examples of the application in the case of quasi-drugs or external preparations for cosmetics include, for example, lotion, milky lotion, gel, cream, serum, cosmetic for sunscreen, pack, mask, hand cream, body lotion, body cream Basic cosmetics such as facial cleansers, makeup removers, shaving agents, body shampoos, shampoos, rinses, treatments, etc .; lip cosmetics such as lip balms and lipsticks; makeup cosmetics such as foundations and mascaras Hair removal agents; and bathing agents.

In addition to the above components, the external preparation of the present embodiment can contain a base or carrier that is usually used for pharmaceuticals, quasi drugs, or cosmetics. Moreover, the external preparation of this embodiment can contain an additive as needed.

The base or carrier contained in the external preparation of the present embodiment includes, for example, liquid paraffin, squalane, petrolatum, gelled hydrocarbon (such as plastibase), ozokerite, α-olefin oligomer, light liquid paraffin, and other hydrocarbons; methyl Polysiloxane, cross-linked methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linkable polyether-modified silicone, cross-linking Type alkyl polyether-modified silicone, silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyg Serine modified branched silicone, acrylic silicone, phenyl modified silicone, silicone resin such as silicone resin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol; sterols such as cholesterol, phytosterol, phytosteryl hydroxystearate; jojoba oil, Vegetable oils such as meadow foam oil, sunflower oil, grape seed oil, grape oil, squalane, shea butter, rice germ oil; animal oils such as lanolin, orange luffy oil, squalane, horse oil; ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, cation Natural polymer derivatives such as modified guar gum and acetylated hyaluronic acid; polyvinylpyrrolidone, carboxyvinyl polymer, Synthetic polymers such as alkyl methacrylate copolymers; natural polymers such as carrageenan, alginic acid, cellulose, guar gum, quince seed, dextran, gellan gum, hyaluronic acid; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipic acid Polyesters; Esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate, jojoba oil, tri (caprylic acid / capric acid) glyceryl; Polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; polyhydric alcohols having 2 to 6 carbon atoms and 2 to 4 hydroxyl groups as described above ; Glycol ether described above; and the like aqueous base, such as well water; succinic, glycolic, gluconic acid, organic acids such as citric acid. As the base or carrier contained in the external preparation of the present embodiment, among them, polyhydric alcohols, higher alcohols, hydrocarbons, esters and silicone oils are preferable, and polyhydric alcohols are more preferable.

Favorable examples of the external preparation of the present embodiment include solutions, suspensions, creams, emulsions and gels containing a polyhydric alcohol as a base.

As the base or carrier, one type may be used alone, or two or more types may be used in combination.

In the external preparation of the present embodiment, known additives that are added to pharmaceuticals, quasi drugs, or cosmetics can be added as long as the effects of the present invention are not impaired. Additives include, for example, antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, cooling agents, fragrances, and pearl luster imparting agents. Etc.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivative, tocopherol, tocopherol derivative, erythorbic acid, L-cysteine hydrochloride and the like.

Examples of the surfactant include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate. Sorbitan fatty acid esters; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor Hardened castor oil derivatives such as oil 60 (HCO-60), polyoxyethylene hardened castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), monostearate Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene acid (20) sorbitan (polysorbate 60), polyoxyethylene monooleate (20) sorbitan (polysorbate 80), polyoxyethylene (20) sorbitan isostearate; polyoxy Glyceryl alkyl ether; alkyl glucoside such as cetostearyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether and polyoxyethylene behenyl ether; amines such as stearylamine and oleylamine; polyoxyethylene・ Methyl polysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxye Silicone surfactants such as rudimethicone; natural surfactants such as phospholipids, surfactins, saponins; fatty acid amidoamines such as diethylaminoethylamide stearate and diethylaminopropyl stearate; trilaurylamine, dimethylstearylamine, di- Examples include alkylamines such as 2-ethylhexylamine; betaine amphoteric surfactants such as stearic acid dimethylaminopropylamide and laurylhydroxysulfobetaine.

