WO2015046389A1

WO2015046389A1 - Composition for external application to skin containing novel benzylidene azolidine derivative or salt thereof

Info

Publication number: WO2015046389A1
Application number: PCT/JP2014/075545
Authority: WO
Inventors: 清水　崇; 小林　洋介; 陽子水垂; 雅俊羽賀
Original assignee: ロート製薬株式会社
Priority date: 2013-09-27
Filing date: 2014-09-26
Publication date: 2015-04-02
Also published as: JP2015086224A; TW201601769A; JP5799148B2

Abstract

The present invention relates to providing a composition for external application to the skin, wherein a benzylidene azolidine derivative or a salt thereof has improved photostability, said benzylidene azolidine derivative being a novel neutral compound that is hydrophilic and safe to the skin, while having an ultraviolet absorbing effect (especially an UVA absorbing effect). A composition for external application to the skin, which is characterized by containing a benzylidene azolidine derivative represented by general formula (I) or a salt thereof and at least one substance selected from the group consisting of an ultraviolet absorbent, an antioxidant, a skin whitening component, an anti-inflammatory component and a thickening component. (In structural formula (I), n represents an integer of 1-5; A¹ represents O, S or N-A⁴; and each of A², A³ and A⁴ independently represents a hydrogen atom, a C₁-C₈ alkyl group which may be substituted by a hydroxyl group, or the like (provided that one or more hydroxyl groups are contained in at least one of A², A³ and A⁴).)

Description

Skin external composition containing novel benzylidene azolidine derivatives or salts thereof

The present invention relates to an external composition for skin containing a novel benzylidene azolidine derivative or a salt thereof. More specifically, the present invention relates to a novel benzylidene azolidine derivative or a salt thereof, and at least one selected from the group consisting of an ultraviolet absorber, an antioxidant, a whitening active ingredient, an anti-inflammatory ingredient, and a thickening ingredient. The present invention relates to an external composition for skin containing seeds.

UV rays are essential for the biosynthesis of vitamin D, and are used to promote blood circulation and metabolism in the living body, and also for sterilization and disinfection. On the other hand, if the skin is exposed to ultraviolet rays excessively, it may cause skin cancer or promote aging of the skin, causing spots, freckles and wrinkles. Furthermore, when various synthetic resins or paints such as polyethylene, polypropylene, PVC, and ABS resin are excessively exposed to ultraviolet rays, these synthetic resins and paints are deteriorated. Thus, excessive exposure to ultraviolet light can cause adverse effects.

Therefore, in order to prevent such adverse effects, various ultraviolet absorbers have been developed and widely used.

Note that near ultraviolet rays, which are generally referred to as “ultraviolet rays (UV)”, are largely divided into UVA (wavelength 315 to 400 nm), UVB (wavelength 280 to 315 nm), and UVC (wavelength 200 to 280 nm) based on the wavelength. Separated. In addition, although UVC is UV derived from sunlight, since it absorbs remarkably in the ozone layer or the like by the time it reaches the ground, it usually cannot pass through the ozone layer or the like and reach the ground.

UVA and UVB are mainly responsible for the occurrence of skin cancer, skin aging, and deterioration of synthetic resins and paints.

Therefore, the ultraviolet absorber has been developed mainly for the purpose of absorbing UVA or UVB.

Examples of ultraviolet absorbing substances contained in conventionally developed ultraviolet absorbers include isooctyl p-methoxycinnamate, isoamyl p-methoxycinnamate, phenylbenzimidazole Na sulfonate, 3- (4′-methylbenzylidene) -camphor, 4-t-butyl-methoxy-dibenzoylmethane and 4-isopropyl-dibenzoylmethane are known. These compounds all have an aromatic ring. The electrons conjugated in the aromatic ring can be excited with less energy than the electrons that are not conjugated, and can absorb ultraviolet rays. Further, when the conjugated system is expanded, conjugated electrons can be excited with smaller energy, and can absorb ultraviolet rays on the long wavelength side, visible light, and the like.

In addition, many UVB absorbing compounds that can be put to practical use have been developed. As such UVB absorbing compounds, for example, the above-mentioned isooctyl p-methoxycinnamate, isoamyl p-methoxycinnamate, phenylbenzimidazole Na sulfonate, and 3- (4′-methylbenzylidene) -camphor are known. .

On the other hand, many of the conventional UVA absorbing compounds are decomposed in the process of absorbing UVA and converting the UVA light energy into thermal energy and releasing it. That is, conventional UVA absorbing compounds have a problem in light stability, and there are still few compounds that have solved such problems.

For example,

Patent Documents

1 and 2 disclose hydantoin derivatives as currently developed UVA absorbing compounds.

By the way, when an external composition for skin, such as a sunscreen composition, is used in a situation where the application site is in contact with water, such as a sea bath, the composition for external use on the skin is not affected even if the application site is in contact with water. There is a need for properties that remain in application. Therefore, it is preferable that the UVA absorbing compound contained in such a composition has high oil solubility.

On the other hand, in recent years, as the effects of ultraviolet rays on the skin become clear, the composition for external use of skin, such as a sunscreen composition, is not used in daily life (that is, not necessarily in a situation where the application site is in contact with water). Even). In such a mode of use, there is no stickiness, film feeling, white residue, etc. during use, and it is required that the composition can be easily washed away from the application site after use (excellent detergency). High hydrophilicity is also required for UVA-absorbing compounds contained in products.

In order to use such a composition for external use on the skin, the hydantoin derivatives disclosed in

Patent Documents

1 and 2 have poor hydrophilicity, and it has been difficult to make these functions compatible with an external composition containing the derivative. .

Thus, the conventional hydantoin derivatives have room for improvement in that they cannot exhibit excellent hydrophilicity as well as high ultraviolet (in particular, UVA) absorption.

In particular, when used as a skin external preparation such as a sunscreen agent, the light-absorbing substance itself is required to have light stability over time.

Japanese Patent Laid-Open No. 02-111760 Japanese Patent No. 3497246

In light of such circumstances, the present invention provides the photostability of benzylidene azolidine derivatives and salts thereof, which are hydrophilic and skin-neutral neutral compounds having an ultraviolet absorption effect (particularly UVA absorption effect). An object is to provide an improved skin external composition.

The present invention also provides an external composition for skin having improved ultraviolet absorption of a benzylidene azolidine derivative and a salt thereof, which is a novel neutral compound that is UV-absorbing (particularly UVA-absorbing), hydrophilic and safe for the skin. The purpose is to provide.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have succeeded in creating a novel benzylidene azolidine derivative or a salt thereof shown below, and the above compound, an ultraviolet absorber, an antioxidant, a whitening active ingredient, It has been found that the object can be achieved by a composition for external use of skin comprising an anti-inflammatory component and at least one selected from the group consisting of thickening components, and the present invention has been completed.

That is, the external composition for skin of the present invention comprises a benzylidene azolidine derivative represented by the general formula (I) or a salt thereof,

(In the structural formula (I), n is an integer of 1 to 5, A ¹ is O, S, or NA ⁴ , and A ² , A ^3, and A ⁴ are each independently hydrogen An atom, an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group, a functional group (1) represented by the following structural formula (1), a functional group (2) represented by the following structural formula (2), Or a functional group (3) represented by the following structural formula (3) (provided that at least one of A ² , A ³ and A ⁴ contains one or more hydroxyl groups), and n is 2 In the case of an integer of ˜5, a plurality of A ³ —O— may be the same or different.)

(In Structural Formula (1), X ¹ is an alkylene group having 2 to 4 carbon atoms, R ¹ is a hydroxyalkyl group having 2 to 4 carbon atoms, and m is an integer of 1 to 4. When m is an integer of 2 to 4, a plurality of X ¹ may be the same or different.)

(In Structural Formula (2), X ² is an alkylene group having 2 to 4 carbon atoms, R ² is a hydroxyalkyl group having 2 to 4 carbon atoms, p is 1 or 2, and q is 0 And when q is an integer of 2 to 4, a plurality of X ² may be the same or different.)

(In Structural Formula (3), X ^3a and X ^3b are each independently an alkylene group having 2 to 4 carbon atoms, and R ^3a and R ^3b are each independently a hydroxyalkyl having 2 to 4 carbon atoms. And r is 1 or 2, and s and t are each independently an integer of 0 to 4. When s is an integer of 2 to 4, a plurality of X ^3a are the same or different And when t is an integer of 2 to 4, a plurality of X ^3b may be the same or different.)
And
It is characterized by containing at least 1 sort (s) chosen from the group which consists of a ultraviolet absorber, an antioxidant, a whitening active ingredient, an anti-inflammatory ingredient, and a thickening ingredient.

The composition for external use of the skin of the present invention is at least one selected from the group consisting of the above-mentioned benzylidene azolidine derivative or a salt thereof, an ultraviolet absorber, an antioxidant, a whitening active ingredient, an anti-inflammatory ingredient, and a thickening ingredient. The composition for external use on the skin with improved light stability of the benzylidene azolidine derivative or a salt thereof can be obtained.

Further, the composition for external use of the skin of the present invention is a composition for external use of skin, which comprises the benzylidene azolidine derivative or a salt thereof and an ultraviolet absorber, thereby improving the ultraviolet absorption effect of the benzylidene azolidine derivative or a salt thereof. It becomes.

The present invention also includes a method for stabilizing the above-mentioned benzylidene azolidine derivative or a salt thereof contained in an external composition for skin and a method for improving the ultraviolet absorption effect.

In the skin external composition of the present invention, in the structural formula (I), at least one of A ² , A ³ and A ⁴ is the functional group (1), the functional group (2), or the above It is preferable that it is a functional group (3).

In the composition for external use of the skin of the present invention, in the structural formula (I), A ² and / or A ³ is a C 1-8 alkyl group substituted with a hydrogen atom or a hydroxyl group, the functional group It is preferable that it is (1), the said functional group (2), or the said functional group (3).

In the skin external composition of the present invention, the structural formula (I) is preferably a benzylidene azolidine derivative represented by the following structural formula (II) or a salt thereof.

(In Structural Formula (II), n ′ is an integer of 0 to 4, and when n ′ is an integer of 1 to 4, a plurality of A ³ —O— may be the same or different. )

In the skin external composition of the present invention, the structural formula (I) is preferably a benzylidenehydantoin derivative represented by the following structural formula (III) or a salt thereof.

Further, in the composition for external use of the skin of the present invention, the ultraviolet absorber (ultraviolet absorbing component) is cinnamic acid derivative, benzoic acid derivative, salicylic acid derivative, benzophenone derivative, benzylidene camphor derivative, triazine derivative, phenylbenzimidazole derivative, phenylbenzoic acid. One or more selected from the group consisting of a triazole derivative, anthranyl derivative, imidazolidine derivative, benzalmalonate derivative, dibenzoylmethane derivative, and 4,4-diarylbutadiene derivative are preferable.

Among them, the ultraviolet absorber is 2-methoxyhexyl paramethoxycinnamate, ferulic acid, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 3,3′-carbonylbis [4-hydroxy- 6-methoxybenzenesulfonic acid] disodium, hydroxymethoxybenzophenonesulfonic acid (benzophenone-1), α-cyano-β-phenylcinnamic acid 2-ethylhexyl (octocrylene), phenylbenzimidazolesulfonic acid, terephthalylidene dicanfursulfonic acid Dimethicodiethylbenzalmalonate, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine 2,4,6-tris [4-2-ethyl (Hexyloxycarbonyl) anilino] -1,3,5-triazine, 4-tert-butyl-4′-methoxydibenzoylmethane and 2,2′-methylenebis [6- (2H-benzotriazol-2-yl) One or more selected from the group consisting of -4- (1,1,3,3-tetramethylbutyl) phenol] is preferred. Moreover, when it can take the form of a salt, the salt of any of the said compounds and the salt of any of the said derivatives may be sufficient.

