WO2015046390A1 - Composition for external application to skin containing novel benzylidene azolidine derivative or salt thereof - Google Patents

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 dissolution stability, 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 organic acids, hydroxyalkyl ureas, polyhydric alcohols, alkyl ethers thereof, and hydroxyalkyl amines. (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 includes a novel benzylidene azolidine derivative or a salt thereof, and at least one selected from an organic acid, a hydroxyalkyl urea, a polyhydric alcohol or an alkyl ether thereof, and a hydroxyalkylamine. The present invention relates to an external composition for skin.

The present invention also relates to an external composition for skin containing a benzylidene azolidine derivative or a salt thereof. More specifically, the present invention relates to an external composition for skin comprising a benzylidene azolidine derivative or a salt thereof, a glycol compound, and a hydroxyalkylurea.

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.

Near-ultraviolet rays generally called “ultraviolet rays (UV)” are roughly classified into UVA (wavelengths 315 to 400 nm), UVB (wavelengths 280 to 315 nm), and UVC (wavelengths 200 to 280 nm) based on the wavelength. Is done. 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 addition, when used for applications such as cosmetics, solubility in the base is required. In particular, from the viewpoint of usability, aesthetics, etc., characteristics such as no UV-absorbing substance being deposited or not being deposited are also required.

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

In light of such circumstances, the present invention provides the dissolution stability of a benzylidene azolidine derivative and a salt thereof, which is a novel hydrophilic hydrophilic compound having a UV absorbing action (particularly UVA absorbing action) and safe for the skin. An object is to provide an improved skin external composition.

In addition, in light of such circumstances, the present invention is a dissolution stability of a benzylidene azolidine derivative, which is a neutral compound having a UV-absorbing action (particularly a UVA-absorbing action) and being hydrophilic and safe for the skin, and salts thereof. An object of the present invention is to provide a composition for external use on the skin with improved skin. In particular, an object of the present invention is to provide an external composition for skin having improved solubility in a hydrophilic solvent, solubility after low-temperature storage, and transparency.

(First embodiment of the present invention)
As a result of intensive studies to solve the above problems, the present inventors have succeeded in creating a novel benzylidene azolidine derivative or a salt thereof shown below, and the compound, an organic acid, a hydroxyalkylurea, a polyhydric alcohol or a salt thereof. It has been found that the object can be achieved by a composition for external use containing an alkyl ether and at least one selected from hydroxyalkylamines, and the present invention has been completed.

　　（構造式（Ｉ）中、ｎは１～５の整数であり、Ａ^１は、Ｏ、Ｓ、またはＮ－Ａ^４であり、Ａ^２、Ａ^３およびＡ^４は、それぞれ独立に、水素原子、ヒドロキシル基で置換されていてもよい炭素数１～８のアルキル基、下記構造式（１）で表わされる官能基（１）、下記構造式（２）で表わされる官能基（２）、または下記構造式（３）で表わされる官能基（３）である（ただし、少なくともＡ^２、Ａ^３およびＡ^４のいずれかに１つ以上のヒドロキシル基を含むものとする）。また、ｎが２～５の整数である場合、複数存在するＡ^３－Ｏ－は、同一でも異なっていてもよい。）

　　（構造式（１）中、Ｘ^１は、炭素数２～４のアルキレン基であり、Ｒ^１は、炭素数２～４のヒドロキシアルキル基であり、ｍは、１～４の整数である。ｍが２～４の整数である場合、複数存在するＸ^１は、同一でも異なっていてもよい。）

　　（構造式（２）中、Ｘ^２は、炭素数２～４のアルキレン基であり、Ｒ^２は炭素数２～４のヒドロキシアルキル基であり、ｐは１または２であり、ｑは、０～４の整数であり、ｑが２～４の整数である場合、複数存在するＸ^２は、同一でも異なっていてもよい。）

　　（構造式（３）中、Ｘ^３ａおよびＸ^３ｂは、それぞれ独立に、炭素数２～４のアルキレン基であり、Ｒ^３ａおよびＲ^３ｂは、それぞれ独立に炭素数２～４のヒドロキシアルキル基であり、ｒは１または２であり、ｓおよびｔは、それぞれ独立に０～４の整数である。ｓが２～４の整数である場合、複数存在するＸ^３ａは、同一でも異なっていてもよいし、ｔが２～４の整数である場合、複数存在するＸ^３ｂは、同一でも異なっていてもよい。）
　ならびに、
　有機酸、ヒドロキシアルキル尿素、多価アルコールもしくはそのアルキルエーテル体、および、ヒドロキシアルキルアミンから選ばれる少なくとも１種を含むことを特徴とする。 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 N—A ⁴ , and A ² , A ^3, and A ⁴ are each independently a hydrogen 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 It is 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 to 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 group 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 may be the same or different. (If t is an integer of 2 to 4, a plurality of X ^3b may be the same or different.)
And
It contains at least one selected from organic acids, hydroxyalkylureas, polyhydric alcohols or alkyl ethers thereof, and hydroxyalkylamines.

The composition for external use of the skin of the present invention contains the above benzylidene azolidine derivative or a salt thereof, and at least one selected from organic acids, hydroxyalkylureas, polyhydric alcohols or alkyl ethers thereof, and hydroxyalkylamines. As a result, the composition for external use on the skin with improved dissolution stability of the benzylidene azolidine derivative or a salt thereof is obtained.

The present invention also includes a method for improving the solubility of the benzylidene azolidine derivative or a salt thereof contained in the composition for external use on the skin.

In the composition for external use of the skin 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 functional group. The group (3) is preferred.

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 an alkyl group having 1 to 8 carbon atoms substituted with a hydrogen atom or a hydroxyl group, the functional group ( 1), the functional group (2), or the functional group (3).

　　（構造式（ＩＩ）中、ｎ´は、０～４の整数であり、ｎ´が１～４の整数である場合、複数存在するＡ^３－Ｏ－は、同一でも異なっていてもよい。） 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.

In the composition for external use of the skin of the present invention, as the organic acid, lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, Examples thereof include ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, derivatives thereof, and salts thereof. Of these, lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, and fumaric acid are preferable.

In the external composition for skin of the present invention, the hydroxyalkylurea includes methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea. 1-hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butyl Examples include urea, 2-hydroxy-t-butylurea, hydroxypentylurea, hydroxyhexylurea, hydroxyheptylurea, hydroxyoctylurea, dihydroxyethylurea, dihydroxypropylurea, dihydroxybutylurea and the like. Among them, methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxybutylurea, 2-hydroxybutylurea, 3- Hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2-hydroxy-t-butylurea, and these Derivatives or salts thereof are preferable.

In the external composition for skin of the present invention, the polyhydric alcohol or alkyl ether thereof may be 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol. 1,4-butylene glycol, 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, Pentanediol, hexanediol, heptanediol, octanediol, nonanediol, decanediol, ethanetriol, propanetriol, butanetriol, pentanetriol, hexanetriol, polyethylene glycol It can be mentioned Lumpur, glycerin, and di-glycerin. Among them, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, Propylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, and derivatives or salts thereof are preferable.

In the composition for external use of the skin of the present invention, the hydroxyalkylamine includes trimethanolamine, monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, lysine, and these Derivatives or salts thereof can be mentioned. Among them, tri (methanol) amine, tri (1-ethanol) amine, tri (2-ethanol) amine, tri (1-propanol) amine, tri (2-propanol) amine, tri (3-propanol) amine, etc. Tri (hydroxyalkyl) amine is preferred.

Further, in the external composition for skin of the present invention, the external composition for skin is preferably a water-soluble preparation such as an aqueous solution, aqueous suspension, aqueous emulsion, aqueous gel, aqueous lotion or the like.

The composition for external use of the skin of the present invention is characterized by containing at least one selected from organic acids, hydroxyalkylureas, polyhydric alcohols or alkyl ethers thereof, and hydroxyalkylamines, The organic acid, hydroxyalkylurea, polyhydric alcohol or alkyl ether thereof, and hydroxyalkylamine are also included in a case where a plurality of them are used in combination as appropriate. The organic acids, hydroxyalkylureas, polyhydric alcohols or their alkyl ethers, and hydroxyalkylamines are added mainly for the purpose of using other properties and characteristics different from the above acidic and basic properties. -Even if it is mix | blended, it is contained in the composition for skin external use of this invention.