Examples of thickeners include guar gum, locust bean gum, carrageenan, hyaluronic acid, xanthan gum, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, alkyl methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, Examples thereof include cellulose thickeners such as sodium chondroitin sulfate, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and carboxyethyl cellulose.

Examples of preservatives or preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, paraoxybenzoate Examples include benzyl benzoate, methyl paraoxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediol, and glycerin fatty acid ester.

Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, sodium lactate, acetic acid, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid). , Sodium succinate, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, epsilon aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, Potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, etc.) and organic bases (monoethanolamine, triethanolamine, diisopropanolamine, lysine, triisopropanolamine, etc.).

Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole and the like.

Examples of the irritation reducing agent include licorice extract, sodium alginate, 2-methacryloyloxyethyl phosphorylcholine and the like.

Examples of chelating agents include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphoric acid And metaphosphoric acid. Among them, sodium edetate is preferable as the chelating agent.

Examples of the colorant include inorganic pigments and natural pigments.

Examples of the refreshing agent include menthol, menthoxypropanediol, monomenthyl glyceryl ether, menthyl lactate, camphor, eugenol, mint oil, peppermint oil and the like.

Examples of the pearl luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate. Among them, ethylene glycol distearate is preferable as the pearl luster imparting agent.

An additive may be used individually by 1 type, and may be used in combination of 2 or more type.

The external preparation of the present embodiment can contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of active ingredients include, for example, moisturizing ingredients, anti-inflammatory ingredients, antibacterial ingredients, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation ingredients, anti-aging ingredients, blood circulation promoting ingredients, keratin softening ingredients, Whitening components, astringent components, UV protection components (UV absorption components, UV scattering components) and the like can be mentioned.

Examples of moisturizing ingredients include lipids such as ceramide, cholesterol, and phospholipid; plant extract extracts such as chamomile extract, mulberry extract, docami extract, carrot extract, hamamelis extract, bilberry leaf extract, tea extract, perilla extract; hyaluronic acid, sodium hyaluronate , Acetyl hyaluronic acid, sodium acetyl hyaluronate, heparin analogues, chondroitin, chondroitin sulfate sodium and other mucopolysaccharides; collagen, elastin, keratin, chitin, chitosan and other high molecular compounds; glycerin, 1,3-butylene glycol, propylene glycol , Polyethylene glycols, and polyhydric alcohols such as diglycerin trehalose; alanine, serine, leucine, isoleucine, threonine, glycine, proline, Amino acids such as droxyproline, glucosamine, aspartic acid, theanine, arginine; natural moisturizing factors such as sodium lactate, urea, sodium pyrrolidonecarboxylate; sugar alcohols such as sorbitol; phospholipids such as lecithin, hydrogenated lecithin; polyglutamic acid; Polymer having a phospholipid polar group such as MPC polymer (for example, LIPIDURE®); polyoxypropylene methylglucoside; trimethylglycine (betaine); hydroxyethylurea; acrylic acid / acrylamide / dimethyldiallylammonium chloride co-polymer Examples include coalescence. Among these moisturizers, in consideration of usability, lipids such as ceramide, cholesterol and phospholipid; plant extract extracts such as mulberry extract, docami extract, carrot extract and bilberry leaf extract are preferable.

Examples of the anti-inflammatory component include components derived from plants (eg, grapes, ginseng, and comfrey), allantoin, glycyrrhizic acid or derivatives thereof, zinc oxide, pyridoxine hydrochloride, salicylic acid or derivatives thereof, and ε-aminocaproic acid. , Proanthocyanidins, tocopherols or derivatives thereof, ascorbic acid or derivatives thereof, hesperidin, glucosyl hesperidin, ergothioneine, sodium bisulfite, erythorbic acid or salts thereof, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase Thioredoxin, taurine, thiotaurine, hypotaurine and the like.