In the composition for external use of the skin of the present invention, the antioxidant (also referred to as an antioxidant component or an antioxidant component) is a vitamin-based antioxidant, a sulfur-containing antioxidant, a phenol-based antioxidant, or a polyphenol-based agent. One or more selected from the group consisting of antioxidants are preferred.

Among them, the antioxidant is pyrroloquinoline quinone and derivatives thereof, bisethylhexylhydroxydimethoxybenzyl malonate and derivatives thereof, diethylhexylcillinylidentocopherol and derivatives thereof, thiotaurine and derivatives thereof, dibutylhydroxytoluene and derivatives thereof. , Gallic acid and derivatives thereof, chlorogenic acid and derivatives thereof, hesperidin and derivatives thereof, glucosyl hesperidin and derivatives thereof, ergothioneine and derivatives thereof, flavonoids and derivatives thereof, dibutylhydroxyanisole and derivatives thereof, and salt forms In this case, it is preferably at least one selected from the group consisting of a salt of any one of the compounds and a salt of any one of the derivatives.

In the skin external composition of the present invention, the whitening active ingredient (whitening agent) is a tyrosinase inhibitor, an endothelin-1 receptor inhibitor, a tyrosinase proteolysis promoter, a melanin excretion promoter, and a melanin transport inhibitor. It is preferable that it is 1 or more types selected from the group which consists of.

Among them, the whitening active ingredient (whitening agent) is ascorbic acid and its derivatives or salts thereof, hydroquinone and its derivatives or salts thereof, tranexamic acid and its derivatives or salts thereof, ellagic acid, and niacin. It is preferably at least one selected from the group consisting of amides.

In the composition for external use of the skin of the present invention, the anti-inflammatory component (anti-inflammatory agent) is allantoin, calamine, glycyrrhizic acid and a derivative thereof or a salt thereof, glycyrrhetinic acid and a derivative or a salt thereof, zinc oxide, guaiazulene It is preferably one or more selected from the group consisting of pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, and salicylic acid.

Among them, the anti-inflammatory component (anti-inflammatory agent) is allantoin, glycyrrhizic acid and derivatives thereof or salts thereof, glycyrrhetinic acid and derivatives or salts thereof, pyridoxine hydrochloride, menthol, camphor, indomethacin, and salicylic acid. More preferably, it is at least one selected from the group consisting of:

In the composition for external use of the skin of the present invention, the thickening component (thickener) is an acrylic acid thickener, vinyl thickener, cellulose thickener, mucopolysaccharide thickener, amino acid. It should be at least one selected from the group consisting of thickeners, seaweed thickeners, microbial thickeners, polyethylene glycol thickeners, starch thickeners, and plant thickeners. Is preferred.

Among them, the thickening component (thickener) is acrylic acid / alkyl methacrylate copolymer, hydroxyethyl acrylate / acryloyldimethyltaurine salt copolymer, sodium acrylate / acryloyldimethyltaurine copolymer, (acrylic) Acid / acryloyldimethyltaurine / dimethylacrylamide) crosspolymer, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, polyethylene glycol, dimethyldistearylammonium hectorite, (acryloyldimethyltaurine ammonium / vinylpyrrolidone) copolymer, polyacrylic acid or its Derivatives and their salts, polyvinyl alcohol, xanthan gum, and hydroxypropyl starch phosphate There it is preferable.

The external composition for skin of the present invention comprises at least one selected from the group consisting of an ultraviolet absorber, an antioxidant, a whitening active ingredient, an anti-inflammatory ingredient, and a thickening ingredient. However, the ultraviolet absorber, the antioxidant, the whitening active ingredient, the anti-inflammatory ingredient, and the thickening ingredient are also included in the case of using a combination of them as appropriate. In addition, the above ultraviolet absorbers, antioxidants, whitening active ingredients, anti-inflammatory ingredients, and thickening ingredients are added and used mainly for utilizing other properties and characteristics different from the above-mentioned ultraviolet absorbing action, etc. Even if it is blended, it is included in the external composition for skin of the present invention.

The composition for external use of the skin of the present invention improves the photostability of a benzylidene azolidine derivative and a salt thereof, which is a novel hydrophilic and skin-neutral neutral compound having an ultraviolet absorbing action (particularly UVA absorbing action). be able to.

In addition, the composition for external use of the skin of the present invention has an ultraviolet absorption effect of a benzylidene azolidine derivative and a salt thereof, which is a neutral hydrophilic new compound having an ultraviolet absorption action (particularly UVA absorption action) and safe for the skin. Can be improved.

The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example. The graph which shows the measurement result of the light absorbency of the ultraviolet-ray in an Example.

Hereinafter, embodiments of the present invention will be described in detail.

[Benzylidene azolidine derivatives and salts thereof]
The benzylidene azolidine derivative in the present invention is represented by the following structural formula (I).

In the above structural formula (I), the moiety represented by the following structural formula (i) and the moiety represented by the following structural formula (ii) are respectively represented by “benzene ring part (i)” and “azolidine moiety ( ii) ".

As shown in the structural formula (I) above, the azolidine moiety (ii) includes “NA ² ”, and further, when A ¹ is “NA ⁴ ”, “NA ⁴ ” is include. The nitrogen atom of “NA ² ” or “NA ⁴ ” is a basic nitrogen atom, and an inorganic acid or organic acid can be added to this N atom to form an acid addition salt. Here, examples of the inorganic acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, and the like. Examples of the organic acid include acetic acid, citric acid, gluconic acid, tartaric acid, fumaric acid, maleic acid, lactic acid, methanesulfonic acid, and paratoluenesulfonic acid.

Also, the salt of the benzylidene azolidine derivative in the present invention is preferable in that the hydrophilicity is improved and the handling becomes easy because it tends to be solid, compared to the benzylidene azolidine derivative in the present invention.

In the structural formulas in this specification excluding the structural formula (I) and the structural formula (I), “n”, “A ¹ ”, “A ² ”, and “A ³ ” are as follows: Stipulated in

(1) “n”
n is an integer of 1 to 5, and is preferably an integer of 1 to 3 from the viewpoint of exhibiting high specific absorbance (absorbance of ultraviolet rays per mass) and exhibiting high UV absorption. Preferably it is 1.

(2) “A ¹ ”
A ¹ represents, O, S, or ^{N-A 4,,} UVA and, from the viewpoint of effectively absorbing light in the wavelength region close to the UVA, preferably a ^{N-A 4.}

(3) “A ² ”, “A ³ ”, and “A ⁴ ”
A ² , A ³ and A ⁴ each independently represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group, or a functional group (functional group represented by the following structural formula (1) (1)), a functional group represented by the following structural formula (2) (functional group (2)), or a functional group represented by the following structural formula (3) (functional group (3)). However, at least one of A ² , A ^3, and A ⁴ includes one or more hydroxyl groups.

Also, in that it can improve the UV ^absorbing, A 2, ^{A 3} and, among the ^{A 4,} at least one said functional group (1), the functional group (2), or the functional groups (3) It is preferable that at least two of A ² , A ^3, and A ⁴ are the functional group (1), the functional group (2), or the functional group (3).

(In Structural Formula (3), X ^3a and X ^3b are each independently an alkylene group having 2 to 4 carbon atoms, and R ^3a and R ^3b are each independently a hydroxyalkyl having 2 to 4 carbon atoms. And r is 1 or 2, and s and t are each independently an integer of 0 to 4. When s is an integer of 2 to 4, a plurality of X ^3a are the same or different And when t is an integer of 2 to 4, a plurality of X ^3b may be the same or different.)

When n is an integer of 2 to 5, a plurality of A ³ —O— may be the same or different.

Further, from the viewpoint of exhibiting high water solubility, at least one of A ¹ , A ² and “A ³ —O—” is preferably a functional group having a hydroxyl group.

(3-1) “Alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group”
The “alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group” may be linear or branched as long as it is an alkyl group having 1 to 8 carbon atoms. Even if it is substituted with (hydroxyalkyl group), it may be an alkyl group not substituted with a hydroxyl group. Among these, from the viewpoint of improving UV absorption and water hydrophilicity, it is preferably a linear or branched hydroxyalkyl group having 1 to 8 carbon atoms.

In addition, the number of carbon atoms of the alkyl group is preferably 1 to 8, and more preferably 1 to 4, from the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited.

(3-2) "Functional group (1)"
The functional group (1) is a functional group represented by the structural formula (1). Here, X ¹ is an alkylene group having 2 to 4 carbon atoms, and the alkylene group may be linear or branched. From the viewpoint that X ¹ can exhibit a high specific absorbance (absorbance of ultraviolet rays per mass), the alkylene group has 1 to 2 carbon atoms (for example, the alkylene group is a methylene group (—CH ₂ —)). Or an ethylene group (—CH ₂ CH ₂ —)) is preferable.

R ¹ is a hydroxyalkyl group having 2 to 4 carbon atoms (an alkyl group substituted with at least one hydroxyl group), can exhibit high specific absorbance (absorbance of ultraviolet rays per mass), and is produced from a general-purpose reagent raw material. In view of the possibility, it is preferably a hydroxyalkyl group having 2 carbon atoms, more preferably a hydroxyethyl group (—CH ₂ CH ₂ OH).

m is an integer of 1 to 4, and is preferably an integer of 1 to 2 from the viewpoint that it can exhibit high specific absorbance (absorbance of ultraviolet rays per mass) and can be produced from a general-purpose reagent raw material. 1 is more preferable.

When m is an integer of 2 to 4, a plurality of X ¹ may be the same or different. In this case, from the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited and it can be produced from a general-purpose reagent raw material, a plurality of X ¹ is a methylene group (—CH ₂ —) or an ethylene group ( —CH ₂ CH ₂ —) is preferred.

(3-3) "Functional group (2)"
The functional group (2) is a functional group represented by the structural formula (2). Here, X ² is an alkylene group having 2 to 4 carbon atoms, and the alkylene group may be linear or branched. From the viewpoint that X ² can exhibit a high specific absorbance (absorbance of ultraviolet rays per mass) and can be produced from a general-purpose reagent raw material, the alkylene group has 1 to 2 carbon atoms (for example, an alkylene group). Is preferably a methylene group (—CH ₂ —) or an ethylene group (—CH ₂ CH ₂ —)).

R ² is a hydroxyalkyl group having 2 to 4 carbon atoms (an alkyl group substituted with at least one hydroxyl group), can exhibit high specific absorbance (absorbance of ultraviolet rays per mass), and is manufactured from a general-purpose reagent raw material. In view of the possibility, it is preferably a hydroxyalkyl group having 2 carbon atoms, more preferably a hydroxyethyl group (—CH ₂ CH ₂ OH).

P is 1 or 2, and is preferably 1 from the viewpoint of exhibiting high specific absorbance (absorbance of ultraviolet rays per mass).

q is an integer of 0 to 4, and is preferably an integer of 1 to 2 from the viewpoint that it can exhibit high specific absorbance (absorbance of ultraviolet rays per mass) and can be produced from a general-purpose reagent raw material. 1 is more preferable.