(Second embodiment of the present invention)
In addition, as a result of intensive studies to solve the above-mentioned problems, the present inventors have succeeded in creating the following benzylidene azolidine derivatives or salts thereof, and for external use on the skin containing the above-mentioned compound, a glycol compound, and a hydroxyalkylurea. It has been found that the above object can be achieved by the composition, and the present invention has been completed.

　　（構造式（Ｉ）中、ｎは１～５の整数であり、Ａ^１は、Ｏ、Ｓ、またはＮ－Ａ^４であり、Ａ^２、Ａ^３およびＡ^４は、それぞれ独立に、水素原子、ヒドロキシル基で置換されていてもよい炭素数１～８のアルキル基、下記構造式（１）で表わされる官能基（１）、下記構造式（２）で表わされる官能基（２）、または下記構造式（３）で表わされる官能基（３）である（ただし、少なくともＡ^２、Ａ^３およびＡ^４のいずれかに１つ以上のヒドロキシル基を含むものとする）。また、ｎが２～５の整数である場合、複数存在するＡ^３－Ｏ－は、同一でも異なっていてもよい。）

　　（構造式（１）中、Ｘ^１は、炭素数２～４のアルキレン基であり、Ｒ^１は、炭素数２～４のヒドロキシアルキル基であり、ｍは、１～４の整数である。ｍが２～４の整数である場合、複数存在するＸ^１は、同一でも異なっていてもよい。）

　　（構造式（２）中、Ｘ^２は、炭素数２～４のアルキレン基であり、Ｒ^２は炭素数２～４のヒドロキシアルキル基であり、ｐは１または２であり、ｑは、０～４の整数であり、ｑが２～４の整数である場合、複数存在するＸ^２は、同一でも異なっていてもよい。）

　　（構造式（３）中、Ｘ^３ａおよびＸ^３ｂは、それぞれ独立に、炭素数２～４のアルキレン基であり、Ｒ^３ａおよびＲ^３ｂは、それぞれ独立に炭素数２～４のヒドロキシアルキル基であり、ｒは１または２であり、ｓおよびｔは、それぞれ独立に０～４の整数である。ｓが２～４の整数である場合、複数存在するＸ^３ａは、同一でも異なっていてもよいし、ｔが２～４の整数である場合、複数存在するＸ^３ｂは、同一でも異なっていてもよい。）
　（Ｂ）グリコール化合物、ならびに、（Ｃ）ヒドロキシアルキル尿素、ＨＬＢ値８以上の界面活性剤、水と混和性のある環状構造を有する有機溶剤、または、有機酸およびその誘導体、を含むことを特徴とする。 That is, the composition for external use of the skin of the present invention comprises (A) 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 N—A ⁴ , and A ² , A ^3, and A ⁴ are each independently a hydrogen 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 It is 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 to 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 group 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 may be the same or different. (If t is an integer of 2 to 4, a plurality of X ^3b may be the same or different.)
(B) a glycol compound, and (C) a hydroxyalkylurea, a surfactant having an HLB value of 8 or more, an organic solvent having a cyclic structure miscible with water, or an organic acid and a derivative thereof And

The composition for external use of the skin of the present invention is mixed with the above (A) benzylidene azolidine derivative or a salt thereof, the above (B) glycol compound, the above (C) hydroxyalkylurea, a surfactant having an HLB value of 8 or more, and water. By including an organic solvent having a cyclic structure or an organic acid and a derivative thereof, the composition for external use in skin is improved in dissolution stability of the benzylidene azolidine derivative or a salt thereof. Moreover, transparency can be improved by having the above-described configuration, and a preparation with higher transparency can be easily obtained as compared with the prior art.

The present invention also includes a method for improving the solubility of the benzylidene azolidine derivative or a salt thereof contained in the composition for external use on the skin. In the present invention, the term “derivative” means that one or more atoms in the chemical structure are replaced with other atoms or substituents.

In the external composition for skin 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 functional group The group (3) is preferred.

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 ( 1), the functional group (2), or the functional group (3) is preferable.

　　（構造式（ＩＩ）中、ｎ´は、０～４の整数であり、ｎ´が１～４の整数である場合、複数存在するＡ^３－Ｏ－は、同一でも異なっていてもよい。） 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.

In the external composition for skin of the present invention, the weight ratio of (B) to (C) in the external composition for skin is preferably 100: 1 to 0.01: 1, and 50: It may be 1 to 0.1: 1, 20: 1 to 0.5: 1, or 10: 1 to 1: 1. .

In the external composition for skin of the present invention, the glycol compound may be 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol. 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, 1,2-pentanediol, 1,3-pentanediol, 1,2-hexanediol, 1,3-hexanediol, hexylene glycol, heptanediol, octanediol, nonanediol, decanediol, polyethylene glycol, caprylyl glycol, and Is preferably at least one selected from these derivatives or salts thereof.

In the composition for external use of the skin of the present invention, it is preferable that (B) contains a glycol compound which is 1,2-diol.

In the composition for external use of the skin of the present invention, examples of the hydroxyalkylurea include methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea. 1-hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butyl Examples include urea, 2-hydroxy-t-butylurea, hydroxypentylurea, hydroxyhexylurea, hydroxyheptylurea, hydroxyoctylurea, dihydroxyethylurea, dihydroxypropylurea, dihydroxybutylurea and the like. Among them, methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxybutylurea, 2-hydroxybutylurea, 3- Hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2-hydroxy-t-butylurea, and these It is preferable that it is 1 or more types selected from derivatives or these salts.

In the external composition for skin of the present invention, the surfactant may be polyethylene glycol-40 hydrogenated castor oil, polyethylene glycol-50 hydrogenated castor oil, polyethylene glycol-60 hydrogenated castor oil, or polyethylene glycol-80 water. Castor oil added, polyethylene glycol-100 hydrogenated castor oil, polyethylene glycol-25 stearate, polyethylene glycol-40 stearate, polyethylene glycol stearate 45, polyethylene glycol stearate 55, polyoxyethylene polyoxypropylene cetyl ether ( 20E.O.) (4P.O.), polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (8P.O.), polyoxyethylene (21) lauryl ether, polyoxy Tylene (25) lauryl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (15) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl Ether, polyoxyethylene (30) cetyl ether, polyoxyethylene (40) cetyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (15) oleyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (50) oleyl ether, polyoxyethylene (20) behenyl ether, polyoxyethylene (30) behenyl ether, polysorbate 20, polysol Over preparative 40, polysorbate 60, is preferably at least one selected from polysorbate 80.

Further, in the composition for external use of the skin of the present invention, the organic solvent having a ring is N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, γ-butyrolactone, γ-butyrolactam, dimethylisosorbide, It is preferably at least one selected from sulfolane.

In the composition for external use of the skin of the present invention, the organic acid and its derivative are lactic acid, methyl lactate, ethyl lactate, propyl lactate, isopropyl lactate, butyl lactate, acetic acid, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, One or more selected from isobutyl acetate, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid It is preferable that

Moreover, in the composition for external use of the skin of the present invention, it is preferable that (B) contains two or more glycol compounds.

Further, in the external composition for skin of the present invention, the external composition for skin includes a hydrophilic composition such as an aqueous solution, aqueous suspension, aqueous emulsion, O / W type composition, aqueous gel, aqueous lotion and the like. It is preferable that it is a thing. In the skin external composition, the aqueous solvent is preferably water and / or an alcohol solvent. In the above-mentioned external composition for skin, the alcohol content in the composition is preferably 50% by weight or less, more preferably 30% by weight or less, and even 0.1 to 30% by weight. It may be 3 to 25% by weight, 5 to 20% by weight, or 10 to 15% by weight.

The composition for external use of the skin of the present invention improves the dissolution stability of a benzylidene azolidine derivative and a salt thereof, which is a novel hydrophilic and safe neutral compound having an ultraviolet absorbing action (particularly UVA absorbing action). be able to. More specifically, the solubility of the benzylidene azolidine derivative and its salt is improved, or the precipitation after being dissolved by vibration such as stirring, shaking, heating, ultrasonic treatment, etc. is reduced / suppressed. It can be made.

Moreover, the composition for external use of the skin of the present invention improves the dissolution stability of a benzylidene azolidine derivative and a salt thereof, which is a neutral compound having a UV absorption action (particularly UVA absorption action) and is safe for the skin. Can be made. More specifically, the solubility of the benzylidene azolidine derivative and its salt is improved, or the precipitation after being dissolved by vibration such as stirring, shaking, heating, ultrasonic treatment, etc. is reduced / suppressed. It can be made. In particular, it can be a composition for external use having improved solubility in a hydrophilic solvent, solubility after storage at low temperature, and transparency.

