JP2021123532A - Topical skin composition - Google Patents

Abstract

To provide a topical skin composition that exhibits excellent permeability and has reduced skin irritation and suppressed precipitation at high temperatures.SOLUTION: A topical skin composition is prepared that contains (A) nicotinamide; (B) at least one selected from the group consisting of C5-10 alkanediol, propanediol, diglycerol, and hydroxyalkyl urea; and (C) glycyrrhizinic acid, glycyrrhizinate, or amphiphilic compound.SELECTED DRAWING: None

Description

The present invention relates to a composition for external use on the skin. More specifically, the present invention relates to an external composition for skin containing a nicotinic acid amide.

Nicotinamide is one of the vitamins, and has been used as a component for promoting blood circulation, anti-inflammatory, ceramide synthesis, etc. in the skin care field, and further for whitening, anti-wrinkle, and anti-aging. It is also known to have an effect.

For example, Patent Document 1 proposes a whitening agent containing at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as an active ingredient.

Further, Patent Document 2 is characterized by containing (a) a nicotinic acid amide and (b) one or more selected from the group consisting of urea and an α-hydroxycarboxylic acid compound having 2 to 28 carbon atoms. Skin anti-aging cosmetics have been proposed.

Japanese Unexamined Patent Publication No. 2004-217629 Japanese Unexamined Patent Publication No. 10-130135

Nicotinic acid amide is thus a useful ingredient, and it is desirable to enhance its penetration into the skin during use. On the other hand, pursuing the permeability of active ingredients such as nicotinic acid amide raises the issue of irritation and cell damage. Furthermore, nicotinic acid amide is known to have a problem of irritation, and in a nicotinic acid amide-containing preparation, it promotes penetration to enhance its effectiveness and is gentle on the skin (low irritation, low cytotoxicity, etc.). It is difficult to achieve both.

The present inventors prepare a composition for external use on the skin, which is a composition containing a nicotinic acid amide and which can achieve both of these characteristics while maintaining a balance between promotion of skin permeability of nicotinic acid amide and suppression of skin irritation. I succeeded in doing so. However, it has been further found that such a composition may precipitate over time due to the evaporation of water due to the high concentration of nicotinic acid amide.

Therefore, in the present invention, it is a composition for external use on the skin that can both promote penetration and suppress skin irritation, and even if it contains a high concentration of nicotinic acid amide, precipitation over time due to water evaporation is suppressed. It is an object of the present invention to provide a composition for external use on the skin.

As a result of diligent studies to solve the above problems, the present inventors have combined nicotinic acid amide with a specific alcandiol; and glycyrrhizinic acid or a salt thereof, or a nicotinic acid amide. We have found that it can promote skin permeability, suppress skin irritation, and suppress precipitation over time, and have completed the present invention.

（式中、
Ｚは、水素原子、又は、炭素数１〜３０のヒドロキシ化合物からｎ個のヒドロキシ基を除去することによって得られる残基を意味し；
ＡＯは、３〜４個の炭素原子を有するオキシアルキレン基を意味し；
ＥＯは、オキシエチレン基を意味し；
ＢＯは、４個の炭素原子を有するオキシアルキレン基を意味し；
ｎは、１〜９を意味し；
ａ，ｂ及びｃは、それぞれＡＯ、ＥＯ、ＢＯの平均付加モル数を意味し、独立して０〜２００である。但し、ａ、ｂ及びｃが全て０になることはない。また、ｎが２以上の時、複数のａ、ｂ及びｃはそれぞれ同一でも異なってもよい。Ｚが水素原子の時は、ｎは１である。
なお、ＡＯ及びＥＯは、ランダムに又はブロックの形態で付加されていてよい。）。
項２．
前記（Ｂ）成分が、１，２−ペンタンジオール、１，２−ヘキサンジオール、ジグリセリン、及び１，３−プロパンジオールからなる群より選択される１種以上であり、
前記（Ｃ）成分が、グリチルリチン酸、グリチルリチン酸の塩、及び一般式（Ｉ）で表される化合物、ホスホリルコリン含有重合体、（エイコサン二酸／テトラデカン二酸）ポリグリセリル−１０、及びシクロヘキサンジカルボン酸ビスエトキシジグリコールからなる群より選択される１種である、項１に記載の皮膚外用組成物。
項３．
前記（Ｂ）成分が、１，２−ペンタンジオール及び１，３−プロパンジオールからなる群より選択される１種以上であり、
前記（Ｃ）成分が、グリチルリチン酸、グリチルリチン酸の塩、及びホスホリルコリン含有重合体からなる群より選択される１種である、項２に記載の皮膚外用組成物。
項４．
前記（Ａ）成分の含有量が、３質量％以上である、項１〜３に記載の皮膚外用組成物。
項５．
項１〜４に記載の皮膚外用組成物であって、パラオキシ安息香酸エステルの総含有量が、０．１質量％以下である、皮膚外用組成物。 That is, the present invention provides the following external composition for skin.
Item 1.
(A) Nicotinic acid amide;
(B) At least one selected from the group consisting of alkanediols having 5 to 10 carbon atoms, propanediols, diglycerins, and hydroxyalkylureas; and (C) glycyrrhizic acid, salts of glycyrrhizic acid, and amphoteric compounds. An external composition for skin containing at least one selected from the group consisting of
A composition for external use on the skin, wherein the amphipathic compound is one or more selected from the group consisting of a compound represented by the following general formula (I), a phosphorylcholine-containing polymer, and a divalent carboxylic acid ester.

(During the ceremony,
Z means a residue obtained by removing n hydroxy groups from a hydrogen atom or a hydroxy compound having 1 to 30 carbon atoms;
AO means an oxyalkylene group having 3-4 carbon atoms;
EO means oxyethylene group;
BO means an oxyalkylene group having 4 carbon atoms;
n means 1-9;
a, b and c mean the average number of moles of AO, EO and BO, respectively, and are 0 to 200 independently. However, a, b and c are not all 0. Further, when n is 2 or more, the plurality of a, b and c may be the same or different. When Z is a hydrogen atom, n is 1.
AO and EO may be added randomly or in the form of blocks. ).
Item 2.
The component (B) is at least one selected from the group consisting of 1,2-pentanediol, 1,2-hexanediol, diglycerin, and 1,3-propanediol.
The component (C) is glycyrrhizinic acid, a salt of glycyrrhizinic acid, a compound represented by the general formula (I), a phosphorylcholine-containing polymer, polyglyceryl-10 (eicosane diic acid / tetradecanedioic acid), and biscyclohexanedicarboxylic acid. Item 2. The external composition for skin according to Item 1, which is one selected from the group consisting of ethoxydiglycol.
Item 3.
The component (B) is at least one selected from the group consisting of 1,2-pentanediol and 1,3-propanediol.
Item 2. The external composition for skin according to Item 2, wherein the component (C) is one selected from the group consisting of glycyrrhizic acid, a salt of glycyrrhizic acid, and a phosphorylcholine-containing polymer.
Item 4.
Item 3. The external composition for skin according to Item 1 to 3, wherein the content of the component (A) is 3% by mass or more.
Item 5.
Items 1 to 4 for external use on the skin, wherein the total content of the paraoxybenzoic acid ester is 0.1% by mass or less.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition for external use on the skin, in which the skin permeability of nicotinic acid amide is promoted, skin irritation is suppressed, and precipitation over time is suppressed.

In the present specification, the unit of content "mass%" is synonymous with "g / 100g".

The external composition for skin of the present invention is
(A) Nicotinic acid amide;
(B) At least one selected from the group consisting of alkanediols having 5 to 10 carbon atoms, propanediols, diglycerins, and hydroxyalkylureas; and (C) glycyrrhizic acid, salts of glycyrrhizic acid, and amphoteric compounds. An external composition for skin containing at least one selected from the group consisting of.

[(A) Nicotinic acid amide]
The nicotinic acid amide contained in the external composition for skin of the present invention is _{an amide compound of nicotinic acid (vitamin B 3} / niacin) and is a water-soluble vitamin. The nicotinic acid amide may be an extract from a natural product or a product synthesized by a known method. Specifically, those listed in the 17th revised Japanese Pharmacopoeia can be used. It is known to have a blood circulation promoting effect, a rough skin improving effect, a melanin production suppressing effect, and a whitening effect.

In the external composition for skin of the present invention, the content of the component (A) with respect to the total amount of the composition is appropriately set depending on the balance with other components. The content of the component (A) is preferably 3% by mass or more, preferably 4% by mass or more, from the viewpoint of sufficiently imparting effectiveness such as whitening and anti-aging to the total amount of the composition. More preferably, it may be 5% by mass or more. The content of the component (A) is preferably 20% by mass or less, more preferably 15% by mass or less, still more preferably 10% by mass or less, and particularly preferably 8% by mass, based on the total amount of the composition. % Or less. The content of the component (A) is preferably 3% by mass to 20% by mass, more preferably 3% by mass to 15% by mass, and further preferably 3% by mass to 10% by mass with respect to the total amount of the composition. It is even more preferably 4% by mass to 8% by mass.

[(B) At least one selected from the group consisting of alkanediol, propanediol, diglycerin, and hydroxyalkylurea having 5 to 10 carbon atoms]
The component (B) contained in the external composition for skin of the present invention is a compound usually used as a component for external preparations for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics.

The component (B) is at least one selected from the group consisting of alkanediol, propanediol, diglycerin, and hydroxyethylurea having 5 to 10 carbon atoms from the viewpoint of exerting the effect of the present invention. From the viewpoint of remarkably exerting the effect of the present invention, the component (B) contains 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,3-propanediol, diglycerin, and hydroxy. At least one selected from the group consisting of ethylurea is preferable, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,3-propanediol, or diglycerin is more preferable. 1,2-Pentanediol, 1,3-propanediol, or diglycerin is more preferred, and 1,2-pentanediol, or 1,3-propanediol is particularly preferred. The commercially available products are not particularly limited, but are Zemea Select Propanediol, HYDROLLITE-5, HYDROLLITE-5 Green (manufactured by Simrise Co., Ltd.), KMO-6 (manufactured by Osaka Organic Chemical Industry Co., Ltd.), Microcare Emolinent PTGJ, and Microcare. Emorient HXD (manufactured by THOR), diol PD, diol PD-V (manufactured by Higher Alcohol Industry Co., Ltd.), diglycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.), Uniglycer 2 (manufactured by Nichiyu Co., Ltd.), Hydrovance (Axo) Nobel Co., Ltd.) etc. can be used.

Among the components (B), the alkanediol having 5 to 10 carbon atoms has a preferably 5 to 10 carbon atoms, more preferably 5 to 8 carbon atoms, and further preferably 5 to 5 carbon atoms from the viewpoint of significantly exerting the effect of the present invention. 6 alkanediol. As such an alkanediol, for example, 1,2-pentanediol, 1,2-hexanediol, or 1,2-octanediol is preferable, and 1,2-pentanediol or 1,2-hexanediol is more preferable. , 1,2-Pentanediol is more preferred.

Among the components (B), hydroxyalkyl urea refers to a compound in which at least one hydrogen atom of urea (urea) is substituted with a hydroxyalkyl group. From the viewpoint of remarkably exerting the effect of the present invention, specific examples of the hydroxyalkyl group include a hydroxyethyl group, a hydroxypropyl group, a hydroxybutyl group, a dihydroxybutyl group, a hydroxypentyl group, and a hydroxyhexyl group. Can be mentioned. Of these, a hydroxyethyl group is preferable.

More specifically, as hydroxyalkyl urea, N- (2-hydroxyethyl) urea, N- (2-hydroxypropyl) urea, N- (3-hydroxypropyl) urea, N- (2,3-dihydroxypropyl) ) Urea, N- (2-hydroxybutyl) urea, N- (3-hydroxybutyl) urea, N, N'-bis (2-hydroxypropyl) -N'-(2-hydroxyethyl) urea and the like. Will be done.
The number of hydroxyalkyl groups in the hydroxyalkyl urea is preferably 1 to 3, more preferably 1 to 2, and even more preferably 1 (monohydroxyalkyl urea). Of these, hydroxyethylurea is preferable.

In the present invention, one type of component (B) may be used alone, or two or more types may be used in any combination.