When q is an integer of 2 to 4, a plurality of X ¹ may be the same or different. In this case, from the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited and it can be produced from a general-purpose reagent raw material, a plurality of X ¹ is a methylene group (—CH ₂ —) or an ethylene group ( —CH ₂ CH ₂ —) is preferred.

(3-4) "Functional group (3)"
The functional group (3) is a functional group represented by the structural formula (3). Here, X ^3a and X ^3b are each independently 2 to 4 alkylene groups, and the alkylene groups may be linear or branched. From the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited, X ^3a and X ^3b are each independently an alkylene group having 2 to 4 carbon atoms (for example, an alkylene group is a methylene group (-CH _2- ) or an ethylene group (—CH ₂ CH ₂ —) is preferred.

R ^3a and R ^3b are each independently a hydroxyalkyl group having 2 to 4 carbon atoms (an alkyl group substituted with at least a hydroxyl group), and can exhibit high specific absorbance (absorbance of ultraviolet rays per mass) and From the viewpoint that it can be produced from a general-purpose reagent raw material, it is preferably a hydroxyalkyl group having 2 carbon atoms, more preferably a hydroxyethyl group (—CH ₂ CH ₂ OH).

R is 1 or 2, and is preferably 1 from the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited.

s and t are each independently an integer of 0 to 4, and can exhibit high specific absorbance (absorbance of ultraviolet rays per mass) and can be produced from a general-purpose reagent raw material. It is preferably an integer, and more preferably 1.

When s is an integer of 2 to 4, a plurality of X ^3a may be the same or different, and when t is an integer of 2 to 4, the plurality of X ^3b is the same or different. It may be. In this case, from the viewpoint of exhibiting high specific absorbance (absorbance of ultraviolet rays per mass) and being able to be produced from a general-purpose reagent raw material, a plurality of X ^3a and X ^3b are methylene groups (—CH ₂ —). Alternatively, an ethylene group (—CH ₂ CH ₂ —) is preferable.

(3-5) “A ² ”
From the viewpoint of further improving hydrophilicity, A ² represents a hydrogen atom, a hydroxyl alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, a functional group (1), a functional group (2) or a functional group (3 It is preferably a hydroxyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, more preferably a functional group (1), a functional group (2) or a functional group (3), More preferably, it is 1) or functional group (3).

(3-6) “A ³ ”
As described above, A ³ is any one of a hydrogen atom, an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group, and functional groups (1) to (3). “A ³ —O—” bonded to (i) is an electron donating group. Therefore, when UV is irradiated to the benzylidene azolidine derivative or a salt thereof in the present invention represented by the above structural formula (I), electrons are donated from “A ³ —O—” to the benzene ring by the resonance effect, The conjugated system of the benzene ring is effectively expanded. Therefore, the benzylidene azolidine derivative or a salt thereof in the present invention has good UV absorption of long-wave ultraviolet light (for example, UVA).

From the viewpoint that UV absorption can be further improved, A ³ is a hydrogen atom, a hydroxyalkyl group having 1 to 8 carbon atoms, a functional group (1), a functional group (2), or a functional group (3). The functional group (1) or the functional group (3) is more preferable.

Furthermore, from the viewpoint that UV absorption can be further improved, “A ³ —O—” is bonded to the para-position of the benzene ring portion (i) with respect to the “azolidine portion (ii)”. preferable. Such a benzylidene azolidine derivative is represented by the following structural formula (II).

(In the above structural formula (II), n ′ is an integer of 0 to 4, and when n ′ is an integer of 1 to 4, a plurality of A ³ —O— may be the same or different. A ³ is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms and substituted with a hydroxyl group, a functional group (1), a functional group (2), or a functional group (3).

Here, from the viewpoint that UV absorption and hydrophilicity can be further improved, n ′ in the structural formula (II) is 0 and A ¹ is NA ⁴ , that is, the present invention. The benzylidene azolidine derivative is preferably represented by the following chemical structural formula (III).

In consideration of ease of synthesis (shortening of the synthesis process), A ² and A ³ are more preferably the same functional group.

(3-7) “A ⁴ ”
A ⁴ is preferably a hydrogen atom or a functional group (3), more preferably a hydrogen atom, from the viewpoint that UV absorption and hydrophilicity can be further improved.

(4) Molecular weight From the viewpoint that high absorbance and high safety can be exhibited in a balanced manner, the molecular weight of the benzylidenehydantoin derivative in the present invention is usually 250 to 1000, preferably 300 to 500. The molecular weight is preferably 300 or more in order to reduce the risk of adverse effects such as irritation and toxicity through the skin and absorbed into the body.

In the composition for external use of the skin of the present invention, the content of the benzylidene azolidine derivative or a salt thereof can be 0.00001 wt% or more and 20 wt% or less, and 0.0001 wt% or more and 10 wt% or less. % By weight or less, 0.001% to 5% by weight, 0.05% to 3% by weight, 0.03% to 1% by weight Or 0.02 wt% or more and 0.5 wt% or less, or 0.01 wt% or more and 0.1 wt% or less.

[Method for producing benzylidene azolidine derivative and salt thereof]
For example, first, as shown in the chemical reaction formula (1), a compound (a) represented by the following formula (a) and a compound (b) represented by the following formula (b) are mixed in the presence of a base. To synthesize a compound (c) represented by the following formula (c). Next, as shown in the chemical reaction formula (2), by reacting the compound represented by the following formula (c) with the compound (d) represented by the following formula (d) in the presence of a base, The benzylidene azolidine derivative in the present invention can be synthesized.

Here, as the compound (b), a commercially available product can be used as it is. A compound (b) having a functional group excluding a hydrogen atom as A ³ is represented by the following structural formula (b ′), and a compound (b ′) having a hydrogen atom as A ³ and the following structural formula (e) As shown in the reaction formula (3), a compound obtained by reacting the compound (e) represented by the formula (e) with a base can be used.

In addition, as the compound (a), a commercially available product can be used as it is.

Further, as shown by the following formula (4-1), the compound (a) and the compound (d) are reacted in the presence of a base to give a compound represented by the following structural formula (f) ( f) can be synthesized. Alternatively, as shown in the following reaction formula (4-2), the following compound (g) and the following compound (h) are used in the presence or absence of a base, using a condensing agent, and the presence of an acid. The compound (f) represented by the following structural formula (f) can also be synthesized by cyclization below. Here, when A ¹ of the compound (a) is “NH”, as shown in the reaction formula (5), the compound (f) and the following structural formula (e ′) are combined in the presence of a base. By reacting, compound (f) in which A ¹ is “NA ⁴ ” can be synthesized. Next, as shown in the following reaction formula (6), the benzylidene azolidine derivative in the present invention can be synthesized by reacting the compound (f) with the compound (b) in the presence of a base. .

^{(A 1} of formula (g) is the same as ^{A 1} of formula (I).
Z is a hydroxyl group or an alkoxyl group. )

^{(A 2} of the formula (h) are the same and ^{A 2} in formula (I).)

When the benzylidene azolidine derivative in the present invention has a functional group (2) or a functional group (3) as A ² , A ³ and A ^{4 in} the structural formula (I), the compound (d), Instead of the compound (e) and the compound (e ′), the compound (i) represented by the following structural formula (i), and the following structural formula (j) instead of the compound (h) In the same manner as in the reaction formulas (1) to (6) except that the compound (j) is used, in the structural formula (I), A ² , A ³ or A ⁴ is represented by the following structural formula (k The compound (k) having a functional group (k) represented by) can be synthesized. Next, the compound (k) may be led to the benzylidene azolidine derivative in the present invention by a general functional group conversion reaction (esterification of carboxylic acid, amidation of carboxylic acid, transesterification, amidation of ester, etc.). it can.

(Y in formula (i) is the same as Y in formula (d), u is 1 or 2, and Z is a hydroxyl group or an alkoxyl group.)

(U in the formula (j) is 1 or 2, and Z is a hydroxyl group or an alkoxyl group.)

(U in the formula (k) is 1 or 2, and Z is a hydroxyl group or an alkoxyl group.)

Examples of the base used in the method for producing the benzylidene azolidine derivative in the present invention as described above include sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium t-butoxide, potassium t-butoxide, pyridine, and triethylamine. , Triisopropylamine, diisopropylethylamine, pyrrolidine, piperidine, sodium acetate, aqueous ammonia, diazabicycloundecene and diazabicyclononene.

Examples of the condensing agent used in the method for producing a benzylidene azolidine derivative in the present invention include phosgene, triphosgene, carbonyldiimidazole, trichloromethyl chloroformate, paranitrophenyl chloroformate, and paracyanophenyl chloroformate. .

Examples of the acid used in the method for producing a benzylidene azolidine derivative in the present invention include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, or acetic acid, citric acid, gluconic acid, tartaric acid, fumaric acid. Examples thereof include organic acids such as acid, maleic acid, lactic acid, methanesulfonic acid, and paratoluenesulfonic acid.

Further, the benzylidene azolidine derivative obtained as described above can be treated with an adsorbent such as silica gel, alumina, zeolite, activated carbon, ion exchange resin, porous synthetic resin, evaporation of the solvent, and / or recrystallization. A highly purified product can be obtained by purifying by the above.

Further, the salt of the benzylidene azolidine derivative in the present invention is obtained by adding an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid or the like, acetic acid, citric acid to the benzylidene azolidine derivative obtained as described above. It can be obtained by adding an organic acid such as gluconic acid, tartaric acid, fumaric acid, maleic acid, lactic acid, methanesulfonic acid, paratoluenesulfonic acid, etc., neutralizing, distilling, and purifying.

[Ultraviolet absorber]
As the ultraviolet absorber (ultraviolet absorbing component) in the present invention, a known ultraviolet absorber can be used as long as the effects of the present invention are not impaired. In the present invention, the ultraviolet absorber (ultraviolet absorbing component) refers to a compound (component) having a property of absorbing ultraviolet rays.

As the ultraviolet absorber, for example,
(A) 2-methoxyhexyl paramethoxycinnamate, isopropyl methoxycinnamate, α-cyano-β-phenylcinnamate 2-ethylhexyl (octocrylene), diisopropyl methylcinnamate, methylbis (trimethylsiloxy) silylisopentyl trimethoxycinnamate, Cinnamic acid derivatives such as methyl 2,5-diisopropylcinnamate, glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, cinoxalate, DEA methoxycinnamate, ferulic acid, and isoamyl methoxycinnamate;
(B) Para-aminobenzoic acid (hereinafter abbreviated as “PABA”), ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, glyceryl PABA, PEG-25PABA, paradimethylaminobenzoic acid amyl, paradimethylamino Benzoic acid derivatives such as 2-ethylhexyl benzoate and 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester;
(C) salicylic acid derivatives such as homosalate, ethylhexyl salicylate, TEA salicylate, ethylene glycol salicylate, and dipropylene glycol salicylate;
(D) Dihydroxybenzophenone (benzophenone-1), tetrahydroxybenzophenone (benzophenone-2), 2-hydroxy-4-methoxybenzophenone (benzophenone-3), hydroxymethoxybenzophenonesulfonic acid (benzophenone-4), dihydroxydimethoxybenzophenone (benzophenone) -5), dihydroxydimethoxybenzophenone (benzophenone-6), 2,2'-dihydroxy-4-methoxybenzophenone (benzophenone-8), and 3,3'-carbonylbis [4-hydroxy-6-methoxybenzenesulfonic acid Benzophenone derivatives such as disodium (benzophenone-9);
(E) benzylidene camphor derivatives such as 3-benzylidene camphor, 4-methylbenzylidene camphor, benzylidene camphor sulfonic acid, terephthalidene di camphor sulfonic acid, camphor benzalkonium methosulfate, and polyacrylamide methyl benzylidene camphor;
(F) Anisotriazine, diethylhexylbutamide triazone, 2,4,6-tris (diisobutyl-4′-aminobenzalmalonate) -s-triazine, 2,4-bis-[{4- (2- Ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine and 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] Triazine derivatives such as -1,3,5-triazine;
(G) phenylbenzimidazole derivatives such as phenylbenzimidazolesulfonic acid and disodium phenyldibenzimidazole tetrasulfonate;
(H) Drometrizol trisiloxane and 2,2′-methylenebis [6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol] Phenylbenzotriazole derivatives;
(I) anthranyl derivatives such as menthyl anthranilate;
(J) imidazolidine derivatives such as dimethoxybenzylideneoxoimidazolidinepropionate 2-ethylhexyl;
(K) benzalmalonate derivatives such as dimethicodiethylbenzalmalonate;
(L) 4,4-diarylbutadiene derivatives such as 1,1-dicarboxy (2,2′-dimethylpropyl) -4,4-diphenylbutadiene; and (m) 4-tert-butyl-4′-methoxydi Dibenzoylmethane derivatives such as benzoylmethane;
Etc. These compounds may be used alone or in combination of two or more. These may be used singly or in combination of two or more.