Photograph showing results of solubility evaluation in Examples Photograph showing results of solubility evaluation in Examples

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 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 organic acids 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 the present specification excluding the structural formula (I) and the structural formula (I), “n”, “A ¹ ”, “A ² ”, and “A ³ ” are defined as follows: Is done.

(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,,} from the viewpoint of being able to effectively absorb light in the wavelength region close to UVA and UVA, preferably a ^{N-A 4.}

(3) “A ² ”, “A ³ ” and “A ⁴ ”
A ² , A ³ and A ⁴ are each independently a hydrogen atom, an alkyl group having 1 to 8 carbon atoms which may be substituted with a hydroxyl group, or a functional group represented by the following structural formula (1) (functional group ( 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.

　　（構造式（１）中、Ｘ^１は、炭素数２～４のアルキレン基であり、Ｒ^１は、炭素数２～４のヒドロキシアルキル基であり、ｍは、１～４の整数である。ｍが２～４の整数である場合、複数存在するＸ^１は、同一でも異なっていてもよい。）

　（構造式（２）中、Ｘ^２は、炭素数２～４のアルキレン基であり、Ｒ^２は炭素数２～４のヒドロキシアルキル基であり、ｐは１または２であり、ｑは、０～４の整数であり、ｑが２～４の整数である場合、複数存在するＸ^２は、同一でも異なっていてもよい。）

　（構造式（３）中、Ｘ^３ａおよびＸ^３ｂは、それぞれ独立に、炭素数２～４のアルキレン基であり、Ｒ^３ａおよびＲ^３ｂは、それぞれ独立に炭素数２～４のヒドロキシアルキル基であり、ｒは１または２であり、ｓおよびｔは、それぞれ独立に０～４の整数である。ｓが２～４の整数である場合、複数存在するＸ^３ａは、同一でも異なっていてもよいし、ｔが２～４の整数である場合、複数存在するＸ^３ｂは、同一でも異なっていてもよい。） Also, in that it can improve UV ^absorption, of A 2, ^{A 3} and ^{A 4,} at least one said functional group (1), the functional group (2), or the certain functional group (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 (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 group 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 may be the same or different. (If 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 them, a linear or branched hydroxyalkyl group having 1 to 8 carbon atoms is preferable from the viewpoint of improving UV absorption and water hydrophilicity.

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 can be used widely. From the viewpoint that it can be produced from such a reagent 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 an integer of 1 to 2 from the viewpoint that a high specific absorbance (absorbance of ultraviolet rays per mass) can be exhibited and can be produced from a general-purpose reagent raw material. Is preferable, and 1 is more preferable.

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 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 ^3a and X ^3b are a methylene group (—CH ₂ —) or An ethylene group (—CH ₂ CH ₂ —) is preferred.

(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.

　（上記構造式（ＩＩ）中、ｎ´は、０～４の整数であり、ｎ´が１～４の整数である場合、複数存在するＡ^３－Ｏ－は、同一でも異なっていてもよい。Ａ^３は、水素原子、炭素数１～８の、ヒドロキシル基で置換されているアルキル基、官能基（１）、官能基（２）、または官能基（３）である。） 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.

Further, in the external composition for 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. 0.001% by weight or more and 5% by weight or less, 0.05% by weight or more and 3% by weight or less, or 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.

[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.

　（式（ｇ）のＡ^１は、式（Ｉ）のＡ^１と同一である。
　Ｚは、ヒドロキシル基またはアルコキシル基である。）

　（式（ｈ）のＡ^２は、式（Ｉ）のＡ^２と同一である。）

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).)

　（式（ｉ）のＹは、式（ｄ）のＹと同一であり、ｕは、１または２であり、Ｚは、ヒドロキシル基またはアルコキシル基である。）

　（式（ｊ）のｕは、１または２であり、Ｚは、ヒドロキシル基またはアルコキシル基である。）

　（式（ｋ）のｕは、１または２であり、Ｚは、ヒドロキシル基またはアルコキシル基である。） 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.

(First embodiment of the present invention)
[Organic acid]
The organic acid in this invention can use a well-known organic acid in the range which does not impair the effect of this invention.

The organic acid includes an organic substance having one or more acidic groups, a derivative thereof, or a salt thereof. Examples of the organic acid include lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethyl Examples thereof include sulfonic acid, derivatives thereof, and salts thereof. Moreover, the organic acid used as a pH adjuster can be mention | raise | lifted as said organic acid. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the organic acid is lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaprone. Acids and derivatives thereof, or salts thereof are preferable. Of these, lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, and fumaric acid are more preferable. Furthermore, lactic acid, glycolic acid, gluconic acid, and derivatives or salts thereof are even more preferable. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the content of the organic acid may be 0.00001 wt% or more and 90 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less, and 0 It may be 0.005% by weight or more and 10% by weight or less.

[Hydroxyalkylurea]
The hydroxyalkyl urea in this invention can use well-known hydroxyalkyl urea in the range which does not impair the effect of this invention.

The hydroxyalkylurea includes urea having one or more hydroxyalkyl groups and derivatives thereof or salts thereof. The hydroxyalkyl group is preferably substituted on a nitrogen atom. Examples of the hydroxyalkyl urea include methyl urea, 1-hydroxyethyl urea, 2-hydroxyethyl urea, 1-hydroxypropyl urea, 2-hydroxypropyl urea, 3-hydroxypropyl urea, 1-hydroxybutyl urea, 2- Hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2-hydroxy-t-butyl Urea, hydroxybutylurea, hydroxypentylurea, hydroxyhexylurea, hydroxyheptylurea, hydroxyoctylurea, dihydroxyethylurea, dihydroxypropylurea, dihydroxybutylurea and their derivatives or derivatives And La of salt can be mentioned. These may be used singly or in combination of two or more.

Specific examples of the hydroxyalkylurea and derivatives thereof include, for example, N- (trishydroxymethylmethyl) urea, N-ethyl-N ′-(2-hydroxyethyl) urea, N, N-bis- ( 2-hydroxyethyl) urea, N, N′-bis- (2-hydroxyethyl) urea, N- (2,3-dihydroxypropyl) urea, N- (2,3,4,5,6-pentahydroxyhexyl) ) Urea, N-methyl-N- (1,3,4,5,6-pentahydroxy-2-hexyl) urea, N-methyl-N ′-(1-hydroxy-2-methyl-2-propyl) urea N- (1-hydroxy-2-methyl-2-propyl) urea, N- (1,3-dihydroxy-2-propyl) urea, N, N-bis- (2-hydroxypropyl) urea, N, N '-Bi -(2-hydroxypropyl) urea, N, N-bis- (2-hydroxyethyl) -N'-propylurea, N, N-bis- (2-hydroxypropyl) -N '-(2-hydroxyethyl) Urea, Nt-butyl-N ′-(2-hydroxyethyl) -N ′-(2-hydroxypropyl) urea, N- (1,3-dihydroxy-2-propyl) -N ′-(2-hydroxy Ethyl) urea, N, N, -bis- (2-hydroxyethyl) -N ′, N′-dimethylurea, N, N, N ′, N′-tetrakis- (2-hydroxyethyl) urea, N ′, N′-bis- (2-hydroxyethyl) -N ′, N′-bis- (2-hydroxypropyl) urea and the like can also be mentioned. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the hydroxyalkylurea is methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxyurea. Hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2 -Hydroxy-t-butylurea and derivatives thereof or salts thereof are preferred. Among them, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea 4-hydroxybutylurea is more preferred. Furthermore, 1-hydroxyethyl urea, 2-hydroxyethyl urea, 1-hydroxypropyl urea, 2-hydroxypropyl urea, 3-hydroxypropyl urea are even more preferable. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylurea content may be 0.00001 wt% or more and 95 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. It may be 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less, It may be 0.005 wt% or more and 10 wt% or less.

[Polyhydric alcohol or its alkyl ether form]
As the polyhydric alcohol or the alkyl ether form thereof in the present invention, a known polyhydric alcohol or an alkyl ether form thereof can be used as long as the effects of the present invention are not impaired.