In the external composition for skin of the present invention, the total content of the component (B) with respect to the total amount of the composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably. 0.5% by mass or more, more preferably 1% by mass or more,
Particularly preferably, it is 1.5% by mass or more. The content of the component (B) is preferably 30% by mass or less, more preferably 25% by mass or less, still more preferably 20% by mass or less, still more preferably 15% by mass, based on the total amount of the composition. % Or less, particularly preferably 10% by mass or less. The total content of the component (B) is preferably 0.01 to 30% by mass, more preferably 0.1 to 25% by mass, still more preferably 0.5 to 20% by mass, and even more preferably 1 to 1. It is 15% by mass, particularly preferably 1.5 to 15% by mass.

In the external composition for skin of the present invention, the ratio of the total content of the component (B) to the component (A) is not particularly limited, but the component (B) is preferably used with respect to 1 part by mass of the component (A). 0.001 to 30 parts by mass, more preferably 0.02 to 10 parts by mass, still more preferably 0.01 to 5 parts by mass, even more preferably 0.1 to 5 parts by mass, particularly preferably 0.1. ~ 4 parts by mass.

[(C) component]
The component (C) contained in the external composition for skin of the present invention is at least one selected from the group consisting of glycyrrhizic acid, a salt of glycyrrhizic acid, and an amphipathic compound.

((C-1) Glycyrrhizic acid or salt of glycyrrhizic acid)
As the glycyrrhizic acid or the salt of glycyrrhizic acid used in the present invention, a compound usually used as a component of an external preparation for skin in the fields of pharmaceuticals, quasi-drugs or cosmetics can be used.

In the present invention, the salt of glycyrrhizinic acid is a pharmaceutically acceptable salt of glycyrrhizinic acid, and is not limited, for example, a salt with an organic base (for example, a tertiary amine salt, an ammonium salt, etc.). , Or salts with inorganic bases (eg, inorganic salts such as hydrochlorides, sulfates, phosphates; alkali metal salts such as sodium salts, potassium salts, dipotassium salts, etc.) and the like. Among them, preferable salts are monoammonium salt, sodium salt, potassium salt and dipotassium salt, more preferable salt is monoammonium salt or dipotassium salt, and particularly preferable salt is dipotassium salt.

These can be synthesized, or commercially available products can be used as they are. Examples of commercially available products include, but are not limited to, glycyrrhizic acid, dipotassium glycyrrhizinate, dipotassium glycyrrhizinate, and monoammonium glycyrrhizinate manufactured by Maruzen Pharmaceuticals Co., Ltd. or Alps Pharmaceutical Co., Ltd.

These glycyrrhizic acid or salts of glycyrrhizic acid can be used alone or in combination of two or more.

In the external composition for skin of the present invention, the total content of the component (C-1) is not particularly limited and is appropriately set according to the type of the component (B), the type of other compounding components, and the like. From the viewpoint of significantly exerting the effect of the present invention, it is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, still more preferably 0.005% by mass or more, and further, based on the total amount of the composition. More preferably, it is 0.01% by mass or more, and most preferably 0.05% by mass or more.
The total content of the component (C-1) is preferably 5% by mass or less, more preferably 2% by mass or less, still more preferably 1% by mass or less, still more preferably 1% by mass or less, based on the total amount of the composition. It is 0.5% by mass or less, most preferably 0.2% by mass or less.

In the external composition for skin of the present invention, the total content of (C-1) glycyrrhizinic acid or the salt of glycyrrhizinic acid with respect to the total amount of the composition is preferably 0.0001 to 5% by mass, more preferably 0.001 to 0.001. It is 2% by mass, more preferably 0.005 to 1% by mass, even more preferably 0.01 to 0.5% by mass, and particularly preferably 0.05 to 0.2% by mass.

In the external composition for skin of the present invention, the ratio of the total content of (C-1) glycyrrhizinic acid or the salt of glycyrrhizinic acid to the component (A) is not particularly limited, but is based on 1 part by mass of the component (A). , (C-1) Glycyrrhizic acid, or a salt of glycyrrhizic acid, preferably 0.000005 to 1.7 parts by mass, more preferably 0.0001 to 0.67 parts by mass, still more preferably 0.001 to 0. It is 4 parts by mass, more preferably 0.002 to 0.1 parts by mass, and particularly preferably 0.002 to 0.02 parts by mass.

((C-2) amphipathic compound)
The amphipathic compound contained in the external composition for skin as the component (C-2) of the present invention has both a hydrophilic group and a hydrophobic group (lipophilic group) in one molecule, and as a result, an aqueous phase and an oil. Refers to all compounds that have an affinity for any of the phases (organic phases).

（式中、
Ｚは、水素原子、又は、炭素数１〜３０のヒドロキシ化合物からｎ個のヒドロキシ基を除去することによって得られる残基を意味し；
ＡＯは、３〜４個の炭素原子を有するオキシアルキレン基を意味し；
ＥＯは、オキシエチレン基を意味し；
ＢＯは、４個の炭素原子を有するオキシアルキレン基を意味し；
ｎは、１〜９を意味し；
ａ，ｂ及びｃは、それぞれＡＯ、ＥＯ、ＢＯの平均付加モル数を意味し、独立して０〜２００である。但し、ａ、ｂ及びｃが全て０になることはない。また、ｎが２以上の時、複数のａ、ｂ及びｃはそれぞれ同一でも異なってもよい。Ｚが水素原子の時は、ｎは１である。
なお、ＡＯ及びＥＯは、ランダムに又はブロックの形態で付加されていてよい。）。本発明の（Ｃ−２）成分としては、これらの化合物のいずれか単独、又は２種以上を組み合わせて用いることができる。（Ｃ−２）成分を、（Ａ）成分及び（Ｂ）成分とともに配合させることにより、高濃度のニコチン酸アミドを配合した場合であっても、析出が抑制された皮膚外用組成物を提供することが可能となる。 Such an amphipathic compound is one or more selected from the group consisting of a compound represented by the following general formula (I), a phosphorylcholine-containing polymer, and a divalent carboxylic acid ester.

(During the ceremony,
Z means a residue obtained by removing n hydroxy groups from a hydrogen atom or a hydroxy compound having 1 to 30 carbon atoms;
AO means an oxyalkylene group having 3-4 carbon atoms;
EO means oxyethylene group;
BO means an oxyalkylene group having 4 carbon atoms;
n means 1-9;
a, b and c mean the average number of moles of AO, EO and BO, respectively, and are 0 to 200 independently. However, a, b and c are not all 0. Further, when n is 2 or more, the plurality of a, b and c may be the same or different. When Z is a hydrogen atom, n is 1.
AO and EO may be added randomly or in the form of blocks. ). As the component (C-2) of the present invention, any one of these compounds alone or a combination of two or more thereof can be used. By blending the component (C-2) together with the components (A) and (B), a composition for external use on the skin in which precipitation is suppressed even when a high concentration of nicotinic acid amide is blended is provided. It becomes possible.

From the viewpoint of providing a good composition for external use on the skin, the alkylene oxide derivative is preferably a compound represented by the following general formula (II).

（式中、
Ｚは、水素原子、又は、炭素数１〜３０のヒドロキシ化合物からｎ個のヒドロキシ基を除去することによって得られる残基を意味し；
ＡＯは、３〜４個の炭素原子を有するオキシアルキレン基を意味し；
ＥＯは、オキシエチレン基を意味し；
ｎは、１〜９を意味し；
ａ及びｂは、それぞれＡＯ、ＥＯの平均付加モル数を意味し、独立して０〜２００である。但し、ａ及びｂが全て０になることはない。また、ｎが２以上の時、複数のａ、ｂはそれぞれ同一でも異なってもよい。Ｚが水素原子の時はｎは１である。
なお、ＡＯ及びＥＯは、ランダムに又はブロックの形態で付加されていてよい。）

(During the ceremony,
Z means a residue obtained by removing n hydroxy groups from a hydrogen atom or a hydroxy compound having 1 to 30 carbon atoms;
AO means an oxyalkylene group having 3-4 carbon atoms;
EO means oxyethylene group;
n means 1-9;
a and b mean the average number of moles of AO and EO added, respectively, and are independently 0 to 200. However, a and b are not all 0. Further, when n is 2 or more, the plurality of a and b may be the same or different. When Z is a hydrogen atom, n is 1.
AO and EO may be added randomly or in the form of blocks. )

The alkylene oxide derivative used in the present invention is a polymer of a specific alkylene glycol (when Z is a hydrogen atom) or a specific hydroxy compound (corresponding to Z) and a specific alkylene oxide group (general formula (I)). And (II) a compound obtained by adding (corresponding to the portion excluding Z) (when Z is a group obtained by removing n hydroxy groups from a hydroxy compound having 1 to 30 carbon atoms).

In the alkylene oxide derivative used in the present invention, from the viewpoint of providing a good composition for external use on the skin, AO is an oxyalkylene group having 3 to 4 carbon atoms, and examples thereof include an oxypropylene group and an oxybutylene group (oxyn). -Butylene group, oxyisobutylene group, oxyt-butylene group), oxytrimethylene group, oxytetramethylene group and the like. The AO is preferably an oxypropylene group, an oxybutylene group, and more preferably an oxypropylene group.

In the alkylene oxide derivative used in the present invention, BO is an oxyalkylene group having 4 carbon atoms, and examples thereof include an oxybutylene group (oxyn-butylene group, oxyisobutylene group, oxyt-butylene group) and oxytetramethylene. The group etc. can be mentioned. It is preferably an oxybutylene group.

In the alkylene oxide derivative used in the present invention, a, b, and c are independently 0 to 200, respectively. A, b, and c are independently, preferably 1 to 200, more preferably 2 to 150, still more preferably 2 to 100, and particularly preferably 2 to 70.

In the chemical formula (I), a + b + c, which is the total number of each monomer unit of AO, EO, and BO, is preferably 3 or more, more preferably 5 or more, still more preferably 10 or more, from the viewpoint of significantly exerting the effect of the present invention. Is. Further, a + b + c is preferably 450 or less, more preferably 350 or less, still more preferably 300 or less, and particularly preferably 250 or less, from the viewpoint of remarkably exerting the effect of the present invention.

In the chemical formula (II), a + b, which is the total number of each monomer unit of AO and EO, is preferably 3 or more, more preferably 5 or more, still more preferably 10 or more from the viewpoint of significantly exerting the effect of the present invention. .. Further, a + b is preferably 400 or less, more preferably 300 or less, still more preferably 250 or less, and particularly preferably 200 or less, from the viewpoint of remarkably exerting the effect of the present invention.

In the formulas (I) and (II), from the viewpoint of providing a composition for external use on the skin having good properties, Z is a hydrogen atom or an alkyl monoalcohol having 4 to 24 carbon atoms, glycerin, or tri. Obtained by removing n hydroxy groups from methylolpropane, erythritol, pentaerythritol, alkyl glucosides with 1 to 24 carbon atoms, diglycerin, xylitol, dipentaerythritol, sorbitol, inositol, sucrose, trehalose, or martitol. It is preferably a residue to be added, that is, a residue derived from these alcohol compounds, which is a hydrogen atom or an alkyl monoalcohol having 4 to 24 carbon atoms, glycerin (hydroxyl to which an alkylene oxide group can be added). 3 groups), pentaerythritol (4 hydroxy groups to which an alkylene oxide group can be added), alkyl glucoside having 1 to 24 carbon atoms (4 hydroxy groups to which an alkylene oxide group can be added), diglycerin (alkylene) More preferably, it is a residue obtained by removing n hydroxy groups from sorbitol (6 hydroxy groups to which an alkylene oxide group can be added) or sorbitol (6 hydroxy groups to which an alkylene oxide group can be added). A hydrogen atom or a residue obtained by removing n hydroxy groups from an alkyl monoalcohol having 4 to 24 carbon atoms, glycerin, an alkyl glucoside having 1 to 24 carbon atoms, diglycerin, or sorbitol. More preferably, it is a hydrogen atom or is obtained by removing n hydroxy groups from an alkyl monoalcohol having 4 to 24 carbon atoms, glycerin, an alkyl glucoside having 1 to 24 carbon atoms, or diglycerin. It is more preferably a residue obtained by removing n hydroxy groups from an alkyl monoalcohol having 4 to 24 carbon atoms, glycerin, an alkyl glucoside having 1 to 5 carbon atoms, or diglycerin. It is more preferable to have.