Among them, in order to absorb ultraviolet rays in a wide wavelength range and increase the usefulness as a cosmetic raw material, a UV-A wave absorber and a UV-B wave absorber are used in combination, or a UV-AB wave absorber is used. It is preferable to use it. The benzylidene azolidine derivative or a salt thereof in the present invention often has a UVA absorption action in particular, but a UV-A wave absorber and / or a UV-B wave absorber may be appropriately used in combination.

Examples of the UV-A wave absorber include, but are not limited to, for example, terephthalylidene dihydrogen sulfonic acid, dimethoxybenzylideneoxoimidazolidinepropionate 2-ethylhexyl (for example, soft shade DH (trade name); manufactured by Ajinomoto Co., Inc.) Hexyl 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoate (for example, ubinal A plus (trade name); manufactured by BASF), and 4-tert-butyl-4′-methoxydibenzoylmethane ( For example, Pulsol 1789 (trade name); manufactured by DSM Nutrition Japan Co., Ltd.) can be used.

Examples of the UV-B wave absorber include, but are not limited to, 2-methoxyhexyl paramethoxycinnamate (for example, Pulsol MCX (trade name); DSM Nutrition Japan Co., Ltd., ubinal MC80 (trade name), ubinal MC80N (commodity) Name); manufactured by BASF), isopropyl paramethoxycinnamate, para-aminobenzoic acid, ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, PEG-25PABA (for example, ubinal P25 (trade name); manufactured by BASF) , Homosalate (for example, Pulsol HMS (trade name); manufactured by DSM Nutrition Japan, Usolex HMS (trade name); manufactured by Merck), ethylhexyl salicylate (ethyl hexyl salicylate, salicyl) Also referred to as octyl) (for example, Neo Heliopan OS (trade name); manufactured by Herman and Reimer), 3-benzylidene camphor (for example, Megizolyl SD (trade name); manufactured by Simex), 4-methylbenzylidene camphor (for example, Usolex) 6300 (trade name); manufactured by Merck Ltd.), benzylidene camphor sulfonic acid (eg, Megizolyl SL (trade name); manufactured by Simex Corp.), camphor sulfate benzalkonium methosulfate (eg, megizolyl SO (trade name); manufactured by Simex Corp.) Polyacrylamide methyl benzylidene camphor (for example, Megizolyl SW (trade name); manufactured by Simex), terephthalylidene camphor sulfonic acid (for example, Megizolyl SX (trade name); manufactured by Simex), diethylhexyl butamide tri Zon, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine (for example, ubinal T150 (trade name); manufactured by BASF), phenylbenzimidazolesulfonic acid ( For example, Pulsol HS (trade name); manufactured by DSM Nutrition Japan, Eusolex 232 (trade name); manufactured by Merck), disodium phenyldibenzimidazole tetrasulfonate (for example, Neo Heliopan AP (trade name); Herman And Reimer, Inc. Dimethicodiethylbenzalmalonate (for example, Pulsol SLX (trade name); manufactured by DSM Nutrition Japan), and α-cyano-β-phenylcinnamic acid 2-ethylhexyl (octocrylene) (for example, ubinal 539N ( Product ); BASF Corporation; Esca roll 597 (trade name); ISP Japan Co., Ltd., Eusolex OCR (trade name); manufactured by Merck & Co., Inc., Parsol 340 (trade name); it is possible to increase the DSM Nutrition Japan), and the like.

Examples of the UV-AB wave absorber include, but are not limited to, tetrahydroxybenzophenone (benzophenone-2), 2-hydroxy-4-methoxybenzophenone (benzophenone-3) (for example, ubinal M40 (trade name); BASF , Escalol 567 (trade name); manufactured by IS Japan, Inc.), benzophenone-4,2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- ( 4-methoxyphenyl) -1,3,5-triazine (eg, Tinosorb S (trade name); manufactured by BASF), drometrizole trisiloxane, and 2,2′-methylenebis [6- (2H-benzotriazole) -2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol] In example, Tinosorb M (trade name), manufactured by BASF), and the like.

When two or more ultraviolet absorbers are used in combination, specifically, a combination of hexyl 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoate and 2-ethylhexyl paramethoxycinnamate, a combination of tert-butyl-4'-methoxydibenzoylmethane, 2-ethylhexyl α-cyano-β-phenylcinnamate (octocrylene) and 2-ethylhexyl paramethoxycinnamate, and 2,4,6-tris [4- Examples include a combination of (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 2-ethylhexyl paramethoxycinnamate and hexyl 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoate.

In the external composition for skin of the present invention, the ultraviolet absorber is, for example, 2-methoxyhexyl paramethoxycinnamate, ferulic acid, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, methoxycinnamic acid Isoamyl, sinoxate, 2-ethylhexyl paradimethylaminobenzoate, para-aminobenzoic acid, ethyl PABA, 3,3′-carbonylbis [4-hydroxy-6-methoxybenzenesulfonic acid] disodium (oxybenzone-9), hydroxy Methoxybenzophenonesulfonic acid (oxybenzone-4), dihydroxybenzophenone (benzophenone-1), α-cyano-β-phenylcinnamic acid 2-ethylhexyl (octocrylene), phenylbenzimidazolesulfonic acid, terephthalylide Didiflufursulfonic acid, drometrizole trisiloxane, dimethicodiethylbenzalmalonate, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxy Phenyl) -1,3,5-triazine, 4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 4-tert-butyl-4′-methoxydibenzoylmethane , Homosalate, TEA salicylate, 2,2′-methylenebis [6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol], menthyl anthranilate, dimethoxybenzylidene Oxoimidazolidine propionate 2-ethylhexyl, 1,1-dicarboxy (2,2′- It is preferably a methyl propyl) -4,4-diphenyl butadiene. In addition, 2-methoxyhexyl paramethoxycinnamate, ferulic acid, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 3,3′-carbonylbis [4-hydroxy-6-methoxybenzenesulfonic acid] Disodium, hydroxymethoxybenzophenonesulfonic acid (benzophenone-1), α-cyano-β-phenylcinnamic acid 2-ethylhexyl (octocrylene), phenylbenzimidazolesulfonic acid, terephthalylidene dicamphulsulfonic acid, dimethicodiethylbenzalmalo Narate, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine, 2,4,6- Tris [4-2-ethylhexyloxycarbonyl) Anilino] -1,3,5-triazine, 4-tert-butyl-4′-methoxydibenzoylmethane, and 2,2′-methylenebis [6- (2H-benzotriazol-2-yl) -4- ( 1,1,3,3-tetramethylbutyl) phenol] is more preferred.

In the composition for external use of the skin of the present invention, as an ultraviolet absorber, one or two or more of the above ultraviolet absorbers are added to microcapsules in order to reduce irritation and odor, or improve the feeling of use and solubility. Raw materials to which formulation modifications such as encapsulating are added can also be used. Specifically, a UV absorber is encapsulated in a shell substantially composed of a polymer component composed of poly (ethylene glycol dimethacrylate), ethylene glycol dimethacrylate / divinylbenzene copolymer, or poly (divinylbenzene), Microcapsules having an average particle size of 0.4 to 10 μm (for example, an ultraviolet absorber-containing capsule described in JP-A-2009-167168), t-butylmethoxydibenzoylmethane encapsulated in sol-gel silica glass, water (For example, Eusolex UV-Pearls OB-S (trade name), Eusolex UV-Pearls OB-S2 (trade name); manufactured by Merck & Co., Inc.) and similarly ethyl hexyl methoxycinnamate in sol-gel silica glass Encapsulate and disperse in water Microcapsules (for example, Eusolex UV-Pearls 2292 (trade name), Eusolex UV-Pearls OMC (trade name); manufactured by Merck & Co., Inc.), and ultraviolet absorbers (octocrylene, diethylaminohydroxybenzoylbenzoic acid, ethylhexyl methoxycinnamate, 2-methoxyhexyl paramethoxycinnamate, t-butyl-methoxydibenzoylmethane, etc.) were encapsulated in silicone-resinized hydrolyzed silk (polysilicone-14) to form microcapsules with an average particle size of 2 μm and dispersed in water. Things (for example, Siloma, ME, Siloma, MEA, Siloma, MEA (S), Siloma, MEA (V), Siloma, MEA (L), Siloma, MFA (S), Si asoma MFA (LS), Silasoma EP (S), Silasoma series (trade name) such as Silasoma REA (S); Seiwa Kasei Co., Ltd.), and others.

In the composition for external use of the skin of the present invention, the content of the ultraviolet absorber may be 0.00001 wt% or more and 30 wt% or less, and may be 0.0001 wt% or more and 20 wt% or less. It may be 0.001% by weight or more and 10% by weight or less, or 0.01% by weight or more and 10% by weight or less.

[Antioxidant]
As the antioxidant (antioxidant component) in the present invention, a known antioxidant can be used as long as the effects of the present invention are not impaired. In the present invention, the antioxidant (antioxidant component, antioxidant component) refers to a drug (component) having a property of inhibiting, reducing, or suppressing oxidation by reactive oxygen species.