Antibacterial or bactericidal components include, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcin, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, popidone iodine, iodine Potassium halide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, alkanediol such as paraben, phenoxyethanol, 1,2-pentanediol, glycerin fatty acid ester, azelaic acid, alkyldiaminoglycine hydrochloride Chlorohexidine gluconate, zinc paraphenolsulfonate, and the like.

As vitamins, for example, retinol derivatives such as retinol, retinol acetate, retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocopheryl Vitamin A such as retinoate, β-tocopheryl retinoate; provitamin A such as β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthine, echinone; δ-tocopherol, Vitamin Es such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, tocopherol nicotinate; riboflavin, flavin mononucleo Vitamin B2 such as flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate; nicotinic acid dl-α-tocopherol, benzyl nicotinate, nicotinic acid Nicotinic acids such as methyl, β-butoxyethyl nicotinate, 1- (4-methylphenyl) ethyl nicotinate; ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), Ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, glucoscorbate Vitamin C such as methyl hesperidin, ergocalciferol and cholecalciferol; vitamin K such as phylloquinone and farnoquinone; dibenzoyl; ascorbigen-A, ascorbic acid stearate, ascorbyl palmitate Thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate Vitamin B such as salt, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate and pyridoxamine hydrochloride; Vitamin B12 such as cyanocobalamin, hydroxocobalamin and deoxyadenosylcobalamin; Folic acid such as folic acid and pteroylglutamic acid Nicotinic acids such as nicotinic acid and nicotinic acid amide; pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthecin, D-panthetin, coenzyme A, pantothenyl ethyl ether; Biotins such as bioticin; ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate Vitamin Cs which are ascorbic acid derivatives; vitamin-like agents such as γ-oryzanol, carnitine, ferulic acid, α-lipoic acid, orotic acid and the like.

Peptides or derivatives thereof include, for example, keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin Degraded peptide, conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soy proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein Degraded peptides, acylated peptides (palmitoyl oligopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc.) and the like can be mentioned.

Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine Methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.

Examples of the cell activation component include amino acids such as γ-aminobutyric acid and ε-aminoproic acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; Tannin; flavonoid; saponin; allantoin;

Examples of the anti-aging component include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivative, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like.

Examples of the blood circulation promoting component include plants (e.g., ginseng, ashitaba, arnica, ginkgo, fennel, enmelio, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, papaver, Senkyu, assembly, thyme, clove, chimpi, spruce, spruce, spruce, carrot, garlic, butcher bloom, grapes, buttons, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, spruce, spruce, peach, apricot , Walnut, or corn); glucosyl hesperidin and the like.

Examples of the keratin softening component include urea, salicylic acid, glycolic acid, gluconic acid, fruit acid, phytic acid, lanolin, lactic acid, lactate, citric acid, and sulfur.

Examples of the whitening component include arbutin; hydroquinone; kojic acid; ellagic acid; phytic acid; lucinol; chamomile ET; ascorbic acid or a derivative thereof; vitamin E or a derivative thereof; pantothenic acid or a derivative thereof; For example, plant extract or essential oil).

Examples of the astringent component include alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, zinc paraphenolsulfonate, zinc oxide, potassium aluminum sulfate and the like; tannic acid, citric acid, lactic acid, succinic acid And organic acids such as menthol and ethanol.

Examples of the ultraviolet ray absorbing component include 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyl). Oxycarbonyl) anilino] -1,3,5-triazine, dimethoxybenzylideneoxoimidazolidinepropionate 2-ethylhexyl, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl]- 6- (4-methoxyphenyl) -1,3,5-triazine, t-butylmethoxydibenzoylmethane, dibenzylidenedioxoimidazolidinepropyrate ethylhexyl, etorhexyltriazoline, paraaminobenzoic acid and its derivatives, paradimethyl Octyl aminobenzoate, sa Acrylic acid ethylene glycol, dihydroxy benzophenone.