In the case of the alkyl monoalcohol in which Z has 4 to 24 carbon atoms in the chemical formula (I) or (II), butyl alcohol, decyltetradecyl alcohol, cetanol, and stearyl alcohol are among others from the viewpoint of remarkably exerting the effect of the present invention. Butyl alcohol and decyltetradecyl alcohol are particularly preferred.

In the chemical formula (I) or (II), when Z is an alkyl glucoside, the alkyl glucoside having 1 to 24 carbon atoms is preferable, and the alkyl glucoside having 1 to 16 carbon atoms is preferable from the viewpoint of remarkably exerting the effect of the present invention. More preferably, an alkyl glucoside having 1 to 10 carbon atoms is even more preferable, and an alkyl glucoside having 1 to 6 carbon atoms is particularly preferable.

Such an alkylene oxide derivative can be synthesized by a known method. For example, it is obtained by addition-polymerizing ethylene oxide and an alkylene oxide having 3 to 4 carbon atoms to a hydroxy compound having 1 to 30 carbon atoms, and then reacting the alkylene oxide with 4 carbon atoms. At the stage of addition polymerization of ethylene oxide and alkylene oxide having 3 to 4 carbon atoms to a hydroxy compound having 1 to 30 carbon atoms, ethylene oxide and alkylene oxide may be randomly polymerized or block polymerized. May be good. An alkali catalyst, a phase transfer catalyst, a Lewis acid catalyst, or the like can be used for the addition reaction. Generally, it is preferable to use an alkaline catalyst such as potassium hydroxide.

The molecular weight of such an alkylene oxide derivative is not limited as long as the effect of the present invention is exhibited, but is preferably 200 or more, more preferably 300 or more, from the viewpoint of significantly exerting the effect of the present invention. More preferably, it is 400 or more.

The properties of the alkylene oxide derivative are not limited as long as the effects of the present invention are exhibited, but in the above formulas (I) and (II), from the viewpoint of significantly exhibiting the effects of the present invention, it is preferably in a semi-solid state at 25 ° C. It is preferable that the component is in the form of (including paste) to liquid.

In addition, such alkylene oxide derivatives include, for example, polyoxyalkylene glyceryl ether, polyoxyalkylene alkyl glucoside, polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene oxybutylene alkyl ether, and the like. Polyoxyalkylene sorbit, polyoxyalkylene erythritol ether, polyoxyalkylene pentaerythritol ether, polyoxyalkylene diglyceryl ether, polyoxyalkylene trimethylol propane, polyoxypropylene glycol, polyoxyethylene polyoxypropylene glycol, polyoxyalkylene xylitol, Examples thereof include polyoxyalkylene dipentaerythritol, polyoxyalkylene inositol, polyoxyalkylene sucrose ether, polyoxyalkylene trehalose ether, and polyoxyalkylene multitoll ether.

Among them, the alkylene oxide derivatives are polyoxyethylene glyceryl ether, polyoxypropylene glyceryl ether, polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether, and polyoxybutylene polyoxyethylene polyoxypropylene alkyl. Glucoside, polyoxyethylene polyoxypropylene alkyl glucoside, polyoxyethylene alkyl glucoside, polyoxypropylene alkyl glucoside, polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxypropylene sorbit, polyoxyethylene sorbit, polyoxy Ethylene polyoxypropylene sorbit, polyoxypropylene erythritol ether, polyoxyethylene erythritol ether, polyoxyethylene pentaerythritol ether, polyoxyethylene polyoxypropylene erythritol ether, polyoxypropylene pentaerythritol ether, polyoxyethylene polyoxypropylene pentaerythritol ether , Polyoxybutylene polyoxyethylene pentaerythritol ether, polyoxyethylene diglyceryl ether, polyoxypropylene diglyceryl ether, polyoxyethylene polyoxypropylene diglyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene diglyceryl ether, polyoxy Ethylene Trimethylol Propane, Polyoxypropylene Trimethylol Propane, Polyoxyethylene Polyoxypropylene Trimethylol Propane, Polyoxypropylene Glycol, Polyoxyethylene Polyoxypropylene Glycol, Polyoxybutylene Polyoxyethylene Polyoxypropylene Glycol, Polyoxyethylene Xylitol , Polyoxypropylene alkylenexylitol, polyoxyethylene polyoxypropylene xylitol, polyoxyethylene polyoxypropylene dipentaerythritol, polyoxyethylene dipentaerythritol, polyoxypropiresipentaerythritol, polyoxyethylene inositol, polyoxypropylene inositol, poly Oxyethylene polyoxypropylene inositol, polyoxyethylene sucrose ether, polyo Xypropylene sucrose ether, polyoxyethylene polyoxypropylene sucrose ether, polyoxyethylene trehalose ether, polyoxypropylene trehalose ether, polyoxyethylene polyoxypropylene trehalose ether, polyoxyethylene multoll ether, polyoxypropylene multoll ether, and One or more selected from the group consisting of polyoxyethylene polyoxypropylene maltitol ether is preferable.
Polyoxyethylene glyceryl ether, polyoxypropylene glyceryl ether, polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene alkyl glucoside, polyoxyethylene alkyl glucoside , Polyoxypropylene alkyl glucoside, polyoxypropylene diglyceryl ether, polyoxyethylene diglyceryl ether, polyoxypropylene alkyl ether, and one or more selected from the group consisting of polyoxyethylene polyoxypropylene alkyl ether. Preferably, polyoxyethylene glyceryl ether, polyoxypropylene glyceryl ether, polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene alkyl glucoside, polyoxyethylene Group consisting of methyl glucoside, polyoxypropylene methyl glucoside, polyoxypropylene diglyceryl ether, polyoxyethylene diglyceryl ether, polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene decyltetradecyl ether and polyoxyethylene polyoxypropylene butyl ether One or more selected from the above is even more preferable.

These can be synthesized, or commercially available products can be used as they are. Commercially available products include, but are not limited to, Unilube 50MB-26 (polyoxyethylene polyoxypropylene butyl ether (17EO) (17PO)), Unilube 50MB-168 (polyoxyethylene polyoxypropylene butyl ether (37E)). O.) (38PO)), Unilube 50MB-11 (Polyoxyethylene polyoxypropylene butyl ether (9EO) (10PO)), Unisafe 10P-8 (Polyoxyethylene polyoxypropylene cetyl) Ether (10EO) (8PO)), Unilube MT-630B (polyoxyethylene polyoxypropylene decyltetradecyl ether (30EO) (6PO)), Solbuel GS-01 (poly) Oxyethylene polyoxypropylene decyltetradecyl ether (24EO) (13PO)), Unilube MS-70K (polyoxypropylene stearyl ether (15PO)), Uniol HS-1600D (polyoxyalkylene sorbit) ), Pronon # 208 (polyoxyethylene polyoxypropylene glycol (150EO) (35PO)), pronon # 124P (polyoxyethylene (20) polyoxypropylene (20) glycol), Uniol D-2000 (Polypropylene glycol), Macbiobride MG-10E (polyoxyethylene methyl glucoside (10EO)), Macbiobride MG-20E (polyoxyethylene methyl glucoside (20EO)), Macbiobride MG- 10P (Polyoxypropylene methyl glucoside (10PO), Macbiobride MG-20P (Polyoxypropylene methyl glucoside (20PO)), Wilbride MG2070 (Polyoxybutylene polyoxyethylene polyoxypropylene methyl glucoside) , Unilube 5TP-300KB (Polyoxyethylene Polyoxypropylene Pentaerythritol Ether (5EO) (65P.O.)); Unilube 50TG-32 (Polyoxyethylene Polyoxypropylene Glyceryl Ether (24EO) (24P)) O.)), Wilbride S-753 (polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether (3BO) (8EO) (5PO)), Uniox G-1200 (polyoxy) (Ethylene glycerin), Unilube DGP-700, Unilube DGP-950 (Polyoxypropylene diglyceryl ether) (above, manufactured by Nichiyu Co., Ltd.); SY-DP14, SY-DP9 (Polyoxypropylene diglyceryl ether) (above, Sakamoto) Yakuhin Kogyo Co., Ltd.; New Pole GP-1000 (PPG-16 glyceryl ether), New Pole SP-750 (polyoxyalkylene sorbitol ether), New Pole PE-68 (polyoxyethylene polyoxypropylene glycol (160E.). O. ) (30PO)), Nieuport PE-78 (polyoxyethylene polyoxypropylene glycol (150EO) (35PO)), Nieuport GEP-2800 (polyoxyethylene polyoxypropylene glyceryl ether) (24EO) (24PO)) (above, manufactured by Sanyo Kasei Co., Ltd.); Emargen PP-290 (polyoxyethylene polyoxypropylene glycol (160EO) (30PO), Kao shares NIKKOL SG-G2424 (polyoxyethylene polyoxypropylene glyceryl ether (24EO) (24PO), NIKKOL SG-DTD630 (polyoxyethylene polyoxypropylene decyltetradecyl ether) (30EO. ) (6PO), NIKKOL SG-DTD620 (polyoxyethylene polyoxypropylene decyltetradecyl ether (20EO) (6PO)), NIKKOL PEN-4612 (polyoxyethylene polyoxypropylene decyltetra) Decyl ether (12EO) (6PO)) (above, manufactured by Nikko Chemicals); GLUCAM P-10 (polyoxypropylene methyl glucoside (10PO)), GLUCAM P-20 (polyoxypropylene methyl). Glucoside (20PO)) GLUCAM E-10 (polyoxyethylene methyl glucoside (10PO)) and GLUCAM E-20 (polyoxyethylene methyl glucoside (20PO)) (above, Lubrizol) It is preferable that the mixture is one or more selected from the group consisting of (manufactured by), and is preferably one or more of unilub 50MB-26, unilub 50MB-168, macbiobride MG-10E, macbiobride MG-20E, macbiobride MG-10P, and macbio. Bride MG-20P, Wilbride MG2070, Wilbride S-753, Unilube 5TP-300KB, Unilube 50TG-32, Uniox G-1200, Unilube DGP-700, Unilube DGP-950, Nieuport GEP-2800, NIKKOL SG- G2424, GLUCAM P-10, GLUCAM P-20, GLUCAM E-10, NIKKOL PEN-4612, NIKKOL SG-DTD620, NIKKOL SG-DTD630,
It is preferably one or more selected from the group consisting of Unilube MT-630B, Solbure GS-01 and GLUCAM E-20.

In the present invention, one type of alkylene oxide derivative may be used alone, or two or more types may be used in any combination.

The phosphorylcholine-containing polymer refers to all polymers containing an organic compound containing phosphorylcholine as a monomer. Although not particularly limited, a 2-metacloyloxyphosphorylcholine-containing polymer, which is a polymer obtained by polymerizing a monomer containing 2-methacryloyloxyethyl phosphorylcholine, is particularly preferable from the viewpoint of significantly exerting the effect of the present invention. Among them, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer (polyquaternium-51), 2-methacryloyloxyethyl phosphorylcholine / stearyl methacrylate copolymer, 2-methacryloyloxyethyl phosphorylcholine polymer, and polymethacryloyloxyethyl phosphorylcholine. One or more selected from the group consisting of polymers is preferable, and 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer is more preferable. Commercially available products of the phosphorylcholine-containing polymer include Lipidure-PMB (2-methacryloyloxyethyl phosphorylcholine / butylmethacrylate copolymer solution, polyquaternium-51) and Lipidure-HM (polymethacryloyloxyethyl phosphorylcholine) (both are NOF Corporation). One or more selected from the group consisting of (manufactured by Co., Ltd.) is preferable, and Lipidure-PMB (2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer solution) is more preferable.