As the antioxidant, for example,
(A) Tocopherols and their derivatives or their salts (for example, α-tocopherol, δ-tocopherol, acetic acid-α-tocopherol, tocotrienol), pyrroloquinoline quinone and its derivatives or their salts, ubiquinones and their derivatives or their Vitamin antioxidants, such as salts, retinols and derivatives thereof or salts thereof, pantothenic acid and derivatives or salts thereof, erythorbic acid or salts thereof;
(B) thiotaurine, cysteine, homocysteine, acetylcysteine, methionine, thioglycerol, sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium pyrosulfite, thioredoxin, dithiothreitol, alpha lipoic acid, ergothioneine, glutathione, glutathione peroxidase, Sulfur-containing antioxidants such as glutathione-S-transferase;
(C) phenols such as dibutylhydroxytoluene, dibutylhydroxyanisole, bisethylhexylhydroxydimethoxybenzyl malonate, diethylhexylsyringylidene malonate, gallic acid and its derivatives or their salts, chlorogenic acid and its derivatives or their salts Antioxidants;
(D) components derived from plants (eg, grapes, ginseng, comfrey, etc.) (eg, grape seed extract, grape leaf extract, ginseng extract, comfrey leaf extract, etc.); proanthocyanidins, hesperidins, glucosyl hesperidins, flavonoids ,
And polyphenol-based antioxidants. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the antioxidant is bisethylhexyl hydroxydimethoxybenzyl malonate and derivatives thereof, malonic acid and derivatives thereof, pyrroloquinoline quinone and derivatives thereof, tocopherols and derivatives thereof, thiotaurine and derivatives thereof, Dibutylhydroxytoluene and derivatives thereof, gallic acid or derivatives thereof, chlorogenic acid and derivatives thereof, hesperidin and derivatives thereof, glucosyl hesperidin and derivatives thereof, ergothioneine and derivatives thereof, flavonoids and derivatives thereof, or dibutylhydroxyanisole and derivatives thereof, And when it can take the form of a salt, it is preferable that they are the salt of any one of the said compounds, the salt of any of the said derivatives, etc. Among them, bisethylhexyl hydroxydimethoxybenzyl malonate, pyrroloquinoline quinone and derivatives thereof or salts thereof, tocopherols and derivatives thereof or salts thereof, thiotaurine, dibutylhydroxytoluene, gallic acid and derivatives thereof or salts thereof, chlorogenic acid And its derivatives or their salts, or dibutylhydroxyanisole is more preferred. In addition, bisethylhexyl hydroxydimethoxybenzyl malonate, diethylhexyl syringylidene malonate, pyrroloquinoline quinone and its derivatives or their salts, tocopherol and its derivatives or their salts, thiotaurine, dibutylhydroxytoluene, or gallic acid and its Even more preferred are derivatives or their salts.

In the composition for external use of the skin of the present invention, the content of the antioxidant may be 0.00001 wt% or more and 20 wt% or less, and may be 0.0001 wt% or more and 10 wt% or less. 0.001 wt% or more and 7 wt% or less, 0.05 wt% or more and 5 wt% or less, or 0.03% wt or more and 3 wt% or less. It may be 0.02 wt% or more and 1 wt% or less, or 0.01 wt% or more and 0.5 wt% or less.

[Whitening active ingredient]
As the whitening active ingredient (whitening agent) in the present invention, a known whitening active ingredient can be used as long as the effects of the present invention are not impaired. In the present invention, the whitening active ingredient (whitening agent) is an improvement, suppression / reduction / prevention, prevention of skin pigmentation due to melanin pigment particularly related to dullness and itching of the skin, liver spots, etc. Or it refers to a drug (component) having the property of delaying.

As the whitening active ingredient, for example,
(A) hydroquinone and derivatives thereof or salts thereof (for example, α-arbutin, β-arbutin); kojic acid; ellagic acid; phytic acid; lucinol; ascorbic acid and its derivatives or salts thereof (for example, ascorbic acid phosphate ester) Sodium, magnesium ascorbyl phosphate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), 2-O-ethylascorbic acid, 3-O-ethylascorbic acid, ascorbic acid glucoside, etc.), potassium 4-methoxysalicylate Tyrosinase inhibitors such as salts, tranexamic acid and derivatives thereof or salts thereof;
(B) an endothelin-1 receptor inhibitor such as chamomile ET;
(C) a tyrosinase proteolytic promoter such as free linoleic acid;
(D) a melanin excretion enhancer such as adenosine monophosphate disodium salt;
(E) a melanin transport inhibitor such as niacinamide;
(F) Other plant components having a whitening effect (for example, plant extracts and essential oils);
Can give. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the whitening active ingredient is hydroquinone and derivatives thereof or salts thereof, ascorbic acid and derivatives thereof or salts thereof, tranexamic acid and derivatives thereof or salts thereof, ellagic acid, niacinamide, etc. It is preferable that Among them, hydroquinone, arbutin, sodium ascorbate phosphate, ascorbic acid, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), 3-O-ethylascorbic acid, glucoside ascorbate, More preferred is tranexamic acid.

In the composition for external use of the skin of the present invention, the content of the whitening active ingredient may be 0.00001% by weight to 20% by weight, and is 0.00001% by weight to 10% by weight. 0.001 wt% or more and 7 wt% or less, 0.05 wt% or more and 5 wt% or less, or 0.03% wt or more and 3 wt% or less. It may be 0.02 wt% or more and 1 wt% or less, or 0.01 wt% or more and 0.5 wt% or less.

[Anti-inflammatory ingredients]
As the anti-inflammatory component (anti-inflammatory agent) in the present invention, a known anti-inflammatory component can be used as long as the effects of the present invention are not impaired. In addition, in this invention, an anti-inflammatory component (anti-inflammatory agent) means the chemical | medical agent (component) which has a property which inhibits, reduces, and suppresses inflammation of cells, such as epidermis.

Examples of the anti-inflammatory component include components derived from plants (eg, comfrey leaf extract); allantoin, calamine, glycyrrhizic acid and derivatives thereof or salts thereof (dipotassium glycyrrhizinate, sodium glycyrrhizinate, etc.), glycyrrhetic acid And derivatives thereof or salts thereof (stearyl glycyrrhetinate, 18α-hydroxyglycyrrhetinic acid, etc.), zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, salicylic acid and derivatives thereof. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the anti-inflammatory component is allantoin, glycyrrhizic acid and its derivatives or salts thereof, glycyrrhetinic acid and its derivatives or salts thereof, zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine It is preferably oil, indomethacin, salicylic acid and derivatives thereof, or salts thereof. Of these, allantoin, glycyrrhizic acid, dipotassium glycyrrhizinate, glycyrrhetinic acid, stearyl glycyrrhetinate, zinc oxide, menthol, camphor, indomethacin, and salicylic acid are more preferable.

In the external composition for skin of the present invention, the content of the anti-inflammatory component may be 0.00001 wt% or more and 20 wt% or less, and may be 0.0001 wt% or more and 10 wt% or less. May be 0.001% by weight or more and 5% by weight or less, may be 0.05% by weight or more and 3% by weight or less, and may be 0.03% by weight or more and 1% by weight or less. It may be 0.02 wt% or more and 0.5 wt% or less, or 0.01 wt% or more and 0.1 wt% or less.

[Thickening component]
As the thickening component (thickening agent) in the present invention, a known thickening component can be used as long as the effects of the present invention are not impaired. In the present invention, the thickening component (thickening agent) refers to a drug (component) having the property of increasing the viscosity.

In the composition for external use of the skin of the present invention, the thickening component is an acrylic acid thickener, vinyl thickener, cellulose thickener, mucopolysaccharide thickener, amino acid thickener, seaweed A thickener, a microbial thickener, a polyethylene glycol thickener, a starch thickener, or a plant thickener is preferred.

As the thickening component, for example,
(A) Acrylic acid / alkyl methacrylate copolymer, hydroxyethyl acrylate / acryloyl dimethyl taurate copolymer (especially (hydroxyethyl acrylate / acryloyl dimethyl taurine sodium) copolymer), sodium acrylate / acryloyl dimethyl taurine copolymer Polymer, polyvinyl alcohol, (PEG-240 / decyltetradeceth-20 / HDI) copolymer, (Nacryacrylate / acryloyldimethyltaurine / dimethylacrylamide) crosspolymer, polyacrylic acid or salts thereof molecule;
(B) Vinyl thickeners such as polyvinyl pyrrolidone, polyvinyl alcohol, polyvinyl methyl ether, carboxyvinyl polymer;
(C) Cellulosic thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, stearoxyhydroxypropylmethylcellulose;
(D) mucopolysaccharide thickeners such as hyaluronic acid, hyaluronic acid derivatives and salts thereof, chondroitin sodium sulfate;
(E) amino acid thickeners such as collagen;
(F) Carrageenan, alginates, alginic acid propylene glycol esters, seaweed thickeners such as agar;
(G) Microbial thickeners such as xanthan gum, hydroxypropyl xanthan gum, dextran, sclerotium gum, gellan gum;
(H) polyethylene glycol-based thickeners such as polyethylene glycol, polyethylene glycol distearate, (PEG-240 / decyltetredeces-20 / HDI) copolymer, glyceryl behenate and polyglyceryl octastearate-6;
(I) starch-based thickeners such as hydroxypropyl starch phosphate and corn starch;
(J) Plant thickeners such as guar gum, hydroxypropyl guar gum, locust bean gum, welan gum, karaya gum, gati gum, tamarind gum and pectin;
(K) dextrin fatty acid ester, dimethyl distearyl ammonium hectorite, (acryloyldimethyl taurate ammonium / vinyl pyrrolidone) copolymer, ethylene glycol triisostearate, polyoxyethylene triisostearate (20) methylglucoside, bentonite, macrogol, dibutylethyl Other water-soluble polymers such as hexanoylglutamide, dibutyllauroylglutamide, sodium caseinate;
Etc. These may be used singly or in combination of two or more.

Examples of the acrylic acid / alkyl methacrylate copolymer include (acrylates / alkyl acrylate (C10-30)) crosspolymer, (hydroxyethyl acrylate / acryloyldimethyltaurine sodium) copolymer, acrylamide / ammonium acrylate copolymer, (acrylates). / Beheneth methacrylate-25) cross-polymer sodium, polyacrylate-6, polyacrylate-13, (acrylic acid / acryloyldimethyltaurine / dimethylacrylamide) crosspolymer, (acrylates / stearate itaconate-20) copolymer, (acryloyldimethyltaurine) Ammonium / VP) copolymer, (sodium acrylate / acryloyldimethyltaurine / dimethylacrylamide) crosspolymer Steareth-10 allyl ether-Aku relay retaining clips polymer and the like. In addition, these are commercially available products such as PEMULEN (trademark) TR-1, TR-2 (manufactured by Lubrizol Advanced Materials); Carbopol (trademark) ETD2020, Ultraz20Polymer, Ultrez21 Polymer, and Ultraz10Polymer (LuMold). ) 2001 (manufactured by Akzo Nobel), Aristoflex (trademark) AVC, HMB (manufactured by Clariant Japan) or the like can be used. As the polyvinyl alcohol, for example, commercially available Gohsenol (trademark) EG-05, EG-40 (manufactured by Nippon Synthetic Chemical Industry Co., Ltd.) and the like can be used. Moreover, you may use as a mixture mixed with oil agents, such as squalane, a nonionic surfactant, and water. Specific examples of such a mixture include, for example, SIMULGEL (trademark) FL, NS (manufactured by Sepic), which is a commercial product containing hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer; sodium acrylate / acryloyl Commercial products containing dimethyl taurine copolymer, SIMULGEL (trademark) EG (manufactured by Sepic), SIMULGEL (trademark) EPG (manufactured by Sepic); stealth-10 allyl ether / acrylate copolymer A certain SALCARE ™ SC80 (manufactured by Ciba Specialty Chemicals); a commercially available product, SALCARE ™ SC, containing sodium acrylate, sodium acrylate, sodium methacrylate alkyl methacrylate copolymer 1 (manufactured by Ciba Specialty Chemicals); (NaCl acrylate / acryloyl dimethyl taurine / dimethyl acrylamide) SEPINOV (trademark) P88 (manufactured by Sepic), Adecanol (trademark) GT-700 (Manufactured by Asahi Denka Kogyo Co., Ltd.); and SEPIGEL (trademark) 305 (Seiwa Kasei), which is a commercial product containing polyacrylamide. As said polyacrylic acid amide, commercially available SEPIGEL (trademark) 305 (made by Seiwa Kasei Co., Ltd.) etc. can be used, for example. In addition, as a commercial product containing (PEG-240 / decyltetradeces-20 / HDI) copolymer, Adecanol (trademark) GT-700 (manufactured by Asahi Denka Kogyo Co., Ltd.), and the starch-based thickener, for example, Examples thereof include STRUCTURE (trademark) XL (manufactured by Akzo Nobel), which is a commercial product containing hydroxypropyl starch phosphate.