Examples of the ultraviolet scattering component include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, hydrous silicic acid; Compounds coated with hydrous silicic acid, aluminum hydroxide, or inorganic powders such as mica and talc; those compounds compounded with resin powders such as polyamide, polyethylene, polyester, polystyrene or nylon; these And those treated with silicone oil, fatty acid aluminum salt, and the like.

Examples of the cleaning component include polyoxyalkylene alkyl (or alkenyl) ether sulfate, alkyl (or alkenyl) sulfate, higher fatty acid salts (such as palmitic acid, lauric acid, myristic acid, stearic acid), ether carboxylates, Amido ether carboxylate, alkyl phosphate ester salt, N-acyl amino acid salt (sodium N-lauroyl aspartate, potassium hydroxide / potassium coconut oil fatty acid acyl glutamate, coconut oil fatty acid acyl glycine sodium, myristoyl glutamic acid, etc.), Anionic surfactants such as polyoxyalkylene fatty acid amide ether sulfates, acylated isethionates, and acylated taurates; mono- or long-chain alkyl groups that may be added with alkylene oxide Is a cationic surfactant such as a di-long chain alkyl quaternary ammonium salt; carbobetaine, sulfobetaine, imidazolinium betaine (2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolium betaine, N-coconut oil fatty acid And amphoteric surfactants such as acyl-N-carboxymethoxyethyl-N-carboxymethylethylenediamine disodium) and amidobetaine.

Other active ingredients may be used alone or in combination of two or more.

The external preparation of this embodiment may be an external preparation packed in a container. Examples of container shapes include bottle types, tube types, jar types, spoid types, dispenser types, pouch bags, cheer packs, and the like. Examples of the container material include polyethylene terephthalate, polypropylene, polyethylene (such as HDPE, LDPE, and LLDPE), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, metal (such as aluminum), and the like. In consideration of the strength, flexibility, weather resistance, stability of components contained in the container, etc., the container containing these materials is subjected to various coating treatments, or these materials are mixed, for example. These can be combined into a container material, or layers made of these materials can be stacked to form a container material. In addition, those skilled in the art should appropriately select the diameter and material of the nozzle of the container and the discharge part of the preparation in order to adjust the discharge amount of the preparation from the container or reduce the adhesion of the preparation to the container. Can do.

The method for using the external preparation of the present embodiment varies depending on the state of the skin to be used, age, sex, etc., and examples thereof include the following methods. As for the method of use, the external preparation of the present embodiment may be applied to the skin several times a day (for example, 1 to 5 times, preferably 1 to 3 times) and an appropriate amount (for example, 0.05 to 5 g). Further, if the external preparation is applied so that the daily use amount of tranexamic acid is, for example, 0.00001 to 0.05 g, preferably 0.0001 to 0.02 g, more preferably 0.0002 to 0.01 g. Good. The application period of the external preparation may be, for example, 1 to 6 months, preferably 3 to 6 months.

The external preparation of the present embodiment can be suitably used for people who have skin spots, inflammation, etc. in anticipation of the physiological activity of tranexamic acid. The external preparation of this embodiment can also be suitably used for people having various other skin diseases or skin troubles. In addition, for the prevention of skin troubles, the external preparation of this embodiment is also suitable for use by people with normal skin.

The external preparation according to the present invention has effects such as whitening, suppression or improvement of inflammation, or improvement of rough skin due to the physiological activity of tranexamic acid. Therefore, the present invention can also be regarded as inventions according to the following embodiments.

As an embodiment of the present invention, an external preparation of the present invention for use in whitening, suppression or improvement of inflammation, or improvement of rough skin is provided.

As one embodiment of the present invention, use of the external preparation of the present invention for whitening, suppression or improvement of inflammation, or improvement of rough skin is provided.

As an embodiment of the present invention, there is provided use of the external preparation of the present invention for producing a whitening agent, an agent for suppressing or improving inflammation, or an agent for improving rough skin.

As one embodiment of the present invention, there is provided a whitening method, a method for suppressing or improving inflammation, or a method for improving rough skin, which comprises a step of applying (applying) the external preparation of the present invention to the skin.