The divalent carboxylic acid ester is an ester condensed with a divalent carboxylic acid and a hydroxy group such as glycol or glycol ether, and is not particularly limited. For example, (eicosandioic acid / tetradecanedioic acid) polyglyceryl-10, cyclohexanedicarboxylic acid. Bisethoxydiglycolic acid, bis 1,4-cyclohexanedicarboxylic acid (triethylene glycol monoethyl ether), bis adipate (diethylene glycol monoethyl ether), bis adipate (triethylene glycol monoethyl ether), and diethoxy succinate Ethyl and diethylhexyl succinate are mentioned, and among them, polyglyceryl-10 (eicosandioic acid / tetradecanedioic acid), bisethoxydiglycol cyclohexanedicarboxylic acid, diethoxyethyl succinate, diethylhexyl succinate are preferable, and (eicosanedioic acid / (Tetradecanedioic acid) polyglyceryl-10 and bisethoxydiglycol cyclohexanedicarboxylic acid are more preferable, and bisethoxydiglycol cyclohexanedicarboxylic acid is even more preferable. The commercially available products are not particularly limited, but are: diethoxyethyl succinate (CRODAMOL DES), diethylhexyl succinate (CRODAMOL OSU) (all manufactured by Clauder Japan Co., Ltd.), Neosolue-Aqua, Neosolue-AquaS ((() Icosane diacid / tetradecanedioic acid) polyglyceryl-10) and Neosolue-Aquolio (bisethoxydiglycolcyclohexanedicarboxylic acid) (both manufactured by Nippon Seika Co., Ltd.) can be used.

In the external composition for skin of the present invention, the total content of the component (C-2) is not particularly limited and is appropriately set according to the type of the component (B), the type of other compounding components, and the like. From the viewpoint of significantly exerting the effect of the present invention, it is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, still more preferably 0.005% by mass, based on the total amount of the composition. As mentioned above, even more preferably, it is 0.05% by mass or more, and particularly preferably 0.1% by mass or more.
The total content of the component (C-2) is preferably 20% by mass or less, more preferably 15% by mass or less, still more preferably 12% by mass or less, still more preferably, based on the total amount of the composition. It is 10% by mass or less, most preferably 8% by mass or less.
The total content of the component (C-2) is preferably 0.0001 to 20% by mass, more preferably 0.001 to 15% by mass, still more preferably 0.005 to 12% by mass, based on the total amount of the composition. %, More preferably 0.05 to 10% by mass, and most preferably 0.1 to 8% by mass.

In the external composition for skin of the present invention, the ratio of the total content of the component (C-2) to the component (A) is not particularly limited, but the component (C-2) is contained in 1 part by mass of the component (A). It is preferably 0.00001 to 4 parts by mass, more preferably 0.00000 to 1 to 3 parts by mass, and further preferably 0.001 to 2 parts by mass.

In the external composition for skin of the present invention, the content of the alkylene oxide derivative alone with respect to the total amount of the composition is not particularly limited as long as the effects of the present invention are exhibited.
The content of the alkylene oxide derivative alone is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.5% by mass or more, based on the total amount of the composition. ..
The content of the alkylene oxide derivative alone is preferably 15% by mass or less, more preferably 10% by mass or less, still more preferably 8% by mass or less, based on the total amount of the composition.
The content of the alkylene oxide derivative alone is preferably 0.01 to 15% by mass, more preferably 0.1 to 10% by mass, and further preferably 0.% by mass, based on the total amount of the composition. It is 5 to 8% by mass, and even more preferably 0.5 to 5% by mass.

In the external composition for skin of the present invention, the content of the phosphorylcholine-containing polymer with respect to the total amount of the composition is not particularly limited as long as the effects of the present invention are exhibited.
The content of the phosphorylcholine-containing polymer is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, still more preferably 0.005% by mass or more, still more, based on the total amount of the composition. Preferably, it is 0.01% by mass or more.
The content of the phosphorylcholine-containing polymer is preferably 1% by mass or less, more preferably 0.5% by mass or less, still more preferably 0.4% by mass or less, still more preferably, based on the total amount of the composition. , 0.2% by mass or less.
The content of the phosphorylcholine-containing polymer is preferably 0.0001 to 1% by mass, more preferably 0.001 to 0.5% by mass, still more preferably 0.005 to 0, based on the total amount of the composition. It is .4% by mass, and even more preferably 0.01 to 0.2% by mass.

In the present invention, it is also preferable to combine one or more of the components (C-1) and one or more of the components (C-2) as the component (C).

Such a combination includes (C-1) component dipotassium glycyrrhizinate and (C-2) component polyoxyethylene glyceryl ether, polyoxypropylene glyceryl ether, polyoxyethylene polyoxypropylene glyceryl ether, and poly. Oxybutylene polyoxyethylene polyoxypropylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene alkyl glucoside, polyoxyethylene methyl glucoside, polyoxypropylene methyl glucoside, polyoxypropylene diglyceryl ether, polyoxyethylene diglyceryl ether, poly Oxypropylene alkyl ether, polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene polyoxypropylene butyl ether, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer solution, polymethacryloyloxyethyl phosphorylcholine, (eicosanedioic acid / tetradecane) Diacid) It is preferable to combine one or more selected from the group consisting of polyglyceryl-10, bisethoxydiglycol cyclohexanedicarboxylic acid, diethoxyethyl succinate, and diethylhexyl succinate.
Dipotassium glycyrrhizinate as a component (C-1) and polyoxyethylene glyceryl ether, polyoxypropylene glyceryl ether, polyoxyethylene polyoxypropylene glyceryl ether, and polyoxybutylene polyoxyethylene polyoxy as components (C-2). Propylene glyceryl ether, polyoxybutylene polyoxyethylene polyoxypropylene alkyl glucoside, polyoxyethylene methyl glucoside, polyoxypropylene methyl glucoside, polyoxyethylene polyoxypropylene decyltetradecyl ether, polyoxyethylene polyoxypropylene butyl ether, 2-methacryloyl Selected from the group consisting of oxyethylphosphorylcholine / butyl methacrylate copolymer solution, polyglyceryl-10 (eicosanedioic acid / tetradecanedioic acid), bisethoxydiglycol cyclohexanedicarboxylic acid, diethoxyethyl succinate, and diethylhexyl succinate 1 It is more preferable to combine seeds or two or more kinds.

[Other ingredients]
In addition to the above-mentioned essential components, the external composition for skin of the present invention has an ultraviolet protective agent, an ultraviolet absorber, a component having a DNA damage prevention and / or repair effect, in order to add other useful effects. Whitening ingredient, anti-inflammatory ingredient, refreshing agent, organic acid, anti-glycation ingredient, antibacterial ingredient, cell activating ingredient, astringent ingredient, antioxidant ingredient, anti-aging ingredient, moisturizing ingredient, polyhydric alcohol, keratin softening ingredient, vitamins , Blood circulation promoting component, sebum adsorbing component, peptide or derivative thereof, amino acid or derivative thereof and the like may be blended in one type or in combination of two or more. The respective components are not particularly limited as long as they can be used in the fields of pharmaceuticals, quasi-drugs, cosmetics, etc., and any one can be appropriately selected and used. In addition, those corresponding to the following plurality of components can be added as components having any effect among them.

However, in the external composition for skin of the present invention, the content of paraoxybenzoic acid ester (paraben) is preferably 0.1% by mass or less, more preferably 0.01% by mass or less, and 0.001% by mass or less. Even more preferred, most preferably paraben-free. Examples of the paraoxybenzoic acid ester (paraben) include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate.

Examples of the ultraviolet protective agent include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, silicic anhydride, cerium silicate, and hydrous silicic acid, and the like. Inorganic compounds are coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica and talc, compounded with resin powders such as polyamide, polyethylene, polyester, polystyrene and nylon, and silicone oils and fatty acids. Examples thereof include those treated with aluminum salts, alkyl titanates and the like. Among them, inorganic compounds such as zinc oxide, titanium oxide and iron oxide, and those obtained by coating these inorganic compounds with inorganic powder such as aluminum hydroxide, hydrous silicic acid, mica or talc or silicone oil are preferable. When the ultraviolet scattering component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.001 to 35% by mass with respect to the total amount of the external composition for skin of the present invention. It is preferably about 0.1 to 25% by mass.

The ultraviolet absorber is not limited, but is preferably a salicylic acid-based ultraviolet absorber, a silicic acid-based ultraviolet absorber, a benzoylmethane-based ultraviolet absorber, an benzoic acid ester derivative ultraviolet absorber, a triazine derivative ultraviolet absorber, and the like. It may be a benzalmalonate derivative UV absorber, an octocrylene-based UV absorber, an imidazole sulfonic acid derivative UV absorber, a benzophenone derivative UV absorber, or the like.

In the present invention, such ultraviolet absorbers include, but are not limited to, 2-ethylhexyl paramethoxysilicate, 4-tert-butyl-4'-methoxydibenzoylmethane, 2- [4- (diethylamino)-. 2-Hydroxybenzoyl] benzoic acid hexyl ester, 2-ethylhexyl dimethoxybenzidenedioxoimidazolidine propionate, 2,2'-methylenebis [6- (2H-benzotriazol-2yl) -4- (1,1,3) , 3-Tetramethylbutyl) phenol], 2,4-bis- [{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5- Triazine, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, dimethicodiethylbenzalmalonate, 2-cyano-3,3-diphenylpropa-2 -Preferably 2-ethylhexyl ester of enoic acid and 2-phenylbenzoimidazole-5-sulfonic acid, 2-ethylhexyl paramethoxysilicate, 4-tert-butyl-4'-methoxydibenzoylmethane, 2- [4 -(Diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4-bis- [{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1 , 3,5-Triazine, 2,4,6-Tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 2-phenylbenzoimidazole-5-sulfonic acid are more preferred. , 2-Ethylhexyl paramethoxysilicate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4-bis- [{4- (2-ethylhexyloxy) -2-hydroxy} -Phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine More preferable.

As the ultraviolet absorber, a commercially available product can be used, or a synthetic product can be used.

Commercially available products include, but are not limited to, Parsol EHS (manufactured by DSM Nutrition Japan), ESCAL 587 (manufactured by Ashland Japan), EusolexOS (manufactured by Merck), Parsol HMS (manufactured by DSM Nutrition Japan), Uvinul MC80 (manufactured by BASF), Parsol MCX (manufactured by DSM Nutrition Japan), Parsol 1789 (manufactured by DSM Nutrition Japan), Ubinal A Plus Granular, Soft Shade DH, Tinosorb M (manufactured by BASF), Milestab 3 / 100, Tinosorb S (manufactured by BASF), Uvasorb HEB, Ubinal T150 (manufactured by BASF), Heliosun OTZ (manufactured by O'Laughlin Industries), Parsol SLX (manufactured by DSM Nutrition Japan), Parsol 3 , Escalol 597 (Ashland Japan), Parsol HS (DSM Nutrition Japan), Eusolex232 (Merk), NeoHeliopanAP (Herman & Reimer), Ubinal M40, Escalol 567 Ashland Japan ), Ubinal MS40 (manufactured by BASF), EESORB107 (manufactured by Sipro Kasei), SEESORB100 (manufactured by Sipro Kasei), SEESORB106 (manufactured by Sipro Kasei).

In the external composition for skin of the present invention, the total content of the ultraviolet absorber is preferably 1% by mass or more, more preferably 3% by mass or more, still more preferably 6% by mass, based on the total amount of the composition. As mentioned above, it is particularly preferable that it is 7% by mass or more. The total content of the ultraviolet absorber is preferably 20% by mass or less, more preferably 15% by mass or less, still more preferably 10% by mass or less, based on the total amount of the composition. The total content of the ultraviolet absorber is preferably 1 to 20% by mass, more preferably 3 to 15% by mass, still more preferably 5 to 10% by mass, and particularly preferably 5 to 10% by mass, based on the total amount of the composition. , 7-10% by mass.

In the external composition for skin of the present invention, the ratio of the total content of the ultraviolet absorber to the component (A) is not particularly limited, but the ultraviolet absorber is preferably 0. It is 6 to 2 parts by mass, more preferably 1 to 2 parts by mass, and even more preferably 1.4 to 2 parts by mass.

Further, these UV protective agents and UV absorbers may be compounded, supported or encapsulated in another component, and the combination thereof is not particularly limited.

Ingredients that have the effect of preventing and / or repairing DNA damage include, for example, components derived from animals (eg, artemia); components derived from plants (eg, cat's claw); DNA, DNA salts, RNA, RNA salts. Nucleic acid components such as. The content of the component having a preventive and / or repairing action on DNA damage can be appropriately selected in consideration of the feeling of use on the skin and the effect, but is, for example, about the total amount of the external composition for skin of the present invention. It is 0.001 to 3% by mass, preferably about 0.01 to 1% by mass. When an animal component or a plant component is used, the content is preferably about 0.00001 to 0.1% by mass, more preferably about 0.00001 to 0.1% by mass, based on the total amount of the external composition for skin of the present invention in terms of an extract such as an extract. Is about 0.0001 to 0.01% by mass.