Among them, acrylic acid-based thickeners include acrylic acid / alkyl methacrylate copolymer, hydroxyethyl acrylate / acryloyldimethyltaurine salt copolymer, sodium acrylate / acryloyldimethyltaurine copolymer, (sodium acrylate) / Acryloyldimethyltaurine / dimethylacrylamide) crosspolymer. Examples of vinyl thickeners include carboxyvinyl polymer, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, dimethyl distearyl ammonium hectorite, (acryloyldimethyltaurine ammonium / vinyl pyrrolidone) copolymer, polyvinyl alcohol, xanthan gum, hydroxypropyl Starch phosphate, polyacrylamide, sodium hyaluronate, hyaluronic acid derivatives or their salts, collagen, agar, xanthan gum, hydroxypropyl starch phosphate, macrogol, dimethyl distearyl ammonium hectorite, (acryloyldimethyl taurate ammonium / vinyl pyrrolidone) A copolymer is preferred.

In the composition for external use of the skin of the present invention, the content of the thickening component may be 0.00001 wt% or more and 20 wt% or less, and may be 0.0001 wt% or more and 10 wt% or less. May be 0.001% by weight or more and 5% by weight or less, may be 0.05% by weight or more and 3% by weight or less, and may be 0.03% by weight or more and 1% by weight or less. It may be 0.02 wt% or more and 0.5 wt% or less, or 0.01 wt% or more and 0.1 wt% or less.

[Other bases or carriers]
The external composition for skin of the present invention can contain a known base or carrier used for cosmetics and quasi-drugs as long as the effects of the present invention are not impaired. A base or a carrier can be used singly or in combination of two or more.

Bases or carriers include paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbons (such as plastibase), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin oligomer, light liquid paraffin, etc. Hydrocarbons; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid; glyceryl tri-2-ethylhexanoate (trioctanoin), tri (caprylic acid / capric acid) glyceryl Tri-fatty acid glycerides; higher alcohols such as cetanol, stearyl alcohol, behenyl alcohol; methyl polysiloxanes, highly polymerized methyl polysiloxanes, dimethyl siloxane methyl (polyoxyethylene) siloxane (Polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene / methylpolysiloxane copolymer, Poly (oxyethylene / oxypropylene) / methylpolysiloxane copolymer, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, crosslinking Type methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether modified silicone, crosslinked alkyl polyether modified silicone, crosslinked alkyl modified silicone, decamethylcyclope Such as intersiloxane, ethyltrisiloxane, methyltrimethicone, methylsiloxane network polymer, polyoxyethylene-methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyldimethicone, dimethylpolysiloxane Silicone oils; such as ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol diacetate Glycol acetate; triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, 2,2,4-trimethyl-1,3-pentanediol Glycol esters such as isobutyrate; such as ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1,3-butylene glycol diacrylate Glycol acrylates; glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2 ′-[1,4-phenylenedioxy] diethanol; ethylcellulose , Cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose; polyvinylpyrrolidone; carrageenan; Polybutylene glycol; Dioxane; Butylene glycol adipate polyester; Esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythrite tetra-2-ethylhexanoate; dextrin Polysaccharides such as maltodextrin; lower alcohols such as ethanol and isopropanol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol Monobutyl ether, pro Examples thereof include glycol ethers such as pyrene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether and dipropylene glycol monopropyl ether; water-based bases such as water.

Among them, hydrocarbons (especially α-olefin oligomers, squalane, light liquid paraffin, liquid paraffin), trifatty acid glycerides (especially glyceryl tri-2-ethylhexanoate, tri (caprylic acid / capric acid) glyceryl), higher alcohols (Especially cetanol, stearyl alcohol, behenyl alcohol), silicone oil (especially methylpolysiloxane, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methylpolysiloxane, decamethylcyclopentasiloxane, ethyltrisiloxane, methyltrimethicone , Methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyldi Chicone, dimethylpolysiloxane), esters (especially isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate), polysaccharides (especially dextrin, maltodextrin), glycol ethers (especially diethylene glycol monoethyl ether), water Is preferred.

[Additive]
To the skin external composition of the present invention, known additives that are added to cosmetics and quasi drugs, for example, surfactants, preservatives, pH adjusters, chelating agents, as long as the effects of the present invention are not impaired , Stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, pearlescent agents, and the like can be added. An additive can be used individually by 1 type or in combination of 2 or more types.

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; glyceryl fatty acids such as glyceryl monostearate and glyceryl monostearate; polyglyceryl fatty acids such as polyglyceryl monostearate, polyglyceryl monoisostearate and polyglyceryl diisostearate; propylene glycol monostearate Propylene glycol fatty acid esters such as: polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hardened Cured castor oil derivatives such as castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20) , Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene monooxylate (20) sorbitan (polysorbate 80), polyoxyethylene (20) sorbitan isostearate Polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether; Examples include amines such as ruamine; silicone surfactants such as polyoxyethylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. .

Among them, glycerin fatty acids (particularly glyceryl monostearate), polyglycerin fatty acids (particularly polyglyceryl monostearate), hydrogenated castor oil derivatives (particularly polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxy Ethylene hydrogenated castor oil 60 (HCO-60)), polyoxyethylene sorbitan fatty acid esters (particularly polyoxyethylene (20) sorbitan isostearate, polyoxyethylene (20) sorbitan monostearate (polysorbate 60)), polyoxy Alkylene alkyl ether (especially polyoxyethylene cetyl ether), silicone surfactant (especially polyoxyethylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, P G-9 polydimethylsiloxyethyl dimethicone) is preferred.

Preservatives and preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, paraoxybenzoic acid Examples thereof include benzyl, methyl paraoxybenzoate, and phenoxyethanol. Of these, methyl paraoxybenzoate, propyl paraoxybenzoate, and phenoxyethanol are preferable.

Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, sodium succinate, Oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, hydroxide) And potassium (sodium hydroxide, calcium hydroxide, magnesium hydroxide, etc.), organic bases (monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.). Of these, succinic acid, sodium succinate, citric acid, sodium citrate, triethanolamine, potassium hydroxide, and sodium hydroxide are preferable.

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, metalin Acids can be raised. Of these, sodium edetate is preferred.

Examples of stabilizers 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 the colorant include inorganic pigments and natural pigments.

Examples of the pearl luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate. Of these, ethylene glycol distearate is preferred.

[Other active ingredients]
In the present invention, the composition for external use of skin includes an anti-aging component, a keratin softening component, a cell activation component, vitamins, a blood circulation promoting component, a moisturizing component, DNA damage prevention and , / Or other active ingredients that can be added to cosmetics and quasi-drugs, such as components having a restorative action, ultraviolet scattering components, cleaning components, antibacterial components, and astringent components. Other active ingredients can be used singly or in combination of two or more.

Anti-wrinkle and anti-aging components include hydrolyzed soy protein, retinoids (retinol and its derivatives, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl -L-serine, mevalonolactone and the like can be mentioned. Of these, artemia extract, hydrolyzed soy protein, retinol, retinol acetate, and retinol palmitate are preferred.

Examples of the keratin soft component include lanolin, urea, α-hydroxy acid (phytic acid, lactic acid, lactate, glycolic acid, salicylic acid, malic acid, etc.), citric acid, and the like. Of these, lactic acid, sodium lactate, glycolic acid, salicylic acid, and phytic acid are preferable.

Cell activation components include components derived from plants (eg, bilberry); amino acids such as γ-aminobutyric acid and ε-aminoproic acid; vitamins such as retinol and its derivatives, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids And α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponins, allantoins, and photosensitizer 301. Of these, bilberry leaf extract, retinol, retinol acetate, and retinol palmitate are preferred.

Vitamins include retinol, retinol acetate, retinol palmitate, etc., retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocopheryl retinoate Vitamins such as β-tocopheryl retinoate; provitamins A such as β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthin, echinone; δ-tocopherol, α- Vitamin Es such as tocopherol, β-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, δ-tocopherol and tocopherol nicotinate; riboflavin, flavin mononucleotide Vitamin B2 such as flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5′-phosphate, riboflavin tetranicotinate; nicotinic acids such as methyl nicotinate, nicotinic acid, nicotinamide; stearin Ascorbyl acid, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbine Vitamin C such as acid glucoside, 2-O-ethylascorbic acid, 3-O-ethylascorbic acid; methyl hesperidin, Vitamin Ds such as ergocalciferol and cholecalciferol; vitamin Ks such as phylloquinone and farnoquinone; dibenzoyl 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, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate Vitamin B1 such as acid ester monophosphate; Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, pyridoxamine hydrochloride, cyano Vitamin B12 such as balamine, hydroxocobalamin, deoxyadenosylcobalamin; folic acid such as folic acid, pteroylglutamic acid; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethein, D-panthetin, coenzyme A, pantothenic acids such as pantothenyl ethyl ether; biotins such as biotin and biocytin; and vitamin-like agents such as carnitine, ferulic acid, α-lipoic acid, orotic acid, and γ-oryzanol.

Among them, vitamin A such as retinol, retinol acetate and retinol palmitate; ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), 2- Vitamin Cs such as O-ethylascorbic acid and 3-O-ethylascorbic acid; vitamin Es such as δ-tocopherol and tocopherol nicotinate; and nicotinic acids such as nicotinamide are preferred.

Examples of the blood circulation promoting component include plants (for example, ginseng, ashitaba, arnica, ginkgo, fennel, enmelio, dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, prunus, nematode, Assembly, thyme, clove, chimney, spruce, spruce, spruce, carrot, garlic, butcher bloom, grape, button, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpy, touki, spruce, peach, apricot, walnut Ingredients derived from corn); tocopherol nicotinate, glucosyl hesperidin, hesperidin. Of these, ginseng extract, tocopherol nicotinate, glucosyl hesperidin, and hesperidin are preferable.

Moisturizing ingredients include ingredients derived from plants (eg, Tigaya); amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, theanine and derivatives thereof; collagen, gelatin, elastin Such proteins and peptides, hydrolysates thereof; polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, diglycerin; sugar alcohols such as sorbitol; lecithin, hydrogenated lecithin Phospholipids such as: hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, heparin, chondroitin mucopolysaccharides; lactic acid, pyrrolidone carbo NMF-derived components such as sodium acid and urea; polyglutamic acid; macromolecules having phospholipid polar groups such as MPC polymers (for example, LIPIDURE ™); polyoxypropylene methyl glucoside; PPG-10 methyl glucose (for example, Macbiobride MG (trademark) series (manufactured by NOF Corporation, etc.), PEG / PPG / polybutylene glycol-8 / 5/3 glycerol (for example, Wilbride (trademark) S-753 (manufactured by NOF CORPORATION) ); Trimethylglycine (betaine); hydroxyethyl urea; acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer; sorbitol and the like. Among them, chigaya root extract, hydrolyzed collagen, hydrolyzed elastin, MPC polymer glycerin, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, diglycerin, polyoxypropylene methyl glucoside, trimethylglycine (betaine), hydroxyethyl Urea, acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer, hydrogenated lecithin, hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate and sorbitol are preferred.