The polyhydric alcohol includes an organic substance having two or more hydroxyl groups, a derivative thereof, or a salt thereof. Examples of the polyhydric alcohol include 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, Propoxy diglycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, pentanediol, hexanediol, heptanediol, octanediol, nonanediol, decanediol, Examples thereof include ethanetriol, propanetriol, butanetriol, pentanetriol, hexanetriol, diglycerin, and derivatives or salts thereof. These may be used singly or in combination of two or more.

Further, the alkyl ether form of the polyhydric alcohol includes a compound in which one or more hydroxyl groups of the polyhydric alcohol are etherified, a derivative thereof, or a salt thereof. Examples of the alkyl ether of the polyhydric alcohol include, for example, a part of the polyhydric alcohol monomethyl ether, monoethyl ether, monopropyl ether, monobutyl ether, monopentyl ether, dimethyl ether, and diethyl ether. , Dipropyl ether form, dibutyl ether form and the like. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the polyhydric alcohol or an alkyl ether thereof is 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1, 4-butylene glycol, 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, propoxydiglycol , Isopropoxy diglycol, pentanediol, hexanediol, heptanediol, octanediol, nonanediol, decanediol, ethanetriol, propanetriol, butanetriol, pentanetrio , Hexane triol, polyethylene glycol, glycerin, diglycerin, and derivatives thereof, or, preferably a salt thereof. Among them, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, More preferred are propylene glycol, ethoxydiglycol, pentanediol, hexanediol, heptanediol, octanediol, polyethylene glycol, glycerin, and diglycerin. 1,2-butylene glycol, 1,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, pentanediol, hexanediol, glycerin, Diglycerin is even more preferred. Furthermore, 1,3-butylene glycol, 1,2-propylene glycol, dipropylene glycol, isopropylene glycol and ethoxydiglycol are particularly preferable. These compounds may be used alone or in combination of two or more.

In the composition for external use of the skin of the present invention, the content of the polyhydric alcohol or alkyl ether thereof can be 0.00001 wt% or more and 95 wt% or less, and 0.00005 wt% or more and 70 wt%. Or 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, or 0.001 wt% or more and 20 wt% or less. It may be 0.005% by weight or more and 10% by weight or less.

[Hydroxyalkylamine]
As the hydroxyalkylamine in the present invention, known hydroxyalkylamines can be used as long as the effects of the present invention are not impaired.

The above hydroxyalkylamine includes an amine compound having a hydroxyalkyl group, a derivative thereof, or a salt thereof. Examples of the hydroxyalkylamine include monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, lysine, and derivatives or salts thereof. . Moreover, the organic base used as a pH adjuster can be used as said hydroxyalkylamine. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylamine is tri (methanol) amine, tri (1-ethanol) amine, tri (2-ethanol) amine, tri (1-propanol) amine, tri (2-propanol). ) A tri (hydroxyalkyl) amine such as amine or tri (3-propanol) is preferred. Of these, tri (methanol) amine, tri (1-ethanol) amine, tri (2-ethanol) amine, and tri (2-propanol) amine are more preferable. Furthermore, tri (1-ethanol) amine and tri (2-ethanol) amine are even more preferable. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylamine content may be 0.00001 wt% or more and 95 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. It may be 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less, It may be 0.005 wt% or more and 10 wt% or less.

(Second embodiment of the present invention)

[Glycol compound]
The glycol compound in this invention can use a well-known glycol compound in the range which does not impair the effect of this invention.

The above glycol compound includes an organic substance having two hydroxyl groups, a derivative thereof, or a salt thereof. Examples of the glycol compound include 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, pentanediol (1,2-pentanediol, 1,3-pentane Diol), hexanediol (1,2-hexanediol, 1,3-hexanediol, etc.), hexylene glycol, heptanediol, octanediol, nonanediol, decanediol, polyethylene glycol, caprily Glycol, and it is preferably at least one selected from the derivatives thereof, or salts thereof. Among these, as (B), it is particularly preferable to include a glycol compound that is 1,2-diol.

In addition, in the composition for external use of the skin of the present invention, it is preferable that (B) contains two or more of the glycol compounds. Further, 1,3-butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, polyethylene glycol, pentanediol (1,2-pentanediol, 1,3-pentanediol, etc.), hexane More preferably, two or more diols (1,2-hexanediol, 1,3-hexanediol, etc.) are selected.

In the composition for external use of the skin of the present invention, the content of the glycol compound may be 0.00001 wt% or more and 95 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 25 wt% or less, and 0 It may be 0.003 wt% or more and 20 wt% or less, or 0.005 wt% or more and 10 wt% or less.

[Hydroxyalkylurea]
The hydroxyalkyl urea in this invention can use well-known hydroxyalkyl urea in the range which does not impair the effect of this invention.

The hydroxyalkylurea includes urea having one or more hydroxyalkyl groups and derivatives thereof or salts thereof. The hydroxyalkyl group is preferably substituted on a nitrogen atom. Examples of the hydroxyalkyl urea include methyl urea, 1-hydroxyethyl urea, 2-hydroxyethyl urea, 1-hydroxypropyl urea, 2-hydroxypropyl urea, 3-hydroxypropyl urea, 1-hydroxybutyl urea, 2- Hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2-hydroxy-t-butyl Urea, hydroxybutylurea, hydroxypentylurea, hydroxyhexylurea, hydroxyheptylurea, hydroxyoctylurea, dihydroxyethylurea, dihydroxypropylurea, dihydroxybutylurea and their derivatives or derivatives And La of salt can be mentioned. These may be used singly or in combination of two or more.

Specific examples of the hydroxyalkylurea and derivatives thereof include, for example, N- (trishydroxymethylmethyl) urea, N-ethyl-N ′-(2-hydroxyethyl) urea, N, N-bis- ( 2-hydroxyethyl) urea, N, N′-bis- (2-hydroxyethyl) urea, N- (2,3-dihydroxypropyl) urea, N- (2,3,4,5,6-pentahydroxyhexyl) ) Urea, N-methyl-N- (1,3,4,5,6-pentahydroxy-2-hexyl) urea, N-methyl-N ′-(1-hydroxy-2-methyl-2-propyl) urea N- (1-hydroxy-2-methyl-2-propyl) urea, N- (1,3-dihydroxy-2-propyl) urea, N, N-bis- (2-hydroxypropyl) urea, N, N '-Bi -(2-hydroxypropyl) urea, N, N-bis- (2-hydroxyethyl) -N'-propylurea, N, N-bis- (2-hydroxypropyl) -N '-(2-hydroxyethyl) Urea, Nt-butyl-N ′-(2-hydroxyethyl) -N ′-(2-hydroxypropyl) urea, N- (1,3-dihydroxy-2-propyl) -N ′-(2-hydroxy Ethyl) urea, N, N, -bis- (2-hydroxyethyl) -N ′, N′-dimethylurea, N, N, N ′, N′-tetrakis- (2-hydroxyethyl) urea, N ′, N′-bis- (2-hydroxyethyl) -N ′, N′-bis- (2-hydroxypropyl) urea and the like can also be mentioned. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the hydroxyalkylurea is methylurea, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxyurea. Hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2 -Hydroxy-t-butylurea and derivatives thereof or salts thereof are preferred. Among them, 1-hydroxyethylurea, 2-hydroxyethylurea, 1-hydroxypropylurea, 2-hydroxypropylurea, 3-hydroxypropylurea, 1-hydroxybutylurea, 2-hydroxybutylurea, 3-hydroxybutylurea 4-hydroxybutylurea is more preferred. Furthermore, 1-hydroxyethyl urea, 2-hydroxyethyl urea, 1-hydroxypropyl urea, 2-hydroxypropyl urea, 3-hydroxypropyl urea are even more preferable. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylurea content may be 0.00001 wt% or more and 95 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. It may be 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 25 wt% or less, It may be 0.003 wt% or more and 20 wt% or less, or 0.005 wt% or more and 10 wt% or less.

In the external composition for skin of the present invention, the weight ratio of the glycol compound to the hydroxyalkylurea in the external composition for skin is preferably 100: 1 to 0.01: 1, and 50: 1. It may be ˜0.1: 1, 20: 1 to 0.5: 1, or 10: 1 to 1: 1. By making it within the above weight ratio range, the solubility of the benzylidene azolidine derivative and its salt is more effectively improved, or once dissolved by vibration such as stirring, shaking, heating, sonication, etc. It is possible to reduce or suppress the precipitation after the deposition.