Examples of whitening ingredients include placenta, albutin, kodiic acid, ellagic acid, phytic acid, tranexamic acid, lucinol, chamomile ET, hydroquinone, potassium 4-methoxysalicylic acid salt; linoleic acid and its derivatives; ascorbic acid and its salts, ascorbic acid. Vitamin Cs such as acid derivatives (sodium ascorbic acid phosphate, magnesium ascorbic acid phosphate, ascorbic tetra2-hexyldecanoate, 2-O-ethylascorbic acid, 3-O-ethylascorbic acid, ascorbic acid glucoside, iso Stearyl ascorbic acid disodium, dipalmitate L-ascorbic acid, palmitate ascorbic acid trisodium, glyceryl ascorbic acid, bisglyceryl ascorbic acid, alkyl glyceryl ascorbic acid, etc.), vitamin A or its derivatives, pantothenic acid or its derivatives, etc. Examples of vitamins and the like. Further, a plant component having a whitening effect may be used as a whitening component, and such plant components include iris (iris), almond, aloe, acerola, oolong tea, ages, augon, prune, evening primrose, rosemary, seaweed, and cucumber. Kuchinashi, Kujin, Chlorella, Rice, Rice Haiga, Oryzanol, Rice bran, Saishin, Sansho, Shiso, Shakuyaku, Senkyu, Souhakuhi, Soybean, Natto, Tea, Touki, Tokinsenka, Hamamelis, Benibana, Buttonpi, Yokuinin, Asenyaku Black bean, gentian, genjin, sage, daikon, tsutsuji, parsley, holly, pearl barley, hop, thyme, chow, chimpi, kanzo, chamomile, prunes, shimotsukesou, alpinia katsumadai, murasakikibu, sozuku, gravel fruit, evening primrose, splinter , Kiwi, Pine, Neem, Artichoke, Sugina, Oobaku, Evening Primrose, Evening Primrose, Bilberry, Himefuuro, Akeshisou, Seiyoushiroyanagi, Yukinoshita, Tsubokusa, Rosemary, Lavender, Sanshuyu and the like. When these plant components are used in the external composition for skin of the present invention, the form of the plant components is not particularly limited, but they can usually be used in the form of a plant extract (plant extract), an essential oil, or the like. The names in parentheses described in the plant components are the scientific name, alias or crude drug name of the plant.

In the present invention, such whitening ingredients include placenta, arbutin, ascorbic acid, ellagic acid, phytic acid, tranexamic acid, lucinol, chamomile ET, hydroquinone, potassium 4-methoxysalicylate, and linoleic acid. And its derivatives, ascorbic acid, sodium ascorbic acid, sodium ascorbic acid phosphate, magnesium ascorbic acid phosphate, ascorbic tetra2-hexyldecanoate, 2-O-ethylascorbic acid, 3-O-ethylascorbic acid, ascorbic acid Glucoside, Vitamin A oil, Iris, Almond, Aloe, Acerola, Agetsu, Ogon, Ouren, Otogirisou, Odorikosou, Seaweed, Cuckoo, Chlorella, Rice, Rice Haiga, Oryzanol, Rice bran, Shiso, Shakuyaku, Souhakuhi, Soybean, Tea, Tokinsenka , Hamamelis, Buttonpi, Yokuinin, Kiwi, Sage, Parsley, Hiiragi, Hatomugi, Hop, Thyme, Chouji, Chinpi, Kanzo, Chamomile, Prune, Shimotsukesou, Murasakikibu, Alpinia Katsumadai, Souzuku, Grave fruit, Izayoibara, Togenashi From a group consisting of kiwi, pine, neem, artichoke, sugina, obak, mematsuyoigusa, evening primrose, bilberry, himefuuro, akeshisou, sycamore, rosemary, lavender, sanshuyu, and extracts from these plants. One or more selected species are preferred,
Placenta, arbutin, kodic acid, phytic acid, tranexamic acid, hydroquinone, ascorbic acid, sodium ascorbate, sodium ascorbic acid ester, magnesium ascorbate phosphate, ascorbyl tetra2-hexyldecanoate, 2-O-ethylascorbic acid , 3-O-ethylascorbic acid, ascorbic acid glucoside, iris root extract, almond oil, aloe vera extract, acerola extract, agetsu extract, ginger extract, otogirisou extract, odorikosou extract, seaweed extract, cucumber extract, chamomile extract, shakyaku extract, Souhakuhi extract, soybean extract, cha extract, white cha extract, tokinsenka, hamamelis, yokunin, honeybee extract, hop extract, prune extract, kanzo extract, oil-soluble kanzo extract, shimotsukesou extract, purple kib extract, alpinia katsumadai seed extract, gravel fruit extract , Isayoibara extract, Lemon extract, Kiwi extract, Pine extract, Neem leaf extract, Artichoke extract, Sugina extract, Oobaku extract, Mematsuyoigusa extract, Evening primrose oil, Bilberry leaf extract, Himefuuro extract, Akkesiso extract, Seiyoshiroyanagi extract, Tsubokusa extract, and Sanshuyu fruit. One or more selected from the group consisting of extracts is more preferable.

When the whitening ingredient described above is added to the external composition for skin of the present invention in addition to nicotinamide, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for external use on the skin. It is, for example, about 0.0003 to 10% by mass, preferably about 0.01 to 5% by mass, based on the total amount of the composition. When a plant extract is used, the content is, for example, about 0.00001 to 20% by mass, preferably about 0.0001 to 15% by mass, based on the total amount of the external composition for skin in terms of an extract such as an extract. , More preferably 0.001 to 10% by mass.

Examples of the anti-inflammatory component include allantin, caramine, tranexamic acid, glycyrrhetinic acid or a derivative thereof or a salt thereof (for example, glycyrrhetinic acid, stearyl glycyrrhetinate, etc.), zinc oxide, aminocaproic acid, azulene and a derivative thereof (eg, guaiazulene). , Azulene, etc.), tocopherol acetate, pyridoxin hydrochloride, menthol, camphor, terepine oil, indomethacin, salicylic acid or derivatives thereof, steroids or derivatives thereof or salts thereof (eg, hydrocortisone, prednisolone), ufenamate, bufexamac, ibprofenpiconol, Glycol salicylate, components derived from plants (eg, comfrey, auren, dokudami), and the like can be mentioned. It is preferably one or more selected from allantoin, tranexamic acid, glycyrrhetinic acid, stearyl glycyrrhetinate, aminocaproic acid, azulene and its derivatives or Houttuynia cordata extract, and more preferably selected from allantoin, tranexamic acid and aminocaproic acid. One type or two or more types. When the anti-inflammatory component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.0003 to 10 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably about 0.01 to 5% by mass.

Examples of the antibacterial component include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclosan, triclosan, and photosensitizer. No. 101, Photosensitizer No. 201, Phenoxyethanol, Alkyldiaminoglycine hydrochloride, Cetylpyridinium chloride, Pyroctolamine, Myconazole or a salt thereof, Chlorobutanol, Ethylhexylglycerin, Propinyl iodide butylcarbamate, Capril hydroxamic acid, Fenetyl alcohol, Methylisothiazolinone , Sorbic acid or a salt thereof, cetyltrimethylammonium bromide, β-glycyrrhetinic acid, components derived from plants (for example, clara, rosemary, quail, eucalyptus, etc.) and the like. Preferably, salicylic acid, benzalkonium chloride, ethanol, benzethonium chloride, gluconic acid, isopropylmethylphenol, phenoxyethanol, cetylpyridinium chloride, chlorobutanol, ethylhexylglycerin, propynyl iodide butylcarbamate, capryl hydroxamic acid, potassium sorbate, odor. One or more selected from cetyltrimethylammonium chloride, β-glycyrrhetinic acid, rosemary extract, and eucalyptus extract are preferable. When the antibacterial component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.0003 to 10 mass with respect to the total amount of the external composition for skin of the present invention. %, preferably about 0.01-5% by mass.

Examples of the refreshing agent include menthol and its derivatives, camphor, borneol, geraniol, cineole, anethole, limonene, eugenol and other terpenes (these may be d-form, l-form or dl-form); eucalyptus oil. , Bergamot oil, peppermint oil, cool mint oil, spare mint oil, uikyo oil, camphor oil, keihi oil, rose oil, terpene oil and other essential oils. Of these, a combination with l-menthol, menthyl glyceryl ether, menthol lactate, menthyl 3-hydroxybutyrate, mentoxypropanediol, camphor, eucalyptus oil, peppermint oil, and peppermint oil is preferable.

Organic acids include gluconic acid, aspartic acid, aminoethylsulfonic acid, citric acid, glutamic acid, succinic acid, oxalic acid, fumaric acid, malonic acid, maleic acid, propionic acid, malic acid, salicylic acid, glycolic acid, phytic acid, Examples thereof include tartrate acid, acetic acid, lactic acid, pantothenic acid, glycyrrhetinic acid, alginic acid, ascorbic acid, benzoic acid, adipic acid, glutamic acid, azelaic acid and salts thereof. Examples of the salt include mineral acid salts such as sulfuric acid, hydrochloric acid or phosphoric acid, organic acid salts such as maleic acid or methanesulfonic acid, alkali metal salts such as sodium or potassium, alkaline earth metal salts and ammonium salts. Examples thereof include basic amino acid salts and amine salts such as triethanolamine. Among them, a combination of one or more selected from gluconic acid, citric acid, glutamate, succinic acid, malic acid, salicylic acid, glycolic acid, phytic acid, tartaric acid, lactic acid, glycyrrhetinic acid and salts thereof is more preferable.

Examples of anti-glycation components include Budreja axilaris leaf extract, seaweed fruit extract, edelweiss extract, ginkgo extract, cherry leaf extract, pomegranate extract, sardine extract, sardine extract, sardine extract, dokudami extract, bilberry leaf extract, and the like. Green tea extract, tea extract, marronnier extract, roma chamomile extract, yomogi extract and other plant extracts, evening primrose oil, Amler fruit, fruit juice or their extracts, L-arginine, L-lysine, hydrolyzed casein, hydrolyzable tannin , Carnosin and the like. When the anti-glycation component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.0003 to 10 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably about 0.001 to 5% by mass.

Examples of cell activating components include amino acids such as γ-aminobutyric acid: vitamins such as retinol, thiamine, riboflavin, pyridoxin hydrochloride, and pyrroloquinolinquinones pantothenate; tannins, flavonoids, saponins, allantin, placenta, proteoglycans, etc. Photosensitizer 301, ingredients derived from plants (eg soybean bilberry, lemongrass, aloe vera, chlorella, corn, yogurt, chamomile, dokudami, hop, carrot, etc.); royal jelly, royal jelly extract; whey, yogurt extract, hydrolyzed milk Examples include milky lotion-derived extracts such as proteins and yeast extracts. When the cell activating component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, from about 0.0003 to the total amount of the external composition for skin of the present invention. It is 10% by mass, preferably about 0.001 to 5% by mass.

Convergent components include, for example, metal salts such as myoban, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc paraphenol sulfonate, basic zinc lactate, zinc sulfate, potassium aluminum sulfate; plants (eg seaweed, thyme, thyme, etc. Ingredients derived from tea, oolong tea, green tea, otogirisou, hamamelis, biwa, buttonpi, yukinoshita, luibos, lotus, artichoke, chamomile, eucalyptus, lemon, rosemary, waremokou, etc.) can be mentioned. When the astringent component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.0003 to 20 mass with respect to the total amount of the external composition for skin of the present invention. %, preferably about 0.001-10% by mass.

Antioxidant components include, for example, butyl hydroxyanisole, dibutyl hydroxytoluene, sodium hydrogen sulfite, sodium pyrosulfate, erythorbic acid and its salts, ascorbic acid and its salts, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase. , Superoxide dismutase, thioredoxin, taurine, thiotaurine, hipotaurin, plants (eg, otogirisou, cucumber, bilberry, ginger, kudamonotokeisou, grapefruit, shakuyaku, shimotsukesou, shiso, watermelon, sage, yarrow Ingredients derived from chimpi, Himefuuro, Biwa, Benibana, Buttonpi, Hop, Eucalyptus, Yukinoshita, Louis Boss, Lemongrass, Soybean, Yarrow, Mematsuyoigusa, Rosemary, Lavender, etc. can be mentioned. When the antioxidant component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.00001 to 10% by mass with respect to the total amount of the external composition for skin of the present invention. , It is preferably about 0.0001 to 5% by mass, and more preferably 0.001 to 5% by mass.