Components having a preventive and / or repairing action on DNA damage include components derived from animals (eg, Artemia); components derived from plants (eg, cat's claw); DNA, DNA salts, RNA, RNA salts, etc. Of the nucleic acid component. Of these, artemia extract and DNA-Na are preferable.

Ultraviolet scattering components 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, and those inorganic compounds Coated with hydrous silicic acid, aluminum hydroxide, coated with inorganic powder such as mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene, nylon, silicon oil and The thing processed with fatty acid aluminum salt etc. can be mention | raise | lifted. Of these, inorganic compounds such as zinc oxide, titanium oxide and iron oxide, and those inorganic compounds coated with inorganic powder such as aluminum hydroxide, hydrous silicic acid, mica and talc, and silicon oil are preferable.

As washing components, polyoxyalkylene alkyl (or alkenyl) ether sulfate, alkyl (or alkenyl) sulfate, higher fatty acid salt, ether carboxylate, amide ether carboxylate, alkyl phosphate ester salt, N-acyl amino acid Anionic surfactants such as salts, polyoxyalkylene fatty acid amide ether sulfates, acylated isethionates, acylated taurates; amine oxides, glycerin fatty acid esters, sorbitan fatty acid esters, alkyl saccharides, polyoxyalkylene alkyl ethers, fatty acid alkanolamides A nonionic surfactant such as polyoxyalkylene hydrogenated castor oil; a mono- or di-long alkyl having a linear or branched long-chain alkyl group to which an alkylene oxide may be added Cationic surfactants such as quaternary ammonium salts; carboxymethyl betaine, sulfobetaine, imidazolinium betaine, may be mentioned amphoteric surfactants such as betaines.

Of these, anionic surfactants, nonionic surfactants, and amphoteric surfactants are preferred. Anionic surfactants include higher fatty acid salts (particularly salts of higher fatty acids such as palmitic acid, lauric acid, myristic acid, stearic acid), N-acyl amino acid salts (particularly sodium N-lauroyl aspartate, potassium hydroxide / N-coconut oil fatty acid potassium acylglutamate, coconut oil fatty acid acylglycine sodium, myristoyl glutamic acid) is preferred. Among the nonionic surfactants, fatty acid alkanolamides (especially coconut oil fatty acid diethanolamide, coconut oil fatty acid monoethanolamide) and amine oxides (especially coconut oil alkyldimethylamine oxide, lauryldimethylamine oxide) are preferable. Amphoteric surfactants include imidazolinium betaines (especially 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolium betaine, N-coconut oil fatty acid acyl-N-carboxymethoxyethyl-N-carboxymethylethylenediamine disodium ) Is preferred.

Antibacterial components include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101 Photosensitive element 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, and the like. Among them, benzalkonium chloride, benzethonium chloride, gluconic acid and derivatives thereof, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiamino hydrochloride Glycine is preferred, and benzalkonium chloride, gluconic acid and its derivatives, benzethonium chloride, and isopropylmethylphenol are more preferred.

Convergent components include metal salts such as alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, and aluminum potassium sulfate; organic acids such as tannic acid, citric acid, lactic acid, and succinic acid. Of these, alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, potassium aluminum sulfate, and tannic acid are preferable.

[Formulation]
In addition, the external composition for skin in the present invention can be prepared by mixing and stirring each component according to a conventional method, for example.

In the composition for external use in skin according to the present invention, the form of the drug is not particularly limited, and a form known as a form of cosmetics or quasi drugs can be taken. As such known forms, for example, liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, powders, poultices, nonwoven fabrics and the like are impregnated with chemicals. And a stick agent such as a lipstick. Of these, liquids, suspensions, emulsions, creams, ointments, gels, and lotions are preferred, and liquids, emulsions, creams, gels, and lotions are more preferred in terms of good usability. In particular, the benzylidene azolidine derivative or salt thereof is excellent in solubility in the base (particularly hydrophilic) and easy to formulate (water-soluble agent). Formulation forms of emulsions, aqueous gels and aqueous lotions are preferred. Further, depending on the formulation, an oil-in-water type (O / W), a water-in-oil type (W / O), and the like can be appropriately selected according to the purpose of use and desired feeling of use.

In addition, the specific use of the cosmetic composition is not particularly limited, and basic cosmetics such as lotion, milky lotion, cream, cosmetic liquid, sunscreen cosmetics, packs, hand creams, body lotions, body creams; Cosmetics for cleaning such as makeup removers, body shampoos, shampoos and rinses; makeup cosmetics such as foundations, concealers, makeup bases, lip balms, lipsticks and teak colors; bathing agents and the like.

In the case where the composition for external use of the skin of the present invention takes any of the above forms, the benzylidene azolidine derivative or a salt thereof and a specific drug (ultraviolet absorber, antioxidant, whitening active ingredient, anti-inflammatory ingredient, and The total content of the thickening component) may be 0.00001 wt% or more and 50 wt% or less, and may be 0.0001 wt% or more and 20 wt% or less, and 0.001 wt% % To 10% by weight, 0.005% to 5% by weight, 0.01% to 3% by weight, 0.05% to 0.05% by weight It may be 1% by weight or less.

Hereinafter, examples and the like specifically showing the configuration and effects of the present invention will be described. In addition, the evaluation item in an Example etc. measured as follows.

<Measurement of ¹ H-NMR spectrum>
^{The 1} H-NMR spectrum was measured using a nuclear magnetic resonance apparatus (JNM-ECP500, manufactured by JEOL Ltd.). More specifically, the ¹ H-NMR spectrum was measured using DMSO-d ₆ as a solvent and tetramethylsilane as an internal standard.

<Measurement of UV spectrum>
The measurement of the UV spectrum was performed using a spectrophotometer (manufactured by Shimadzu Corporation, UV-4250). More specifically, the UV spectrum was measured using a quartz cell with ethanol as a solvent, a sample solution concentration of 5 ppm, and an optical path length of 1 cm. The absorbance was calculated according to Lambert-Beer's law, where Io was the transmitted light intensity of the empty cell and I was the transmitted light intensity of the sample cell, with absorbance = −log ₁₀ (I / I ₀ ). Further, the wavelength at which the absorbance in the obtained UV spectrum becomes maximum was defined as λmax (nm).

<Hydrophilicity evaluation>
The obtained compound (1) was dissolved in the test solvent shown below, the properties were confirmed, and the solubility (g / 100 g test solvent) at 25 ° C. with respect to 100 g of the test solvent was measured.
Test solvent: Mixed solvent containing dipropylene glycol, ethanol, and purified water in amounts of 10% by mass, 10% by mass, and 80% by mass, respectively (however, the total of dipropylene glycol, ethanol, and purified water) (The amount is 100% by mass.)

In addition, hydrophilicity evaluation was performed as follows by the difference in solubility.
・ In the case of 1.0 or more (g / 100 g test solvent): The hydrophilicity is particularly high. ・ From 0.2 to less than 1.0 (g / 100 g test solvent): The hydrophilicity is high. If less than 0.2 (g / 100 g test solvent): poor hydrophilicity. If less than 0.1 (g / 100 g test solvent), if there is a solid suspension: not hydrophilic

[Example 1]
(Synthesis of Compound (1))
In a 300 mL eggplant type flask, 16.4 g (132 mmol) of 2- (2-chloroethoxy) ethanol, 33.2 g (240 mmol) of potassium carbonate, and 150 mL of acetonitrile were added to 14.7 g (120 mmol) of 4-hydroxybenzaldehyde. Heated at 105 ° C. with stirring for 14 hours. Further, 1.49 g (12.0 mmol) of 2- (2-chloroethoxy) ethanol was added and heated at 105 ° C. with stirring for 30 hours. After the reaction mixture cooled to room temperature, the solid was removed by celite filtration. The solvent was distilled off under reduced pressure to obtain 34.6 g of a yellow viscous substance mixed with a white solid.

To this, 80 mL of water was added, transferred to a separately prepared 200 mL eggplant-shaped flask, 15.6 g (156 mmol) of hydantoin and 14.4 g of 28% aqueous ammonia were added, and the mixture was heated at 90 ° C. with stirring for 12 hours. After the reaction mixture had cooled to room temperature, the precipitated crystals were collected by filtration. Thereafter, the crystals were washed twice with water and twice with ethanol. After drying, 29.6 g of 5- [4- [2- (2-hydroxyethoxy) ethoxy] benzylidene] hydantoin was obtained.

Subsequently, 17.5 g (60.0 mmol) of the obtained product was added to 7.47 g (60 mmol) of 2- (2-chloroethoxy) ethanol, 20.0 g (145 mmol) of potassium carbonate in a 200 mL eggplant type flask, N, N-dimethylformamide (80 mL) was added, and the mixture was heated at 110 ° C. with stirring for 3 hours. After the reaction mixture cooled to room temperature, the solid was removed by celite filtration. The solvent was distilled off under reduced pressure to obtain 30.5 g of a yellow viscous substance mixed with a white solid. This was purified by silica gel column chromatography (developing solvent; isopropanol: toluene = 1: 3) to obtain 9.21 g of yellow crystals. This was treated with activated carbon with ethanol and recrystallized to obtain 6.56 g of the following compound (1) (yield: 25%).

5- [4- [2- (2-hydroxyethoxy) ethoxy] benzylidene] -3- [2- (2-hydroxyethoxy) ethyl] hydantoin (compound (1))

(Spectral data of compound (1), etc.)
UV spectrum: [lambda] max; 335 nm, absorbance; 0.43 (ethanol).
¹ H-NMR spectrum: δ [ppm, DMSO-d ₆ ] = 3.41-3.46 (m, 4H), 3.48-3.53 (m, 4H), 3.60 (m, 2H) , 3.64 (m, 2H), 3.75 (t, 2H), 4.15 (t, 2H), 4.61 (t, 1H), 4.67 (t, 1H), 6.52 ( s, 1H), 6.99 (d, 2H), 7.62 (d, 2H), 10.71 (s, 1H).
Solubility: 2.0 (g / 100 g test solvent), especially hydrophilic.

[Examples 2 to 8, Comparative Example 1]
(Test Example 1: Light stabilization effect by antioxidant)
A test solution was prepared based on the formulation shown in Table 1 below, and 2 mL / cm ² was applied on a polymethyl methacrylate plate. Among them, a plate (irradiated sample) for irradiating light was irradiated with light at an irradiance of 500 W / m ² for 10 minutes using a sun tester (SUNTEST XLS +; manufactured by Toyo Seiki Seisakusho) as a light irradiation device. Meanwhile, the plate not irradiated with light (unirradiated sample) was stored in the dark at the same temperature (35 ± 2 ° C.) for the same time. Thereafter, the compound (1) was extracted by immersing the unirradiated sample and the irradiated sample in 50 mL of ethanol and treating them with ultrasound for 15 minutes.

The obtained solution was analyzed with an ultraviolet-visible spectrophotometer (UV-2450; manufactured by Shimadzu Corporation), and the residual ratio of compound (1) was calculated. More specifically, the values obtained by dividing the area under the absorbance curve (AUC) at 320-400 nm of the irradiated sample by the AUC of the unirradiated sample were obtained by Equation 1, respectively. The calculation formula is as follows.
[Formula 1]
[(AUC of irradiated sample) / (AUC of unirradiated sample)] × 100 (%)

Moreover, the stability improvement rate of the compound (1) was calculated according to the formula 2 using the compound (1) residual rate calculated by the formula 1 as a relative value to the value of the comparative example 1.
[Formula 2]
[(Compound (1) remaining rate of each example) / (Comparative example compound (1) remaining rate]] × 100) -100 (%)

The obtained results are shown in Table 1.