In addition, the external preparation according to the present invention is one in which coloring of the external preparation due to heat or time passage is suppressed.

Therefore, as one embodiment of the present invention, (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by the formula (I) or a salt thereof are contained in an external preparation. Provides a method for suppressing coloring of the external preparation.

Furthermore, the external preparation according to the present invention is one in which coloring of the external preparation and change in pH with the passage of time or time are suppressed.

Therefore, as one embodiment of the present invention, (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by the formula (1) or a salt thereof are contained in an external preparation. Provides a method of suppressing coloring and pH change of the external preparation.

The essential components, other additives, and the contents thereof contained in the external preparation in each of the above embodiments are as described above.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

[Test Example 1: Measurement of color difference, odor and pH change of external preparation]
(1) Preparation of test solution The test solutions used in Examples and Comparative Examples were prepared by mixing various reagents at the mixing ratios shown in Tables 1 to 3.

(2) Test method The prepared test liquid was filled in a 20 mL capacity glass container, and the color difference, odor, and pH of the test liquid at 25 ° C were measured under the measurement conditions shown below. Thereafter, the test solution was transferred to a constant temperature bath at 60 ° C. and kept warm for one week. One week later, the test solution kept at 60 ° C. was taken out, made constant at 25 ° C., and various measurements were performed again.

(Color difference measurement)
1 mL of the test solution was placed in a glass cell (CM-A97, thickness 2 mm), and the color difference was measured with a spectrocolorimeter CM-5 (manufactured by Konica Minolta Co., Ltd.). The measured value was Δb * when purified water was used as a blank. The change in color difference was calculated by the following formula.
(Change in color difference) = (Measured value of test solution after incubation at 60 ° C)-(Measured value of test solution before incubation)

(Odor evaluation)
The odor of the test solution was evaluated as follows.
±: Even after the temperature was kept at 60 ° C., the odor was not changed from that before the temperature was kept.
+: After keeping the temperature at 60 ° C., the smell became stiff.

(Evaluation of pH)
The pH of the test solution was measured with a pH meter (HORIBA pH METER F-52, manufactured by Horiba, Ltd.). The change in pH was calculated by the following formula.
(Change in pH) = (pH of test solution after incubation at 60 ° C.) − (PH of test solution before incubation)

(Comprehensive evaluation)
The results of comparing the results of evaluating the color difference, odor, and pH of the test solution before and after maintaining at 60 ° C. were evaluated as follows.
(Double-circle): All the measured evaluation was favorable with respect to the comparative example used as a control | contrast.
○: Two of the measured evaluations were good with respect to the comparative example as a control.
(Triangle | delta): One of the measured evaluation was favorable with respect to the comparative example used as a control | contrast.
X: One of the measured evaluations was not good with respect to the comparative comparative example.
The comparative example is a comparative example 1 in example 1, comparative example 2 in example 2, comparative example 3 in example 3, comparative example 3 in example 4, comparative example 4, comparative examples 5 to 7 and examples. 5 to 6 is Comparative Example 3, and Example 7 is Comparative Example 8.

(3) Test results The test results are shown in Tables 1 to 3. When compared with test solutions containing only component (A) and component (B) (Comparative Examples 1 to 4), or test solutions containing amino acids different from component (C) (Comparative Examples 5 to 7), In the test solutions (Examples 1 to 6) containing the component (C) in addition to the components A) and (B), the color difference and pH change of the test solution are remarkably suppressed, and the odor change is also suppressed. The tendency was seen. Moreover, it turns out that the change of the color and pH of a test liquid is suppressed by adding (C) component also in the test liquid (Comparative Example 8 and Example 7) which used the glycoside as (B) component.

[Test Example 2: Measurement of color difference of external preparation 1]
(1) Test solution preparation Each component was weighed according to Table 4, and the test solutions of Example 8 and Comparative Example 9 were prepared. The test solution of Example 8 corresponds to a solution obtained by adding allantoin as the component (C) to the test solution of Comparative Example 9.