Examples of anti-aging components include hydrolyzed soybean protein, retinoids (retinol, retinoic acid, retinal, etc.), pangamic acid, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone. , Peptides (Caprooil Tetrapeptide-3, Oligopeptide-24, etc.), Plants (eg Artichoke, Izayoibara, Seaweed, Bilberry, Shirakaba, Broadleaf Plantain, Touki, Ogon, Otogirisou, Comfrey, Neem, Novara, Ougi, Ingredients derived from (Himefuuro, Bodaiju, Buttonpi, etc.) can be mentioned. Among them, hydrolyzed soybean protein, retinol, retinol acetate, retinol palmitate, caprooil tetrapeptide-3, oligopeptide-24, artichoke leaf extract, seaweed extract, bilberry leaf extract, comfrey leaf extract, neem leaf extract, Himefuuro Extracts are preferred. When the anti-aging component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.0003 to 10 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably about 0.01 to 5% by mass.

Examples of the moisturizing component include amino acids such as alanine, serine, aspartic acid, glycine, proline, hydroxyproline, glucosamine, theanine and arginine and their derivatives; polyhydric alcohols such as glycerin, dipropylene glycol and 1,3-butanediol. Sugar alcohols such as sorbitol, xylitol, erythritol, maltose-sucrose condensate (glucooligosaccharide), hydrolyzed xylan (xylooligosaccharide); glycosyltrehalose, glycerylglucoside, trehalose; ceramide, glucosylceramide, cholesterol, phytosterol, cholesterol derivative, Phospholipid derivatives ,; phospholipids such as lecithin, hydrogenated lecithin; NMF-derived components such as urea; collagen, elastin, keratin, chitin, chitosan and their hydrolysates; hydroxyethylurea; plants (eg, aloe, seaweed, etc.) Ingredients derived from (cuckon, chlorella, lemongrass, chamomile, hamamelis, cha, perilla, grapefruit, amachaduru, etc.) can be mentioned. Among them, glycine, arginine, glycerin, dipropylene glycol, 1,3-butanediol, glycosyl trehalose, ceramide, glucosyl ceramide, cholesterol, cholesterol derivative, phytosterol derivative, hydrogenated lecithin, urea ;; collagen, elastin, keratin, hydroxyethyl A combination of one or more selected from urea, seaweed extract, chamomile extract, hamamelis extract, and amachazuru extract is preferable. When a moisturizing ingredient is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.001 to 20 mass with respect to the total amount of the external composition for skin of the present invention. %, preferably about 0.01-10% by mass.

Examples of the polyhydric alcohol include diols having 2 to 4 or 11 or more carbon atoms and polyhydric alcohols having 3 or more hydroxy groups. For example, glycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-. Butanediol, ethylene glycol, diethylene glycol, isopylene glycol, 1,3-butylene glycol, and the like. Of these, one or a combination of two or more selected from glycerin, propylene glycol, dipropylene glycol, and 1,3-butylene glycol is preferable. When the polyhydric alcohol is blended, its content can be appropriately selected in consideration of the feeling of use on the skin and the moisturizing effect, but for example, about 0.1 to 1 with respect to the total amount of the external composition for skin of the present invention. It is 20% by mass, preferably about 0.5 to 15% by mass.

When, for example, lanolin, urea, and a keratin softening component are blended as the keratin softening component, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but the total amount of the external composition for skin of the present invention. With respect to, for example, 0.0001 to 50% by mass, preferably about 0.001 to 50% by mass, and more preferably about 0.01 to 25% by mass.

Examples of vitamins include retinol derivatives such as retinol, retinol acetate, retinol palmitate, retinol propionate, and retinol linoleate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, and d-δ-toco. Vitamin A such as ferryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate; β, δ-tocopherol, tocopherol nicotinate, dl-α-tocopherol acetate, tocopherol linoleic acid, (linoleic acid / oleic acid) ) Vitamin Es such as tocopherol, (ascorbic / tocopheryl) potassium phosphate; riboflavin, flavin mononucleotide, flavin adenin dinucleotide, riboflavin butyrate, riboflavin tetrabutyric acid, riboflavin 5'-sodium phosphate, riboflavin tetranicotinic acid Vitamin B2s such as esters; nicotinic acids other than the above component (A) such as methyl nicotinate, nicotinic acid, benzyl nicotinate, etc .; ascorbic stearate, disodium isostearyl ascorbyl phosphate, L-ascorbyl dipalmitate, tetra Ascorbyl isopalmitate (ascorbyl tetra2-hexyldecanoate), ascorbyl palmitate trisodium, ascorbic acid, sodium ascorbic acid, dehydroascorbic acid, sodium ascorbic acid ester, magnesium ascorbic acid phosphate, glucoside ascorbic acid, Vitamin Cs such as 2-O-ethylascorbic acid, 3-O-ethylascorbic acid, glyceryl ascorbic acid, bisglyceryl ascorbic acid, alkyl glyceryl ascorbic acid; Classes; Vitamin Ks such as phylloquinone and farnoquinone; Vitamin B1s such as thiamine and salts thereof (for example, dibenzoylthiamine hydrochloride, thiamin hydrochloride, thiamindiphosphate, etc.); pyridoxin hydrochloride, pyridoxin acetate, pyridoxal hydrochloride Vitamin B6s such as pyridoxal phosphate and pyridoxamine hydrochloride, vitamin B12s such as cyanocobalamine, hydroxocobalamine and deoxyadenosylcobalamine; folic acids such as folic acid and pteroylglutamic acid; Pantothenic acids such as lucol (pantenol), D-pantethein, D-pantetin, coenzyme A, pantothenyl ethyl ether, calcium pantethene sulfonate; biotins such as biotin and biocithin; in addition, carnitine, ferulic acid, α- Examples thereof include vitamin-like acting factors such as lipoic acid, orotic acid, γ-oryzanol, pyrroloquinoline quinone, hesperidin and glucosyl herperidine, ubiquinone, and salts thereof. Of these, combinations with vitamin Bs, vitamins C, vitamin Es, vitamin As, and vitamin-like acting factors are preferable, and in particular, pyridoxin hydrochloride, pantothenyl alcohol (pantenol), riboflavin, cyanocobalamine, dl-α-tocopherol acetate, Combination with one or more selected from ascorbic acid palmitate, tetra2-hexyldecanoate ascorbyl, retinol, retinol palmitate, retinol propionate, retinol acetate, pyroquinolinquinone or a salt thereof, ubiquinone, γ-orizanol Is more preferable. When vitamins are blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.001 to 30 mass with respect to the total amount of the external composition for skin of the present invention. %, preferably about 0.01 to 25% by mass, more preferably about 0.01 to 20% by mass.

Examples of blood circulation promoting components include plants (for example, Panax ginseng, Ashitaba, Arnica, Ginkgo, Uikyo, Enmeisou, Dutch oak, Chamomile, Roman chamomile, Carrot, Gentiana, Gobo, Rice, Sanzashi, Shiitake, Seiyousanzashi, Seiyounezu, Senkyu. , Senburi, Thyme, Chouji, Chimpi, Touki, Tounin, Touhi, Carrot, Garlic, Butcher Bloom, Grape, Button, Maronnier, Melissa, Yuzu, Yokuinin, Rosemary, Rosehip, Chimpi, Touki, Touhi, Peach, Anzu, Ingredients derived from walnut, corn); dl-α-tocopherol acetate, tocopherol nicotinate, glucosyl hesperidin, hesperidin. When a blood circulation promoting component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.00001 to 10 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably 0.0001 to 5% by mass, and more preferably about 0.001 to 5% by mass. When a plant-derived component is used, the content is, for example, about 0.00001 to 20% by mass, preferably about 0.0001 to 15% by mass, based on the total amount of the external composition for skin in terms of an extract such as an extract. %, More preferably 0.001 to 10% by mass.

Examples of the sebum-adsorbing component include talc, mica, hydroxyapatite, zinc oxide, aluminum silicate and the like. Of these, mica, hydroxyapatite, and zinc oxide are preferable, and mica is particularly preferable. When the sebum-adsorbing component is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, about 0.001 to 35 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably about 0.1 to 25% by mass.

Examples of the peptide or its derivative include keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, succinylated atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrate. Degraded collagen, elastin-degrading peptide, conchiolin-degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soybean proteolytic peptide, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptide, hydrolysis Wheat protein, casein-degrading peptide, acylated peptide (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.) and the like can be mentioned. Among them, keratin-degrading peptide, hydrolyzed keratin, fish-derived collagen elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, succinylated atelocollagen, elastin-degrading peptide, hydrolyzed silk, soybean proteolytic peptide, hydrolyzed soybean protein. It is more preferable to use one type or a combination of two or more types. When a peptide or a derivative thereof is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, from about 0.0001 to the total amount of the external composition for skin of the present invention. It is 35% by mass, preferably about 0.001 to 10% by mass.

Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, and cystine. , Methionin, leucine, isoleucine, valine, histidine, threonine, tyrosine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosin, creatin, epsilon aminocaproic acid, tryptophan, ornithine, N-stearoyl-L -Sodium glutamic acid, lysine dilauroyl glutamate and salts thereof, di lauroyl glutamate (phytosteryl / octyldodecyl), di lauroyl glutamate (octyldodecyl / phytosteryl / behenyl) and the like can be mentioned. Further, these amino acids or derivatives thereof may be solvates such as hydrates, and may be d-form, l-form, or dl-form. Among them, one kind or two or more kinds selected from l-form amino acids or derivatives thereof are preferable.

In particular, the external composition for skin of the present invention preferably contains acidic mucopolysaccharides such as hyaluronic acids and heparinoids.

Hyaluronic acid obtained by extracting from animal tissues, microorganisms, etc. is generally said to have an average molecular weight of about 1 million or more, and is known to be extremely high molecular weight. In the present invention, such high molecular weight hyaluronic acid may be used, or low molecular weight hyaluronic acid and hyaluronic acid oligosaccharide (4 sugars, 6) obtained by a method such as decomposition of high molecular weight hyaluronic acid and fermentation by microorganisms. Sugars, octasaccharides, etc.) and unsaturated hyaluronic acid (having double bonds at the 4- and 5-positions of D-glucuronic acid) may be used.

The salt of hyaluronic acid or a derivative thereof is also not particularly limited as long as it is pharmacologically or physiologically acceptable, for example, alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, aluminum and the like. Examples include salt with metal. Preferably, a sodium salt, a potassium salt, or a zinc salt is used as the salt of hyaluronic acid or a derivative thereof.
Since such hyaluronic acid, its derivatives, and salts thereof have been developed as raw materials for pharmaceutical cosmetics, such commercially available products can also be used.

Heparinoid means a general term for polysulfated mucopolysaccharides such as chondroitin polysaccharides, and an average of 0.5 to 5 molecules, preferably an average of 0.6 to 3 molecules of sulfuric acid per monosaccharide constituting the mucopolysaccharide. It preferably has a group. More specifically, the heparinoid contains heparin, chondroitin sulfate D called chondroitin polysulfate, chondroitin sulfate E, and the like.

Heparinoids can also be obtained by sulfated mucopolysaccharides, extracted and purified from the internal organs containing the bronchi of animals such as cattle and pigs using an aqueous carrier, and then sulfated as needed. You can also get it by doing things. Since such a heparinoid has been developed as a raw material for pharmaceuticals and cosmetics, such a commercially available product can also be used.