In the external composition for skin of the present invention, the viscosity of the external composition for skin is preferably 1,000 to 200,000 (unit: mPas), may be 3000 to 100,000, and may be 5000 to 70,000. It may be 10,000 to 50,000. By setting the weight ratio within the above range, the composition can be easily spread on the skin, and dripping from the container mouth can be suppressed. Moreover, the viscosity in this invention means the value when a formulation is put into a glass-made 50 mL screw mouth bottle, and it measures after 1 minute progress from a rotation start at 25 degreeC with a BL type viscometer and M4 rotor at a rotational speed of 6 rpm.

[Surfactant]
In the external composition for skin of the present invention, a known surfactant can be used as long as the effects of the present invention are not impaired.

The surfactant preferably has a hydrophilic-lipophilic balance (HLB) value of 8 or more, and the upper limit is not particularly limited, but usually about 8 to 16 is used. Surfactants are distinguished from nonionic surfactants, cationic surfactants, anionic surfactants, and zwitterionic surfactants depending on the ionization of hydrophilic groups. Any of the surfactants used in the composition for external skin of the present invention may be used, but from the viewpoint that the effects of the present invention can be more reliably and easily exhibited, preferably a nonionic surfactant is used. Used.

The hydrophilic-lipophilic balance (HLB) value in the present invention is calculated by Kawakami's formula (following (Formula 1) using the hydrophilic group molecular weight (Mw) and lipophilic group molecular weight (MO) of the surfactant molecule. ).
HLB value = 7 + 11.7logMw / Mo (Formula 1)

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 such as: glyceryl monostearate, glyceryl fatty acid such as glyceryl monostearate malate; polyglyceryl fatty acids such as polyglyceryl monostearate, polyglyceryl monoisostearate, polyglyceryl diisostearate; propylene monostearate Propylene glycol fatty acid esters such as glycol; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene Hydrogenated castor oil derivatives such as hydrogenated 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 monooleate (20) sorbitan (polysorbate 80), polyoxyethylene (20) sorbitan isostearate Polyoxyethylene glycerin fatty acid esters; sucrose fatty acid esters; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyethylene cetyl ester Polyoxyalkylene alkyl ethers such as tellurium; Fatty acid polyoxyalkylene alkyl ethers such as fatty acid polyoxyethylene alkyl ether; Fatty acid polyethylene glycol; Amines such as stearylamine and oleylamine; Polyoxyethylene methylpolysiloxane copolymer Silicone surfactants such as polyether-modified silicones such as polyoxyethylene / polyoxypropylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone, etc. I can give you. These compounds may be used alone or in combination of two or more.

Among these, as the surfactant, polyethylene glycol-40 hydrogenated castor oil, polyethylene glycol-50 hydrogenated castor oil, polyethylene glycol-60 hydrogenated castor oil, polyethylene glycol-80 hydrogenated castor oil, polyethylene glycol-100 water. Castor oil, polyethylene glycol-25 stearate, polyethylene glycol-40 stearate, polyethylene glycol stearate 45, polyethylene glycol stearate 55, polyoxyethylene polyoxypropylene cetyl ether (20EO) (4PO .), Polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (8PO), polyoxyethylene (21) lauryl ether, polyoxyethylene (25) lauryl ether , Polyoxyethylene (10) cetyl ether, polyoxyethylene (15) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, polyoxyethylene ( 30) Cetyl ether, polyoxyethylene (40) cetyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (15) oleyl ether, polyoxyethylene (20) oleyl ether, Polyoxyethylene (50) oleyl ether, polyoxyethylene (20) behenyl ether, polyoxyethylene (30) behenyl ether, polysorbate 20, polysorbate 40, polysorbate 60 It is preferable to use one or more selected from polysorbate 80. These compounds may be used alone or in combination of two or more.

In the composition for external use of the skin of the present invention, the content of the surfactant may be 0.00001 wt% or more and 90 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. It may be 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less, It may be 0.005 wt% or more and 10 wt% or less.

In the external composition for skin of the present invention, the weight ratio of the glycol compound to the surfactant in the external composition for skin is preferably 100: 1 to 0.01: 1, and 50: 1. It may be ˜0.1: 1, 20: 1 to 0.5: 1, or 10: 1 to 1: 1. By making it within the above weight ratio range, the solubility of the benzylidene azolidine derivative and its salt is more effectively improved, or once dissolved by vibration such as stirring, shaking, heating, sonication, etc. It is possible to reduce or suppress the precipitation after the deposition.

[Organic solvent having a cyclic structure]
In the external composition for skin of the present invention, a known organic solvent having a cyclic structure miscible with water can be used as long as the effects of the present invention are not impaired.

Examples of the organic solvent having a cyclic structure include N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, γ-butyrolactone, γ-butyrolactam, dimethylisosorbide, and sulfolane. These may be used singly or in combination of two or more.

In addition, the organic solvent miscible with water in the present invention refers to an organic solvent having a property of mixing with water and forming a uniform layer without being separated into multiple layers when mixed with water at an arbitrary ratio. .

In the composition for external use of the skin of the present invention, the content of the organic solvent having the cyclic structure may be 0.00001 wt% or more and 90 wt% or less, and 0.00005 wt% or more and 70 wt% or less. 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less. It may be 0.005 wt% or more and 10 wt% or less.

In the external composition for skin of the present invention, the weight ratio of the glycol compound to the organic solvent having a cyclic structure in the external composition for skin is preferably 100: 1 to 0.01: 1. It may be 50: 1 to 0.1: 1, 20: 1 to 0.5: 1, or 10: 1 to 1: 1. By making it within the above weight ratio range, the solubility of the benzylidene azolidine derivative and its salt is more effectively improved, or once dissolved by vibration such as stirring, shaking, heating, sonication, etc. It is possible to reduce or suppress the precipitation after the deposition.

[Organic acid]
In the external composition for skin of the present invention, known organic acids and derivatives thereof can be used as long as the effects of the present invention are not impaired.

The organic acid and derivatives thereof include organic substances having one or more acidic groups and derivatives or salts thereof. Examples of the organic acid include lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, In addition, derivatives thereof, salts thereof, and the like can be given. Moreover, the organic acid used as a pH adjuster can be mention | raise | lifted as said organic acid. These may be used singly or in combination of two or more.

In the external composition for skin of the present invention, the organic acid is lactic acid, methyl lactate, ethyl lactate, propyl lactate, isopropyl lactate, butyl lactate, acetic acid, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, citric acid And at least one selected from tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, and aminoethylsulfonic acid. preferable. These may be used singly or in combination of two or more.

In the composition for external use of the skin of the present invention, the content of the organic acid and the derivative thereof can be 0.00001 wt% or more and 90 wt% or less, and is 0.00005 wt% or more and 70 wt% or less. 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, or 0.001 wt% or more and 20 wt% or less. It may be 0.005 wt% or more and 10 wt% or less.

In the external composition for skin of the present invention, the weight ratio of the glycol compound to the organic acid and derivatives thereof in the external composition for skin is preferably 100: 1 to 0.01: 1, : 1 to 0.1: 1, 20: 1 to 0.5: 1, or 10: 1 to 1: 1. By making it within the above weight ratio range, the solubility of the benzylidene azolidine derivative and its salt is more effectively improved, or once dissolved by vibration such as stirring, shaking, heating, sonication, etc. It is possible to reduce or suppress the precipitation after the deposition.

[Hydroxyalkylamine]
In the external composition for skin of the present invention, a known hydroxyalkylamine can be used as long as the effects of the present invention are not impaired.

The above hydroxyalkylamine includes an amine compound having a hydroxyalkyl group, a derivative thereof, or a salt thereof. Examples of the hydroxyalkylamine include monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, lysine, and derivatives or salts thereof. . Moreover, the organic base used as a pH adjuster can be used as said hydroxyalkylamine. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylamine is tri (methanol) amine, tri (1-ethanol) amine, tri (2-ethanol) amine, tri (1-propanol) amine, tri (2-propanol). ) A tri (hydroxyalkyl) amine such as amine or tri (3-propanol) is preferred. Of these, tri (methanol) amine, tri (1-ethanol) amine, tri (2-ethanol) amine, and tri (2-propanol) amine are more preferable. Furthermore, tri (1-ethanol) amine and tri (2-ethanol) amine are even more preferable. These may be used singly or in combination of two or more.