The following were used for each component.
Tranexamic acid: (HUNAN DONGTING PHARMACEUTICAL)
Glucan oligosaccharide: BIOECOLIA (manufactured by Solabia)
Pullulan: (Made by Hayashibara)
Allantoin: (Made by Permachem Asia)

(2) Test Method: Evaluation of Coloring by Acceleration Test Each 10 mL of the prepared test solution was filled into a 20 mL glass container, and the color difference of the test solution at 25 ° C. was measured under the following measurement conditions. Thereafter, the test solution was transferred to a constant temperature bath at 70 ° C. and kept warm for one week. One week later, the test solution kept at 70 ° C. was taken out and made constant at 25 ° C., and the color difference was measured and the color was visually evaluated.

(Color difference measurement)
1 mL of the test solution was placed in a glass cell (CM-A97, thickness 2 mm), and the color difference was measured with a spectrocolorimeter CM-5 (manufactured by Konica Minolta Co., Ltd.). The measured value was Δb * when purified water was used as a blank. The change in color difference was calculated by the following formula.
(Change in color difference (Δb value)) = (Measured value of test solution after incubation at 70 ° C. (b value after accelerated test)) − (Measured value of test solution before incubated (b value before accelerated test)) )
The b value is used as an index indicating transparency. Therefore, it shows that coloring is so few that (DELTA) b value is small.

(Visual evaluation)
According to the following scores, the coloring of the test solution after the acceleration test was visually evaluated.
1: Almost not colored 2: Slightly colored 3: Colored 4: Slightly colored 5: Strongly colored

(3) Test results Table 5 shows the test results. The test solution containing allantoin (Example 8) had a smaller Δb value compared to the test solution containing no allantoin (Comparative Example 9), indicating that the test solution was less colored by the accelerated test. Moreover, it was shown that the test liquid containing the allantoin after the acceleration test is less colored by visual evaluation than the test liquid containing no allantoin.

[Test Example 3: Measurement of color difference of external preparation 2]
(1) Preparation of test solution Each component was weighed according to Table 6 to prepare test solutions of Example 9 and Comparative Example 10. The test liquid of Example 9 corresponds to the composition for external use of Comparative Example 10 to which allantoin (C) is added.

The following were used for each component.
Tranexamic acid: (HUNAN DONGTING PHARMACEUTICAL)
Glucan oligosaccharide: BIOECOLIA (manufactured by Solabia)
Allantoin: (Made by Permachem Asia)

(2) Test Method: Evaluation of Coloring by Acceleration Test Each 10 mL of the prepared test solution was filled into a 20 mL glass container, and the color difference of the test solution at 25 ° C. was measured under the following measurement conditions. Thereafter, the test solution was transferred to a constant temperature bath at 60 ° C. and kept warm for one week. One week later, the test solution kept at 60 ° C. was taken out and made constant at 25 ° C., and the color difference was measured and the color was visually evaluated.

(Color difference measurement)
1 mL of the test solution was placed in a glass cell (CM-A97, thickness 2 mm), and the color difference was measured with a spectrocolorimeter CM-5 (manufactured by Konica Minolta Co., Ltd.). The measured value was Δb * when purified water was used as a blank. The change in color difference was calculated by the following formula.
(Change in color difference (Δb value)) = (Measured value of test solution after incubation at 60 ° C. (b value after acceleration test)) − (Measured value of test solution before incubation (b value before acceleration test)) )

(3) Test results Table 7 shows the test results. The test solution containing allantoin (Example 9) had a smaller Δb value compared to the test solution containing no allantoin (Comparative Example 10), indicating that the test solution was less colored by the accelerated test. Moreover, it was shown that the test liquid containing the allantoin after the acceleration test is less colored by visual evaluation than the test liquid containing no allantoin.

Formulation example An external preparation is prepared according to the following formulation. In addition, each numerical value of a prescription example shows weight%.