As can be seen from Table 1, it was confirmed that the light stability of the compound (1) was improved by using the antioxidant together.

[Examples 9 to 12]
(Test Example 2: Light stabilization effect by ultraviolet absorber)
A test solution was prepared based on the formulation shown in Table 2 below, and the residual ratio of compound (1) was determined in the same manner as in Test Example 1. Also, since the ultraviolet absorber itself has UV absorption at 320-400 nm, a sample not containing Compound (1) is separately prepared, and similarly, AUC is obtained and subtracted from them to obtain the ultraviolet absorber. Correction was made according to Equation 3 so that the increase in its own AUC did not directly affect the results.
[Formula 3]
[(AUC of irradiated sample-AUC of compound (1) unblended irradiated sample) / (AUC of unirradiated sample-AUC of compound (1) unblended unirradiated sample)] × 100 (%)

Further, the stability improvement rate of the compound (1) was calculated according to the formula 2 by using the residual ratio of the compound (1) calculated by the formula 3 as a relative value with respect to the value of the comparative example 1.

The obtained results are shown in Table 2.

As can be seen from Table 2 above, it was confirmed that the light stability of the compound (1) was improved by using the ultraviolet absorber in combination.
(Reagent used)
・ 3,3′-carbonylbis [4-hydroxy-6-methoxybenzenesulfonic acid] disodium (Ubinal DS49)
・ Hydroxymethoxybenzophenonesulfonic acid (Ubinal MS40)
-Octocrylene (Yubinar 539N)

[Examples 13 to 16, Comparative Example 2]
(Test Example 3: Light stabilization effect by thickener)
A sample blended based on the blending in Table 3 below was prepared so as to have a pH of about 6 to 7, filled in a glass vial (screw cap), incubated at 25 ° C., and used as a measurement sample before UV irradiation. The sample was irradiated with light at an irradiance of 350 W / m ² for 1 hour using a sun tester (SUNTEST XLS +; manufactured by Toyo Seiki Seisakusho). The sample was incubated at 25 ° C., and then 2 mL / cm ² was applied onto a polymethyl methacrylate plate. Next, the absorbance of the UV-irradiated sample was measured using a spectrum meter (V-650 SPECTROPHOMETER, manufactured by JASCO, attached to ISV722), and the rate of change in absorbance at 340 nm, which is the absorption maximum of compound (1), was determined by Equation 4.
[Formula 4]
Compound (1) residual ratio (%) = [(absorbance of sample after irradiation) / (absorbance of sample before irradiation)] × 100

Further, the stability improvement rate of the compound (1) was calculated according to the above formula 3 as a relative value with respect to the value of Comparative Example 2.

The obtained results are shown in Table 3.

As can be seen from Table 3 above, it was confirmed that the light stability of the compound (1) was improved by using the thickener together.

[Examples 17 to 19, Comparative Example 3]
(Test Example 4: Light stabilization effect by whitening agent and anti-inflammatory agent)
A sample blended based on the blending shown in Table 4 below was prepared, filled in a glass vial (screw cap), made constant at 25 ° C., and used as a measurement sample before UV irradiation. The sample was irradiated with light at an irradiance of 500 W / m ² for 20 minutes using a sun tester (SUNTEST XLS +; manufactured by Toyo Seiki Seisakusho). Thereafter, the sample diluted 100 times with ethanol is transferred to a 24 well plate by 1 mL, and the absorbance at 340 nm, which is the maximum absorption of the compound (1), is measured with a microplate reader, and the rate of change of the compound (1) and The stability improvement rate was determined in the same manner as in Test Example 3.

As can be seen from Table 4 above, it was confirmed that the light stability of the compound (1) was improved by using the whitening agent and the anti-inflammatory agent in combination.

[Examples 20 to 22, Comparative Examples 4 to 6]
(Test Example 5: Effect of enhancing ultraviolet absorbing ability by ultraviolet absorber)
A sample blended based on the blending in Table 5 below was prepared to have a pH of about 6 to 7, filled in a glass vial (screw cap), and kept at 25 ° C., and used as a measurement sample. Each of the above samples was applied at ² mL / cm ² on a polymethyl methacrylate plate. Next, the absorbance of each of the above samples was measured using a spectrum meter (V-650 SPECTROTOPOMETER manufactured by JASCO, attached to ISV722).

(Reagent used)
Paramethoxy cinnamate 2-ethylhexyl: ubinal MC80
2- [4- (Diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester: ubinal A plus As can be seen from FIGS. 1 to 3, the UV absorption ability mainly at the absorption maximum is obtained by using the above UV absorber together. Has been confirmed to improve.

[Examples 23 to 35, Comparative Examples 7 to 18]
(Test Example 6: Evaluation of UV absorbing ability by UV absorber)
Samples formulated based on the formulations shown in Tables 6 to 10 below were prepared so as to have a pH of about 6 to 7, 10 g each was filled into a 10 mL glass vial (screw cap), measured at 25 ° C., and before UV irradiation. A sample was used. Each sample was applied at 2 mL / cm 2 on a polymethyl methacrylate plate. Next, the spectrum change (FIGS. 4 to 8) in each formulation was observed using a spectrum meter (V-650 SPECTROTOPOMETER manufactured by JASCO, attached to ISV722).

As can be seen from Tables 6 to 10 and FIGS. 4 to 8, even when used in combination with the ultraviolet absorber (UV-B group absorber) as an example of the present application, the UV absorption ability is not adversely affected. confirmed. In addition, the value was not particularly affected in either the glass cell or the quartz cell.

[Examples 36 to 39]
(Test Example 7: Light stabilization effect by whitening agent and anti-inflammatory agent)
Samples formulated based on the formulation shown in Table 11 below are prepared so that the pH is about 6 to 7, 10 g each is filled into a 10 mL glass vial (screw cap), and the sample is measured at 25 ° C. and then before UV irradiation. It was. The sample was irradiated with light at an irradiance of 350 W / m ² for 1 hour using a sun tester (SUNTEST XLS +; manufactured by Toyo Seiki Seisakusho). The sample was incubated at 25 ° C., and then 2 mL / cm ² was applied onto a polymethyl methacrylate plate. Next, the absorbance of the UV-irradiated sample was measured using a spectrometer (V-650 SPECTROPHOMETER, manufactured by JASCO, attached to ISV722), and the change in the spectrum of Compound (I) before and after UV irradiation was observed.

As can be seen from Table 11, it was confirmed that the light stability of the compound (1) was improved by using the whitening agent and the anti-inflammatory agent in combination.

Hereinafter, formulation examples in the present invention will be described. The pH of each formulation example was adjusted to 4-8.

In the table, the UV-encapsulating capsules include 2-ethylhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, and t-butylmethoxydibenzoylmethane as UV absorbers. Alternatively, octocrylene is encapsulated in microcapsules made from styrene and its derivatives or (meth) acrylic acid and its derivatives.

Claims

A benzylidene azolidine derivative represented by the general formula (I) or a salt thereof,

(In the structural formula (I), n is an integer of 1 to 5, A 1 is O, S, or NA 4 , and A 2 , A 3, and A 4 are each independently hydrogen An atom, an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group, a functional group (1) represented by the following structural formula (1), a functional group (2) represented by the following structural formula (2), Or a functional group (3) represented by the following structural formula (3) (provided that at least one of A 2 , A 3 and A 4 contains one or more hydroxyl groups), and n is 2 In the case of an integer of ˜5, a plurality of A 3 —O— may be the same or different.)

(In Structural Formula (1), X 1 is an alkylene group having 2 to 4 carbon atoms, R 1 is a hydroxyalkyl group having 2 to 4 carbon atoms, and m is an integer of 1 to 4. When m is an integer of 2 to 4, a plurality of X 1 may be the same or different.)

(In Structural Formula (2), X 2 is an alkylene group having 2 to 4 carbon atoms, R 2 is a hydroxyalkyl group having 2 to 4 carbon atoms, p is 1 or 2, and q is 0 And when q is an integer of 2 to 4, a plurality of X 2 may be the same or different.)

(In Structural Formula (3), X 3a and X 3b are each independently an alkylene group having 2 to 4 carbon atoms, and R 3a and R 3b are each independently a hydroxyalkyl having 2 to 4 carbon atoms. And r is 1 or 2, and s and t are each independently an integer of 0 to 4. When s is an integer of 2 to 4, a plurality of X 3a are the same or different And when t is an integer of 2 to 4, a plurality of X 3b may be the same or different.)
And
An external composition for skin comprising at least one selected from the group consisting of an ultraviolet absorber, an antioxidant, a whitening active ingredient, an anti-inflammatory ingredient, and a thickening ingredient.
In the structural formula (I), at least one of A 2 , A 3 and A 4 is the functional group (1), the functional group (2), or the functional group (3). The external composition for skin according to claim 1, characterized in that it is characterized in that
In the structural formula (I), A 2 and / or A 3 is a hydrogen atom, a C 1-8 alkyl group substituted with a hydroxyl group, the functional group (1), the functional group (2), Or the said functional group (3), The composition for external use of the skin of Claim 1 or 2 characterized by the above-mentioned.
The external composition for skin according to any one of claims 1 to 3, wherein the structural formula (I) is a benzylidene azolidine derivative represented by the following structural formula (II) or a salt thereof.

(In Structural Formula (II), n ′ is an integer of 0 to 4, and when n ′ is an integer of 1 to 4, a plurality of A 3 —O— may be the same or different. )
The external composition for skin according to any one of claims 1 to 4, wherein the structural formula (I) is a benzylidenehydantoin derivative represented by the following structural formula (III) or a salt thereof.
The ultraviolet absorber is cinnamic acid derivative, benzoic acid derivative, salicylic acid derivative, benzophenone derivative, benzylidene camphor derivative, triazine derivative, phenylbenzimidazole derivative, phenylbenzotriazole derivative, anthranil derivative, imidazolidine derivative, benzalmalonate derivative, The external composition for skin according to any one of claims 1 to 5, wherein the composition is one or more selected from the group consisting of a dibenzoylmethane derivative and a 4,4-diarylbutadiene derivative.
The antioxidant according to any one of claims 1 to 5, wherein the antioxidant is one or more selected from the group consisting of vitamin-based antioxidants, sulfur-containing antioxidants, phenol-based antioxidants, and polyphenol-based antioxidants. The external composition for skin according to any one of the above.
The whitening active ingredient is at least one selected from the group consisting of a tyrosinase inhibitor, an endothelin-1 receptor inhibitor, a tyrosinase proteolysis promoter, a melanin excretion promoter, and a melanin transport inhibitor. The composition for external use on the skin according to any one of 1 to 5.
The anti-inflammatory component is allantoin, calamine, glycyrrhizic acid and derivatives thereof or salts thereof, glycyrrhetinic acid and derivatives or salts thereof, zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, and salicylic acid. The external composition for skin according to any one of claims 1 to 5, which is one or more selected from the group consisting of:
The thickening component is an acrylic acid thickener, vinyl thickener, cellulose thickener, mucopolysaccharide thickener, amino acid thickener, seaweed thickener, microbial thickener. The external composition for skin according to any one of claims 1 to 5, wherein the composition is one or more selected from the group consisting of: a polyethylene glycol thickener, a starch thickener, and a plant thickener.