In the skin external composition of the present invention, the hydroxyalkylamine content may be 0.00001 wt% or more and 95 wt% or less, and may be 0.00005 wt% or more and 70 wt% or less. It may be 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, 0.001 wt% or more and 20 wt% or less, It may be 0.005 wt% or more and 10 wt% or less.

(Other components and formulation forms in the present invention)

[Acrylic acid compound]
In the composition for external use of the present invention, a known acrylic acid compound (a compound derived from acrylic acid) can be further used in order to improve the feeling of use within the range not impairing the effects of the present invention.

Examples of the acrylic acid-based compound include acrylic acid, methacrylic acid, acrylic acid alkyl methacrylate copolymer, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, poly (meth) acrylic acid, and poly (meth) acrylic. Sodium salt, (meth) acrylic acid / alkyl (meth) acrylate copolymer, (meth) acrylic acid / alkyl (meth) acrylate copolymer, (meth) acrylic acid / (meth) acrylamide / dimethyldiallylammonium chloride A copolymer, polyethyl (meth) acrylate, poly (meth) acrylamide, etc. can be mentioned. The (meth) acryl includes both acryl and methacryl.

[Preservative]
In the external composition for skin of the present invention, known preservatives (including preservatives) can be used as long as the effects of the present invention are not impaired.

Examples of the preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, Benzoic acids such as methyl paraoxybenzoate, phenoxyethanol, parabens, chlorobutanol, propynyl butylcarbamate, methylisothiazolinone, hinokitiol, chlorphenesine, chlorhexidine, benzalkonium chloride, benzethonium chloride, triclosan, sorbic acid, Examples include capryl hydroxamic acid. Of these, methyl paraoxybenzoate, propyl paraoxybenzoate, and phenoxyethanol are preferable.

[Polyhydric alcohol or its alkyl ether form]
As the polyhydric alcohol or the alkyl ether form thereof in the present invention, a known polyhydric alcohol or an alkyl ether form thereof can be used as long as the effects of the present invention are not impaired.

The polyhydric alcohol includes organic substances having three or more hydroxyl groups other than the glycol compound, and derivatives or salts thereof. Examples of the polyhydric alcohol include ethanetriol, propanetriol, butanetriol, pentanetriol, hexanetriol, glycerin, diglycerin, and derivatives or salts thereof. These may be used singly or in combination of two or more.

Further, the alkyl ether form of the polyhydric alcohol includes a compound in which one or more hydroxyl groups of the polyhydric alcohol are etherified, a derivative thereof, or a salt thereof. Examples of the alkyl ether of the polyhydric alcohol include, for example, a part of the polyhydric alcohol monomethyl ether, monoethyl ether, monopropyl ether, monobutyl ether, monopentyl ether, dimethyl ether, and diethyl ether. , Dipropyl ether form, dibutyl ether form and the like. These may be used singly or in combination of two or more.

In the composition for external use of the skin of the present invention, the content of the polyhydric alcohol or alkyl ether thereof can be 0.00001 wt% or more and 95 wt% or less, and 0.00005 wt% or more and 70 wt%. Or 0.0001 wt% or more and 50 wt% or less, 0.0005 wt% or more and 30 wt% or less, or 0.001 wt% or more and 20 wt% or less. It may be 0.005% by weight or more and 10% by weight or less.

(Other ingredients, formulation form)
[Additive]
In the present invention, the composition for external use for skin is a known additive added to cosmetics and quasi drugs, for example, thickeners, surfactants, preservatives, etc., as long as the effects of the present invention are not impaired. PH adjusters, chelating agents, stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, pearl luster imparting 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 thickener include cellulose-based thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, guar gum, locust bean gum, carrageenan, and xanthan gum. Such as polysaccharide thickener, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, dextrin fatty acid ester, pectin, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer , Dimethyl distearyl ammonium hectorite, (Royldimethyltaurine ammonium / vinyl pyrrolidone) copolymer, polyethylene glycol distearate, ethylene glycol triisostearate, polyoxyethylene (20) methylglucoside, triisostearate, polyethylene glycol, bentonite, alginic acid, sodium alginate, propylene glycol alginate, macrogol And water-soluble polymers such as sodium chondroitin sulfate, hyaluronic acid and salts thereof, hyaluronic acid derivatives and salts thereof.

Among these, in terms of particularly good usability, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, cellulose thickeners such as carboxyethyl cellulose, guar gum, locust bean gum, Carrageenan, thickening polysaccharides such as xanthan gum, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, dextrin fatty acid ester, pectin, (hydroxyethyl acrylate / acryloyldimethyl) Taurine Na) copolymer, dimethyl distearyl ammonium hex tri , (Acryloyl dimethyl taurate ammonium / vinyl pyrrolidone) copolymers are preferred, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, xanthan gum, alkyl methacrylate methacrylate, More preferred are hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer and (acryloyldimethyltauronium ammonium / vinylpyrrolidone) copolymer.

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 the skin is an antioxidant component, an anti-aging component, an anti-inflammatory component, a whitening component, a keratin softening component, a cell activation component, vitamins, blood circulation promotion, as long as the effects of the present invention are not hindered. Other ingredients that can be added to cosmetics and quasi-drugs, such as ingredients, moisturizing ingredients, ingredients that prevent and / or repair DNA damage, UV absorbing ingredients, UV scattering ingredients, cleaning ingredients, antibacterial ingredients, and astringent ingredients An active ingredient can be blended. Other active ingredients can be used singly or in combination of two or more.

Antioxidant components include components derived from plants (eg, grapes, ginseng, comfrey, etc.); proanthocyanidins, tocopherols and derivatives thereof, ascorbic acid and derivatives thereof, hesperidin, glucosyl hesperidin, ergothioneine, sodium bisulfite, erythorbine Examples thereof include acids and salts thereof, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, and hypotaurine. Among them, grape seed extract, grape leaf extract, ginseng extract, comfrey leaf extract, proanthocyanidins, tocopherol and its derivatives (particularly δ-tocopherol, α-tocopherol), ascorbic acid and its derivatives (particularly ascorbic acid, ascorbine) Preferred are sodium acid phosphate sodium, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), hesperidin, glucosyl hesperidin, and ergothioneine.

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.

Anti-inflammatory components include components derived from plants (eg Comfrey); allantoin, calamine, glycyrrhizic acid or derivatives thereof, glycyrrhetinic acid or derivatives thereof, zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin And salicylic acid or a derivative thereof. Of these, Comfrey leaf extract, allantoin, dipotassium glycyrrhizinate, and stearyl glycyrrhetinate are preferable.

Examples of the whitening component include arbutin; hydroquinone; kojic acid; ellagic acid; phytic acid; lucinol; chamomile ET; ascorbic acid or a derivative thereof; vitamin E or a derivative thereof; pantothenic acid or a derivative thereof; Plant components (for example, plant extracts and essential oils) having Among them, arbutin, hydroquinone, kojic acid, ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), 2-O-ethylascorbic acid, 3 -O-ethyl ascorbic acid, ascorbic acid glucoside and tranexamic acid 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, isocitric acid, ferulic 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, flavi Vitamin B2 such as adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate; nicotinic acids such as methyl nicotinate, nicotinic acid, nicotinamide; stearic acid Ascorbyl, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbic acid Vitamin Cs such as glucoside, 2-O-ethylascorbic acid, 3-O-ethylascorbic acid; methyl hesperidin, ergocar Vitamin Ds such as cipherol 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 monophosphate; Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, pyridoxamine hydrochloride, cyanocobalamin, hydride Vitamin B12 such as xoxocobalamin, deoxyadenosylcobalamin; folic acid such as folic acid, pteroylglutamic acid; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethein, D-panthetin, coenzyme A, Examples include 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 preferable.

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; polymers having a phospholipid polar group such as MPC polymer (for example, LIPIDURE ™); polyoxypropylene methylglucoside; trimethylglycine (betaine); hydroxyethyl Examples include urea; acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer; sorbitol and the like. Among them, chigaya root extract, hydrolyzed collagen, hydrolyzed elastin, MPC polymer glycerin, 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 glycerin (for example, Wilbride (trademark) S-753 (manufactured by NOF Corporation)), trimethylglycine (betaine), hydroxyethylurea, acrylic acid / acrylamide / Preferred are dimethyldiallylammonium chloride copolymer, hydrogenated lecithin, hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, and sorbitol.