In the present invention, the acidic mucopolysaccharide includes, but is not limited to, hyaluronic acid, low molecular weight hyaluronic acid, hyaluronic acid oligosaccharide (tetrasaccharide), acetylated hyaluronic acid, cationized hyaluronic acid, and hydrolyzed alkyl hyaluronate (C12). -13) Glyceryl, crosslinked hyaluronic acid, carboxymethyl hyaluronic acid, alkylene glycol hyaluronate, dimethylsilanol hyaluronate, heparin analogs and / or salts thereof are preferred, hyaluronic acid, low molecular weight hyaluronic acid, acetylated hyaluronic acid, hyalurone. Hydroxypropyltrimonium acid acid, carboxymethyl hyaluronic acid, propylene glycol hyaluronate, sodium hyaluronate, zinc hyaluronate, low molecular weight zinc hyaluronate, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, and heparin analogs are more preferred. Even more preferred are sodium hyaluronate, zinc hyaluronate, low molecular weight zinc hyaluronate, acetylated hyaluronic acid, hydroxypropyltrimonium hyaluronate, propylene glycol hyaluronate, crosspolymer sodium hyaluronate, and heparin analogs. When the acidic mucopolysaccharide is blended, the content thereof can be appropriately selected in consideration of the feeling of use on the skin and the effect, but for example, 0.0001 to 1 with respect to the total amount of the external composition for skin of the present invention. It is by mass, preferably 0.001 to 0.5% by mass.

Further, in the external composition for skin of the present invention, in addition to the above-mentioned components, components usually used in fields such as pharmaceuticals, quasi-drugs, and cosmetics may be appropriately blended depending on the intended use or dosage form. good. The components that can be blended are not particularly limited, but are, for example, bases or carriers, surfactants, thickeners, antioxidants, preservatives, preservatives, pH adjusters, chelating agents, stabilizers, and irritation reducing agents. , Colorants, dispersants, fragrances and other additives can be added. In addition, these components can be blended individually by 1 type or in any combination of 2 or more types. Further, these contents can be appropriately determined from a conventionally known range within a range that does not impair the effects of the present invention. Further, those corresponding to the following plurality of components can be added as components having any function among them.

As the base or carrier, an aqueous base such as water; liquid paraffin, liquid isoparaffin, squalane, vaseline, paraffin, microcrystallin wax, polybutene, polyethylene powder, gelled hydrocarbon (plastibase, etc.), ozokelite, α-olefin oligomer. , Hydrocarbons such as light liquid paraffin, light iso liquid paraffin; phenyl-modified silicone such as methylpolysiloxane, crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, cyclic silicone such as decamethylcyclopentasiloxane. , Methylhydrogenpolysiloxane, Methyltrimethicone, Dimethiconol, Dimethiconol crosspolymer, Alkyl-modified silicones such as Caprylyl methicone, Cross-linked alkyl-modified silicones, Amino-modified silicones, polyether-modified silicones, Polyglycerin-modified silicones, Cross-linked poly Ether-modified silicone, cross-linked alkyl polyether-modified silicone, silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicon, phenyl Siloxane oils such as modified silicones, silicone resins; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, cholesterol; isostearic acid, lauric acid, myristic acid, Higher fatty acids such as palmitic acid, stearic acid, and bechenic acid; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose; polyvinylpyrrolidone; polyvinylbutyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester Isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, diisopropyl adipate, decyl oleate, isodecyl oleate, hexyl decyl dimethyloctanoate, diisopropyl sebacate, di-2-sebathate Ethylhexyl, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, diisopro adipate Pill, Isotridecyl isononanoate, Cetyl lactate, Isostearyl isostearate, Cholesteryl 12-hydroxystearyl, Cholesteryl stearate, Cholesteryl oleate, Macademia nut fatty acid phytosteryl, Phytosteryl oleate, Dextrin palmitate, Inulin stearate, Hydrogenated jojoba oil, Ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, neopentyl glycol dicaprate, tri2-ethylhexyl trimeritate, tritridecyl trimeritate, trimethylol propane tri-2-ethylhexylate, trimethylol propane triisostearate, Pentaerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane triisostearate, tri (capric acid / capric acid) glyceryl, tri (capric acid / capric acid / myristic acid / stearic acid) Glyceryl, oleyl oleate, di lauroyl glutamate (phytosteryl / octyldodecyl), di lauroyl glutamate (octyldodecyl / phytosteryl / behenyl), triethyl citrate, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), di. Dimer dilinoleic acid, dipentaerythrityl tripolyhydroxystearate, esters such as tri (bechenic acid / isostearic acid / eicosandiic acid) glyceryl; jojoba oil, beeswax, candelilla wax, rice bran, cotton wax, carnauba wax, lanolin Rows such as avocado oil, flaxseed oil, camellia oil, macadamia nut oil, kukui nut oil, hazelnut oil, corn oil, olive oil, saflower oil, kyonin oil, cinnamon oil, jojoba oil, grape seed oil, sunflower oil, almond oil. , Stearic acid, Southernca oil, Rapeseed oil, Sesame oil, Cacao fat, Palm oil, Hardened palm oil, Palm oil, Palm kernel oil, Mokurou kernel oil, Mokurou, Wheat germ oil, Rice germ oil, Rice bran oil, Cotton seed oil, Large Oils and fats such as soybean oil, peanut oil, tea seed oil, evening primrose oil, and stearic acid; polysaccharides such as dextrin and maltodextrin; vinyl-based polymers such as carboxyvinyl polymer and alkyl-modified carboxyvinyl polymer; Lower alcohols such as; sorbitol, xylitol, erythritol, mannitol, etc. Sugar alcohol; water and the like can be mentioned. As the base or carrier selected from these components, one type may be used alone, or two or more types may be used in combination. The amount used thereof is appropriately selected from a range known to those skilled in the art. When the external composition for skin of the present invention contains water, the content thereof is not particularly limited as the amount of water varies depending on the form of the cosmetic. For example, the amount of water is preferably 5 to 99% by mass, more preferably 8 to 95% by mass, and further preferably 10 to 90% by mass with respect to the total amount of the external composition for skin of the present invention.

Examples of the surfactant include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monostearate, tetra-2-ethylhexyl diglycerol sorbitan, sorbitan monooleate, sorbitan monoisostearate, and sorbitan monolaurate; Polyoxyethylene monolaurate (20) sorbitan, polyoxyethylene monolaurate (80) sorbitan, polyoxyethylene monostearate (20) sorbitan, polyoxyethylene monooleate (20) sorbitan, polyoxyethylene isostearate ( 20) Polyoxyethylene sorbitan fatty acid esters such as sorbitan and olive oil fatty acid sorbitan; glycerin fatty acid esters such as glycerin monooleate, glycerin monostearate, and glycerin monomillistate; glycerin alkyls such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether. Ether; polyglycerin fatty acid esters such as diglyceryl monostearate, decaglyceryl decasterate, decaglyceryl decaisostearate, diglyceryl diisostearate; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene Hardened castor oil derivatives such as cured castor oil 40, polyoxyethylene cured castor oil 50, polyoxyethylene cured castor oil 60, polyoxyethylene cured castor oil 80; polyoxyethylene glycerin fatty acid such as polyoxyethylene monococonut oil fatty acid glyceryl Estearic acid: Polyoxyethylene sterol / hydrogenated stearic acid such as polyoxyethylene (20) phytosterol, polyoxyethylene (30) phytosterol, polyoxyethylene (25) phytostanol, polyoxyethylene (30) cholestanol; sucrose fatty acid ester Aether carboxylate, alkyl phosphate ester salt, N-acyl amino acid salt, acylated taurate; amines such as stearylamine and oleylamine; polyoxyethylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl Examples thereof include silicone-based surfactants such as dimethicone and PEG-9 polydimethylsiloxyethyl dimethic acid, or naturally-derived surfactants such as lecithin, hydrogenated lecithin, saponin, sodium surfactinate, cholesterol, and stearic acid. be able to.

Examples of the thickener include vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethyl ether, and carboxyvinyl polymers; methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydrophobization. Cellular thickeners such as hydroxypropyl methylcellulose, carboxymethylcellulose, or carboxyethylcellulose or salts thereof; guar gum, sclerothium gum, tamarind gum, xanthan gum, gellan gum, dextran, pectin, purulan, gelatin, locust bean gum, carrageenan, Agar, alkyl methacrylate copolymer, sodium polyacrylate, bentonite, dextrin fatty acid ester, dimethyl distearyl ammonium hectrite, sodium alginate, propylene glycol alginate, polyethylene glycol, macrogol, (hydroxyethyl acrylate / acryloyl) Examples thereof include a (dimethyltaurine Na) copolymer and a (acryloyldimethyltaurinammonium / vinylpyrrolidone) copolymer. Among them, xanthan gum, alkyl methacrylate copolymer, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydrophobic hydroxypropyl methyl cellulose, carboxyvinyl polymer, alkyl methacrylate copolymer, dimethyl distearyl ammonium hectrite, A (hydroxyethyl acrylate / acryloyldimethyltaurine Na) polymer or a (acryloyldimethyltaurinammonium / vinylpyrrolidone) copolymer is preferable.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, sodium pyrosulfate, ascorbic acid, ascorbic acid derivative, tocopherol, tocopherol derivative, erythorbic acid, sodium erythorbate, and L-cysteine hydrochloride. , Ubiquinones such as coenzyme Q10, lignans such as sesamine, curcumin, capsaicin, gingerol, resveratrol, anthocyanin, cyanidin, bilberry extract and their relatives or derivatives.

Examples of the pH adjuster include inorganic acids (hydrochloride, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), and inorganic bases (potassium hydroxide, hydroxide). (Sodium, etc.), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.) and the like.

Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacy, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphate, etc. , Metaphosphate and the like. Of these, sodium edetate is preferable.

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

Examples of the irritation reducing agent include licorice extract, gum arabic, polyvinylpyrrolidone and the like.

Examples of the colorant include pigment-grade titanium oxide, zinc oxide, iron oxide, organic pigments, talc, sericite, mica, synthetic mica, chromium oxide, and gunjo.

In addition, powder may be blended to improve the feel and impart a make-up effect, and specifically, boron nitride, silica, alumina, aluminum hydroxide, metal soap, silicone powder, polymethylmethyl methacrylate. And so on.

[PH]
The external composition for skin of the present invention usually has a liquid property of pH 2.0 to 9.0, but is preferably pH 3 from the viewpoint of low irritation to the skin and mucous membranes and good skin usability. .0 to 8.5, more preferably pH 4.0 to 8.0, even more preferably pH 4.5 to 7.5, even more preferably pH 5.0 to 7.5.

[Manufacturing method of external composition for skin]
The method for producing the external composition for skin of the present invention is not particularly limited, and in addition to the above-mentioned components (A) to (C), the above-mentioned other components and the like are appropriately selected and blended, and emulsified as necessary by a conventional method. Can go and manufacture.

[Properties / Pharmaceuticals]
The properties of the external composition for skin of the present invention are not particularly limited, and may be liquid, fluid, or semi-solid. Examples of the formulation form include liquids, suspensions, emulsions, creams, emulsions, ointments, gels, liniments, lotions, aerosols, sheets of non-woven fabrics impregnated with chemicals, sticks and the like. It can be a formulation. Among them, emulsions, creams, emulsions, ointments, gels, lotions, sheets and sticks obtained by impregnating non-woven fabrics with chemicals are preferable, and creams, emulsions, ointments and gels are particularly suitable. .. When an oil-based base and an aqueous base are contained, such as emulsions, creams, and ointments, either W / O type or O / W type may be used, but the feeling of use of the external composition for skin of the present invention ( The O / W type is more preferable from the viewpoint of stickiness, spread, moist feeling, freshness, penetration feeling, etc.).

[Use]
Specifically, when it is used as an external composition for pharmaceutical products or cosmetics, for example, cosmetics, milky lotions, gels, creams, beauty liquids, sunscreen cosmetics, packs, masks, hand creams, etc. Body lotions and basic cosmetics such as body creams, wipes, sticks; and cleaning cosmetics such as wash pigments, hand soaps, makeup removers, body shampoos, shampoos, rinses, and treatments. Face makeup cosmetics such as BB cream, foundation, makeup base, lip cosmetics such as lip cream, lip liner, lip gel; hair rinse for hair, hair treatment, hair conditioner, hair gel, hair mousse, hair mist, hair lotion, Examples include hair cosmetics such as styling agents. Of these, external compositions for the skin are particularly preferable. That is, the external composition of the present invention can be a pharmaceutical, quasi-drug, or cosmetic external composition for skin. The formulation form of the external composition for skin is the same as that of the external composition of the present invention. In addition, the bases or carriers, additives, and active ingredients that can be used, and their preferred ones, are the same as in the case of the external composition of the present invention.