Formulation Example 1 (Lotion)
Tranexamic acid 2.0
Glucose / sucrose condensate 1.0
N-Capryloyl acylglycine 0.3
1,3-butylene glycol 10.0
1,2-pentanediol 3.0
Polyoxyethylene hydrogenated castor oil 0.1
Hydrolyzed collagen powder 0.01
DOKUDAMI EXTRACT 0.1
2-Methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer 0.5
Hydroxyethyl cellulose 0.1
Sodium hyaluronate 0.05
Succinic acid 0.04
Disodium succinate 0.06
Preservatives (methyl paraoxybenzoate, phenoxyethanol) Appropriate amount of flavoring agent Appropriate amount of purified water Total remaining amount 100% by weight

Formulation example 2 (milky lotion)
Tranexamic acid 2.0
Arbutin 0.1
N-stearoyl-sodium L-glutamate 0.25
Dipropylene glycol 5.0
1,3-butylene glycol 8.0
Concentrated glycerin 3.0
1,2-pentanediol 2.0
Glycerol monostearate 1.0
Carboxyvinyl polymer 0.2
Xanthan gum 0.05
Meadow Foam Oil 5.0
Glyceryl tri-2-ethylhexanoate 5.0
Methylpolysiloxane 1.0
Triethanolamine 0.1
Bilberry leaf extract 0.1
Edelweiss extract 0.1
Sodium hyaluronate 0.2
Chelating agent (sodium edetate) Appropriate amount of flavoring agent Appropriate amount of purified water Total remaining 100%

Formulation Example 3 (Cream)
Tranexamic acid 1.0
Arbutin 3.0
Decanoylproline Na 1.0
1,3-butylene glycol 8.0
Diglycerin 5.0
Hydroxyethylurea 3.0
Polyoxyethylene behenyl ether 0.8
Glycerol monostearate 1.0
Cetostearyl glucoside / cetostearyl alcohol 1.5
Acrylic acid / alkyl methacrylate copolymer 0.2
Meadow Foam Oil 5.0
Squalane 3.0
Methylpolysiloxane 3.0
Behenyl alcohol 0.5
Stearyl alcohol 1.0
Cetanol 1.0
L-Arginine 0.2
Carrot extract 0.1
Chelating agent (sodium edetate) Appropriate amount of preservative (methyl paraoxybenzoate, phenoxyethanol) Appropriate amount of flavoring agent Appropriate amount of purified water Total remaining amount 100% by weight

Claims

An external preparation containing (A) tranexamic acid or a salt thereof, (B) a saccharide, and (C) a compound represented by formula (I) or a salt thereof.

[In the formula (I), R a represents a linear alkyl group having 7 to 19 carbon atoms or a group represented by —NR d R e , wherein R d and R e each independently represents a hydrogen atom, Or an alkyl group which may have a substituent, and R b and R c are each independently a hydrogen atom, an alkyl group which may have a substituent, or a group represented by the formula (II) R b and R c may be bonded to each other to form a ring, and the substituent is a hydroxyl group, a carboxy group, an alkyl group, or a group represented by the formula (III) Yes,

In formula (II), R f represents a hydrogen atom or an alkyl group which may be substituted with a hydroxyl group.
The external preparation according to claim 1, wherein the compound represented by the formula (I) is a compound represented by the formula (1).

(Wherein R 1 represents any of the groups represented by formulas (2) to (23), and n represents an integer of 6 to 18)
The external preparation according to claim 1, wherein the compound represented by the formula (I) is a compound represented by the formula (24).

(Wherein, R b, R c, R d and R e have the same meanings as R b, R c, R d and R e in the formula (I).)
The component (C) is at least one selected from the group consisting of N-capryloyl acylglycine, N-decanoyl-L-proline, N-stearoyl-L-glutamic acid, allantoin and alcloxa, and salts thereof. The external preparation of Claim 1.
The external preparation according to any one of claims 1 to 4, wherein the component (B) is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, and glycosides.