Examples of the component having an action of preventing and / or repairing DNA damage include components derived from animals (eg, Artemia); components derived from plants (eg, cat's claw); DNA, DNA salts, RNA, RNA salts, etc. Nucleic acid components can be mentioned. Of these, artemia extract and DNA-Na are preferable.

UV-absorbing components include 2-ethylhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) ) Anilino] -1,3,5-triazine, dimethoxybenzylideneoxoimidazolidinepropionate 2-ethylhexyl, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine and the like can be mentioned. Among them, paramethoxycinnamate 2-ethylhexyl, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] 1,3,5-triazine is preferred.

In addition, as the ultraviolet absorbing component, a raw material to which one or more of the above ultraviolet absorbers are modified in formulation such as encapsulating in a microcapsule can 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 with an average particle size of 0.4 to 10 μm (for example, capsules containing ultraviolet absorbers described in JP-A-2009-167168) and other commercially available products (for example, Eusolex UV-Pearls OB-S (trade name), Eusolex UV-Pearls OB-S2 (trade name); manufactured by Merck & Co., Ltd., Silomama series (trade name); manufactured by Seiwa Kasei Co., Ltd., etc.) may be used.

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 water-containing silicic acid, aluminum hydroxide, coated with inorganic powder such as mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene, nylon, etc. 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 , Nonionic surfactants such as polyoxyalkylene hydrogenated castor oil; mono- or di-long-chain alkyl groups having a linear or branched long-chain alkyl group to which alkylene oxide may be added Cationic surfactants such as grade 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 present invention, the form of the external composition for skin is not particularly limited, and can take a form known as a form of cosmetics or quasi drugs. As such known forms, for example, liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, powders, poultices, non-woven 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 preparation). Formulation forms of emulsions, aqueous gels, jelly-like cosmetics and aqueous lotions are suitable. Further, depending on the formulation, an oil-in-water type (O / W), a water-in-oil type (W / O) or the like can be appropriately selected according to the purpose of use and the desired feeling of use.

The aqueous gel preparation in the present invention is generally called gel or jelly, and during use, dripping from the container mouth or the like, or flowing down on the skin that is the application site, is suppressed, and it is applied at the application site. It refers to a preparation with moderate viscosity and flexibility to spread. As a guideline, the viscosity of the external preparation for skin is 5000 to 70000 mPas and the amount of water in the preparation is 20 to 95% by weight. However, it can be set appropriately even if it is outside this range in consideration of the feeling of use and the stability of the preparation. is there.

Moreover, the pH of the composition for external use in the present invention can be appropriately set in consideration of the stability of the components to be blended. The standard is pH 2 to 9, more preferably pH 3 to 8, but it can be appropriately set even outside this range in consideration of the dosage form of the preparation and the 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 (organic acid, hydroxyalkylurea, polyhydric alcohol or alkyl ether thereof, and , Hydroxyalkylamine) may be 0.00001 wt% or more and 100 wt% or less, may be 0.00005 wt% or more and 80 wt% or less, and may be 0.0001 wt% or more and 50 wt% or less. % By weight or less, 0.0005% to 30% by weight, 0.001% to 20% by weight, 0.005% to 10% by weight Or may be 0.01 wt% or more and 5 wt% or less, 0.05 wt% or more and 3 wt% or less, May also be wt% or more than 1% by weight, it may be 0.5 wt% or less than 0.01 wt%.

In addition, as a method for preparing / manufacturing the skin external composition, for example, it is preferable to include a step of once heating the skin external composition to 50 ° C. or higher. Moreover, in the step of heating, for example, a step of 60 ° C. or higher, a step of 65 ° C. or higher, a step of 70 ° C. or higher, a step of 75 ° C. or higher, or a step of 80 ° C. or higher may be used. . By using the composition for external use of the skin of the present invention, it becomes possible to stably dissolve the amount of the benzylidene azolidine derivative which is difficult to dissolve at room temperature, or to reduce / suppress reprecipitation.

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).

(First embodiment)
<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: A 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 amount of dipropylene glycol, ethanol, and purified water is 100 (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.

　５－［４－［２－（２－ヒドロキシエトキシ）エトキシ］ベンジリデン］－３－［２－（２－ヒドロキシエトキシ）エチル］ヒダントイン（化合物（１）） 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 6, Comparative Example 1]
(Test Example 1: Solubility evaluation 1)
Samples prepared based on the formulation shown in Table 1 below were filled in 2 mL each in a Marm screw vial, and the compound (1) was dissolved in a water bath heated to 80 ° C. Then, after leaving still with a 25 degreeC thermostat for 24 hours, photography and observation of the sample were performed visually and the solubility of compound (1) was evaluated.

　　エタノールに溶解させた比較例１では、２４時間静置後に化合物（１）が析出していた。一方、実施例１～６では、溶液は澄明な外観を保っていた。よって、上記多価アルコール等を併用することにより、化合物（１）が安定に溶解されることが確認できた。 The obtained results are shown in Table 1 and FIGS.

In Comparative Example 1 dissolved in ethanol, the compound (1) was precipitated after standing for 24 hours. On the other hand, in Examples 1 to 6, the solution maintained a clear appearance. Therefore, it was confirmed that the compound (1) was stably dissolved by using the polyhydric alcohol or the like together.

[Examples 7 to 12, Comparative Example 2]
(Test Example 2: Solubility evaluation 2)
Samples prepared based on the formulation shown in Table 2 below were filled in 2 mL each in a Marm screw vial, and the compound (1) was dissolved in a water bath heated to 80 ° C. Then, after leaving still with a 25 degreeC thermostat for 24 hours, photography and observation of the sample were performed visually and the solubility of compound (1) was evaluated.

　　試験例１と同様に、表２の濃度組成においても、上記多価アルコール等を併用することにより、化合物（１）が安定に溶解されることが確認できた。 The obtained results are shown in Table 2.

Similarly to Test Example 1, it was confirmed that the compound (1) was stably dissolved by using the polyhydric alcohol or the like in combination with the concentration composition shown in Table 2.

[Examples 13 to 21, Comparative Examples 3 and 4]
(Test Example 3: Solubility evaluation 3)
Samples prepared based on the formulation shown in Table 3 below were filled in 2 mL each in a Marm screw vial, and the compound (1) was dissolved in a water bath heated to 80 ° C. Then, after leaving still with a 25 degreeC thermostat for 24 hours, photography and observation of the sample were performed visually and the solubility of compound (1) was evaluated.

　化合物（１）に上記有機酸等を配合した各実施例において、２４時間静置後に析出物は認められなかった。よって、上記有機酸等を併用することにより、化合物（１）が安定に溶解されることが確認できた。 The obtained results are shown in Tables 3 and 4.

In each Example in which the above organic acid or the like was blended with compound (1), no precipitate was observed after standing for 24 hours. Therefore, it was confirmed that the compound (1) was stably dissolved by using the organic acid or the like together.

[Examples 22 to 25, Comparative Example 5]
(Test Example 4: Solubility evaluation 4)
Samples prepared based on the formulation shown in Table 5 below were filled in 2 mL each in a Marm screw vial, and the compound (1) was dissolved in a water bath heated to 80 ° C. Then, after leaving still for 24 hours and 7 days with a 25 degreeC thermostat, the sample was observed visually and the solubility of compound (1) was evaluated.

　化合物（１）に上記多価アルコールを配合した各実施例において、２４時間静および７日間置後に析出物は認められなかった。よって、上記多価アルコール等を併用することにより、化合物（１）が安定に溶解されることが確認できた。 The results obtained are shown in Table 5.

In each Example in which the above polyhydric alcohol was blended with the compound (1), no precipitate was observed after standing for 24 hours and after standing for 7 days. Therefore, it was confirmed that the compound (1) was stably dissolved by using the polyhydric alcohol or the like together.

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

(Second embodiment)

<Transparency evaluation>
The obtained compound (1) was dissolved in a test solvent having each formulation shown in Table 1, and property confirmation immediately after adjustment at 25 ° C. and property confirmation after standing at 4 ° C. for 24 hours were evaluated.
In addition, transparency evaluation was performed by the presence or absence of visual precipitation.

(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.

　５－［４－［２－（２－ヒドロキシエトキシ）エトキシ］ベンジリデン］－３－［２－（２－ヒドロキシエトキシ）エチル］ヒダントイン（化合物（１）） 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).