[container]
The external composition for skin of the present invention can be contained and used in a container having an appropriately selected shape and material according to the purpose of use and use. Specific examples of the container include a spray type, a bottle type, a tube type, a jar type, a dropper type, a dispenser type, a stick type, a pouch bag, and a cheer pack. Since the external composition for skin of the present invention can be used in a preferable state from the viewpoint of ease of removal from the container, it is possible to increase the degree of freedom in designing a formulation containing a high concentration of nicotinic acid amide. That is, even a high-concentration nicotinic acid amide-containing preparation can be easily used in a wide variety of containers such as sprays, bottles, tubes and dispensers as well as jars and sticks.

Further, as the material of the container, polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, metal (aluminum, etc.) and the like can be exemplified. In addition, these materials are subjected to various coating treatments in consideration of strength, flexibility, weather resistance, stability of components, etc., and these materials are combined or laminated by, for example, mixing them. , Can be used as a container material. Of these, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, and metal (aluminum, etc.) are preferably used.

[How to use]
The external composition for skin of the present invention can be suitably used for the purpose of promoting blood circulation, anti-inflammatory and ceramide synthesis in anticipation of the physiological activity of nicotinamide. Furthermore, it can be expected to have whitening, anti-wrinkle, and anti-aging effects, and is useful as a multifunctional preparation including a whitening agent and a sunscreen. The external composition for skin of the present invention can be used in a known or commonly used dosage and administration in 1 to several divided doses per day depending on the intended use.

[Precipitation suppression method, etc.]
In another embodiment, the present invention can also provide a method for suppressing the precipitation of an external composition for skin containing (A) nicotinic acid amide. (A) Nicotinic acid amide; (B) At least one selected from the group consisting of alkanediol, propanediol, diglycerin, and hydroxyalkylurea having 5 to 10 carbon atoms; and (C) glycyrrhizinic acid, glycyrrhizinic acid. By preparing the composition for external use on the skin containing a salt or an amphoteric compound, it is possible to enhance the skin permeability of the nicotinic acid amide, suppress irritation, and further suppress the precipitation of the external composition on the skin.

As used herein, the term "precipitate" means, for example, a phenomenon in which a component appears as a solid regardless of the form of the external composition for skin of the present invention (for example, a solid precipitate, acicular crystals or a hazy cotton-like substance). A substance, etc.). It can be a visible precipitate. Alternatively, it is also possible to detect precipitation and solution transparency that are difficult to detect visually with a turbidity meter and an ultraviolet visible infrared spectrophotometer (model V-770, manufactured by JASCO Corporation). For example, in the external composition for skin of the present invention, the volatile component may precipitate in the process of volatilizing.

In the present invention, it is also possible to prevent precipitation by evaporating to dryness over time, particularly even when a high concentration of nicotinic acid amide is blended. Precipitation at the edge of the container, the mouth of the bottle, the mouth of the dispenser, the straw part, etc. can be a big problem. That is, the state after the volatile components have volatilized after a certain period of time has remained attached to the product remains as a solid substance, which is not preferable not only in appearance but also in use. For example, when the pharmaceutical product is stored in a jar, the pharmaceutical product adhering to the screw portion of the screw cap of the jar remains as a precipitate, which causes a problem that the screw portion cannot be closed properly. When the pharmaceutical product is contained in a bottle, tube, or dispenser, if a precipitate remains on the mouth of those containers, the precipitate may deteriorate the feeling of use and damage the skin at the next use. Furthermore, if solid precipitates remain in the mouth of the container and especially in the straw of the dispenser, the pharmaceutical product becomes clogged.

The formation of such solids not only on the container but also on the skin after application results in deterioration of the effect on the skin and the feeling of use.

According to the present invention, such a problem can be prevented, and a preparation which can be applied to various container forms and has a high degree of freedom in prescription can be prepared.

Precipitation suppression also includes preventing, delaying, and reducing such precipitation. Due to such precipitation suppression, when the external composition for skin is packed in a container, the dry solid matter adheres to the container lid such as a jar or a clogging at the outlet of the container, which adversely affects the usability, appearance, or actual function. Can be prevented.

Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples.

The components used in the examples are as follows.

2-Methylloyloxyethyl phosphorylcholine / butyl methacrylate copolymer: Lipidure-PMB (BG) (manufactured by NOF CORPORATION)
Polyoxybutylene polyoxyethylene polyoxypropylene methylglucoside: Wilbride MG2070 (manufactured by NOF CORPORATION)

[Skin permeability and irritation test]
After preparing the compositions of the reference example, the reference example, and the reference comparative example shown in Table 1, a permeability test and a cytotoxicity test were carried out on three-dimensional cultured skin.

(Permeability test)
Add 0.5 mL / well of the dedicated assay medium attached to the lower part of the trans well (trans well for 24 well plate) of the human 3D cultured epidermis LabCyte EPI-MODEL24 (Japan Tissue Engineering), and add 37 ° C. (5). Pre-cultured at 10% CO ₂ ) for 18-22 hours.

The dedicated assay medium was then replaced with 0.5 mL PBS (phosphate buffered saline) and pre-incubated in a constant temperature bath at 37 ° C. for 30 minutes. Further, PBS was replaced with the same amount of fresh PBS, and 0.1 mL of each composition was added directly to the upper part of the cells. Here, starting from the time when the composition was added, it was set to zero.

Then, 240 minutes later, 0.3 mL of the solution was sampled from the bottom. The sampled liquid was quantified using HPLC, and the permeability coefficient (P) was calculated based on the following formula.
The administered medium, PBS, and composition were all heated to 37 ° C. before administration.
P = (ΔQ / Δt) × (1 / C ₀ ) × (1 / Area)
In the above formula, Q represents the permeation amount (μg), t represents the time (minutes), ΔQ / Δt represents the nicotinic acid amide permeation rate (μg / min), and the cumulative permeation amount of the drug-a straight line of the time curve. It is calculated as the inclination of the part. Further, C ₀ represents the initial concentration (g / mL) of the administered nicotinic acid amide, and Area represents the permeation area (0.3215 cm ² ).
Further, the ratio of the transmission coefficient (Ps) containing various components and the transmission coefficient (Pc) (reference example) not containing various components was calculated based on the following formula, and this was used as the Enhancement Ratio (ER).
ER = Ps / Pc

(Cytotoxicity test)
After carefully washing the transwell after the above sampling with PBS, 0.5 mL of PBS under the transwell (trans well for 24 well plate) was added to (3- (4,5-Dimethlythiazol-2-yl)-. It was replaced with 2,5-Diphenyltellazolium Bromide solution (MTT solution) and then incubated at 37 ° C. for 3 hours in the dark. The MTT solution was prepared by dissolving 0.5 mg of MTT in 1 mL of PBS. Then, the human three-dimensional cultured epidermis exfoliated from the transwell was transferred to a microtube, 0.3 mL of isopropanol was added, and then the mixture was incubated in a cool and dark place for 15 hours or more to extract the dye. The extracted dye was Corona Electric Co., Ltd. The absorbance was measured using the microplate reader of No. 1 (measurement wavelength: 570 nm, 650 nm). Based on the measured values, the cell viability was calculated using the following formula, and the cytotoxicity of the composition was evaluated.

Measured values = [(absorbance at 570 nm for each sample treatment group)-(absorbance at 650 nm for each sample treatment group)]-[(absorbance at 570 nm for isopropanol)-(absorbance at 650 nm for isopropanol)]
Cell viability (%) = 100 x (measured value in each sample treatment group) / (measured value in PBS treatment group)

Table 1 also shows the evaluation results for both permeability and cytotoxicity.

Here, the permeability ratio is a value represented by ER = Ps / Pc as described above, and is a value obtained by dividing the value of ER1 of the reference example or the reference comparative example by the value of ER of the reference example.
Stimulation suppression effect = ratio of survival rate = (survival rate of test cases / survival rate of reference cases)
Survival rate ratio is less than × 0.95 △ 0.95 or more and less than 1.05 〇 1.05 or more and less than 1.15 ◎ 1.15 or more

Both permeability and stimulation effect = (permeability ratio) / (1 / survival ratio)
× 1 or less △ 1 or more and less than 1.05 〇 1.05 or more and less than 1.2 ◎ 1.2 or more

Compared with the reference example, it was found that the irritation inhibitory effect can be achieved by the combined use of 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, dipotassium glycyrrhizinate, pentanediol, or propanediol. Furthermore, it was confirmed that both low irritation and permeability can be achieved. On the other hand, the use of PEG-1500 does not achieve both of these.

基準例に比べて、実施例の組成物では、低刺激と浸透性の両立がさらにバランス良く達成できることが分かった。 Next, the compositions of Examples shown in Table 2 were prepared, and the compatibility between permeability and cytotoxicity was evaluated in the same manner as described above. The results are also shown in Table 2.

Compared with the reference example, it was found that the composition of the example can achieve both low irritation and permeability in a more balanced manner.

(Usage test)
Nicotinic acid amide alone was irritating, and the combination of 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer and nicotinic acid amide, or pentanediol and nicotinic acid amide alleviated the irritation. In addition, the combination of pentanediol, 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer, and nicotinic acid amide reduced irritation.

[Precipitation suppression test]
The compositions shown in Tables 3 to 4 were prepared by a conventional method, and 2.5 g of each sample was placed in a polystyrene weighing pan. These compositions were stored in a constant temperature bath at 70 ° C. for 15 hours to evaporate the volatile components. The presence or absence of precipitation on the weighing pan after evaporation was visually confirmed.

<Evaluation criteria>
〇 No precipitation △ Slight precipitation × Large precipitation XX State in which the precipitate evaporates to dryness The results are also shown in Tables 3 to 7. All figures in the table are mass%.

As shown in Tables 3 to 7, a problem was found that precipitation occurred in the compositions of Comparative Examples. On the other hand, in the composition of the example, it was found that precipitation was suppressed.

[Formulation example]
The external composition for skin of the present invention was prepared based on the formulations shown in Table 8 below. The numerical value in the table means mass%.

いずれの製剤例においても、使用感が良好な皮膚外用組成物が得られる。

In any of the pharmaceutical examples, a composition for external use on the skin having a good feeling of use can be obtained.

Claims (5)

(A) Nicotinic acid amide;
(B) At least one selected from the group consisting of alkanediols having 5 to 10 carbon atoms, propanediols, diglycerins, and hydroxyalkylureas; and (C) glycyrrhizic acid, salts of glycyrrhizic acid, and amphoteric compounds. An external composition for skin containing at least one selected from the group consisting of
A composition for external use on the skin, wherein the amphipathic compound is one or more selected from the group consisting of a compound represented by the following general formula (I), a phosphorylcholine-containing polymer, and a divalent carboxylic acid ester.

(During the ceremony,
Z means a residue obtained by removing n hydroxy groups from a hydrogen atom or a hydroxy compound having 1 to 30 carbon atoms;
AO means an oxyalkylene group having 3-4 carbon atoms;
EO means oxyethylene group;
BO means an oxyalkylene group having 4 carbon atoms;
n means 1-9;
a, b and c mean the average number of moles of AO, EO and BO, respectively, and are 0 to 200 independently. However, a, b and c are not all 0. Further, when n is 2 or more, the plurality of a, b and c may be the same or different. When Z is a hydrogen atom, n is 1.
AO and EO may be added randomly or in the form of blocks. ). The component (B) is at least one selected from the group consisting of 1,2-pentanediol, 1,2-hexanediol, diglycerin, and 1,3-propanediol.
The component (C) is glycyrrhizinic acid, a salt of glycyrrhizinic acid, a compound represented by the general formula (I), a phosphorylcholine-containing polymer, polyglyceryl-10 (eicosane diic acid / tetradecanedioic acid), and biscyclohexanedicarboxylic acid. The external composition for skin according to claim 1, which is one selected from the group consisting of ethoxydiglycol. The component (B) is at least one selected from the group consisting of 1,2-pentanediol and 1,3-propanediol.
The composition for external use on the skin according to claim 2, wherein the component (C) is one selected from the group consisting of glycyrrhizic acid, a salt of glycyrrhizic acid, and a phosphorylcholine-containing polymer. The composition for external use on the skin according to claims 1 to 3, wherein the content of the component (A) is 3% by mass or more. The composition for external use on the skin according to any one of claims 1 to 4, wherein the total content of the paraoxybenzoic acid ester is 0.1% by mass or less.