Examples and comparative examples
The test solution was adjusted and the transparency was evaluated according to the formulation shown in Table 1 below.

　上述のように、比較例２、３においては、調整直後の溶解性は良好ではあったが、低温保管時においては析出物が発生した。一方、比較例１では同条件下でこの析出物が観察されなかったことから、上記析出物はベンジリデンアゾリジン誘導体であると解される。
　他方、上記ベンジリデンアゾリジン誘導体の析出に対して、上記組成物中にグルコール化合物およびヒドロキシエチルウレアを併せて配合した実施例１～３においては、調整直後の良好な溶解性とともに、低温保管時においても上記析出物の発生が認められなかった。 The results obtained are shown in Tables 1-7.

As described above, in Comparative Examples 2 and 3, the solubility immediately after the adjustment was good, but precipitates were generated during low-temperature storage. On the other hand, in Comparative Example 1, since this precipitate was not observed under the same conditions, it is understood that the precipitate is a benzylidene azolidine derivative.
On the other hand, in Examples 1 to 3, in which the benzylidene azolidine derivative was combined with a glycol compound and hydroxyethylurea in the above composition in combination with the good solubility immediately after the adjustment and during low-temperature storage. Also, the occurrence of the above precipitate was not observed.

　上記表２、３の配合に従って試験液の調整を行った。得られた各製剤は析出もなく、安定に溶解し、かつ、４℃、２４時間静置後においても、透明性が高い製剤が得られた。

The test solution was adjusted according to the formulations shown in Tables 2 and 3 above. Each of the obtained preparations did not precipitate, dissolved stably, and a highly transparent preparation was obtained even after standing at 4 ° C. for 24 hours.

　上記表４～７の配合に従って試験液の調整を行った。得られた各製剤は析出もなく、安定に溶解し、かつ、４℃、２４時間静置後においても、透明性が高い製剤が得られた。

The test solutions were adjusted according to the formulations shown in Tables 4-7. Each of the obtained preparations did not precipitate, dissolved stably, and a highly transparent preparation was obtained even after standing at 4 ° C. for 24 hours.

Thus, by using the composition for external use of the skin of the present invention, it was confirmed that the compound (1) was stably dissolved even at low temperature storage, as well as excellent solubility immediately after preparation.

　表中の紫外線吸収剤内包カプセルとは、紫外線吸収剤としてパラメトキシケイ皮酸２－エチルヘキシル、２－［４－（ジエチルアミノ）－２－ヒドロキシベンゾイル］安息香酸ヘキシルエステル、ｔ－ブチルメトキシジベンゾイルメタン、もしくはオクトクリレンを、スチレンおよびその誘導体、もしくは（メタ）アクリル酸およびその誘導体を原料をするマイクロカプセルに内包したものである。 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 (26)

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 N—A ⁴ , and A ² , A ^3, and A ⁴ are each independently a hydrogen 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 It is 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 to 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 group 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 may be the same or different. (If 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 one or more selected from organic acids, hydroxyalkylureas, polyhydric alcohols or alkyl ethers thereof, and hydroxyalkylamines. 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. 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 composition for external use on skin according to claim 1 or 2, wherein the composition is the functional group (3). 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 organic acid is lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, The skin external composition according to any one of claims 1 to 5, which is one or more selected from derivatives or salts thereof. The polyhydric alcohol or alkyl ether thereof is 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3- Butylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, pentanediol, hexanediol, heptanediol, octanediol, Nonanediol, decanediol, ethanetriol, propanetriol, butanetriol, pentanetriol, hexanetriol, polyethylene glycol, glycerin, diglycerin, and It is one or more selected from these derivatives or salts thereof, the skin external composition according to any one of claims 1 to 5. The hydroxyalkylamine is selected from trimethanolamine, monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, lysine, and derivatives or salts thereof 1 The external composition for skin according to any one of claims 1 to 5, wherein the composition is one or more species. (A) 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 N—A ⁴ , and A ² , A ^3, and A ⁴ are each independently a hydrogen 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 It is 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 to 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 group 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 may be the same or different. (If t is an integer of 2 to 4, a plurality of X ^3b may be the same or different.)
(B) a glycol compound, and (C) a hydroxyalkylurea, a surfactant having an HLB value of 8 or more, an organic solvent having a cyclic structure miscible with water, or an organic acid and a derivative thereof A composition for external use on the skin. 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 composition for external use of skin according to claim 9. 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 composition for external use on skin according to claim 9 or 10, wherein the functional group (3) is used. The skin external composition according to any one of claims 9 to 11, 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 9 to 12, wherein the structural formula (I) is a benzylidenehydantoin derivative represented by the following structural formula (III) or a salt thereof.

14. The external composition for skin according to any one of claims 9 to 13, wherein the weight ratio of (B) to (C) in the external composition for skin is 100: 1 to 0.01: 1. The glycol compound is 1,1-ethylene glycol, 1,2-ethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, 1,2 -Propylene glycol, 1,3-propylene glycol, dipropylene glycol, isopropylene glycol, ethoxydiglycol, propoxydiglycol, isopropoxydiglycol, pentanediol, hexanediol, hexyleneglycol, heptanediol, octanediol, nonanediol The external composition for skin according to any one of claims 9 to 14, wherein the composition is one or more selected from decanediol, polyethylene glycol, caprylyl glycol, and derivatives or salts thereof. The external composition for skin according to any one of claims 9 to 15, wherein the (B) contains a glycol compound that is 1,2-diol. The surfactant is polyethylene glycol-40 hydrogenated castor oil, polyethylene glycol-50 hydrogenated castor oil, polyethylene glycol-60 hydrogenated castor oil, polyethylene glycol-80 hydrogenated castor oil, polyethylene glycol-100 hydrogenated castor oil. , Polyethylene glycol-25 stearate, polyethylene glycol-40 stearate, polyethylene glycol stearate 45, polyethylene glycol stearate 55, polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (4P.O.), Polyoxyethylene polyoxypropylene cetyl ether (20E.O.) (8PO), polyoxyethylene (21) lauryl ether, polyoxyethylene (25) lauryl ether, polyoxy Tylene (10) cetyl ether, polyoxyethylene (15) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, polyoxyethylene (30) cetyl Ether, polyoxyethylene (40) cetyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (10) oleyl ether, polyoxyethylene (15) oleyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (50) Oleyl ether, polyoxyethylene (20) behenyl ether, polyoxyethylene (30) behenyl ether, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate It is at least one selected from 80, the skin external composition according to any of claims 9-16. The organic solvent having a cyclic structure is at least one selected from N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, γ-butyrolactone, γ-butyrolactam, dimethylisosorbide, and sulfolane. The external composition for skin according to any one of claims 9 to 17. The organic acid and derivatives thereof are lactic acid, methyl lactate, ethyl lactate, propyl lactate, isopropyl lactate, butyl lactate, acetic acid, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, citric acid, tartaric acid, malic acid, 19. One or more selected from succinic acid, glycolic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, ε-aminocaproic acid, glutamic acid, and aminoethylsulfonic acid. The composition for external application to skin. The external composition for skin according to any one of claims 9 to 19, wherein the (B) comprises two or more glycol compounds. The hydroxyalkyl urea is methyl urea, 1-hydroxyethyl urea, 2-hydroxyethyl urea, 1-hydroxypropyl urea, 2-hydroxypropyl urea, 3-hydroxypropyl urea, 1-hydroxybutyl urea, 2-hydroxybutyl urea. 3-hydroxybutylurea, 4-hydroxybutylurea, 1-hydroxy-sec-butylurea, 2-hydroxy-sec-butylurea, 3-hydroxy-sec-butylurea, 2-hydroxy-t-butylurea, hydroxy One or more selected from pentylurea, hydroxyhexylurea, hydroxyheptylurea, hydroxyoctylurea, dihydroxyethylurea, dihydroxypropylurea, dihydroxybutylurea, and derivatives or salts thereof Skin external composition according to any of claims 1-5 and 9-20. The external composition for skin according to any one of claims 1 to 21, which is a water-soluble preparation. The external composition for skin according to any one of claims 1 to 22, which is an O / W type composition. The external composition for skin according to any one of claims 1 to 23, which is an aqueous gel composition. The external composition for skin according to any one of claims 22 to 24, wherein the aqueous solvent is water and / or an alcohol solvent. The external composition for skin according to any one of claims 22 to 25, wherein the alcohol content in the composition is 30% by weight or less.

Images