JP2014237708A - Whitening external preparation, skin penetration accelerator of water-soluble whitening component, and skin whitening method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a whitening external preparation, such as a whitening cosmetic, allowing skin penetration property of a whitening component and rapid passage of a lot of whitening components through a horny layer, and exhibiting high whitening effect.SOLUTION: A whitening external preparation uses at least one alkylene oxide derivative represented by the formula (I) in combination with a water-soluble whitening component. (In the formula, Z is a residue where a hydroxy group is removed from a compound having 3 to 9 hydroxy groups; AO is a C3 to 4 oxyalkylene group; EO is an oxyethylene group; BO is a C4 oxyalkylene group; a is 3 to 9; l, m and n are an average addition molar number of AO, EO and BO respectively, where 1≤l≤50, 1≤m≤50 and 0.5≤n≤5; the weight ratio (AO/EO) of AO to EO is 1/5 to 5/1; and AO and EO may be added in a random or block state.)

Description

  TECHNICAL FIELD The present invention relates to a whitening external preparation such as a cosmetic whose skin permeability of a water-soluble whitening component is improved, a skin penetration enhancer of a water-soluble whitening component, and a skin whitening method.

  As a moisturizing agent having excellent feel and moisturizing property and keeping moisture after washing, International Publication No. 2006/038724 describes an alkylene oxide derivative represented by the following formula (I).

（式中、
Ｚは３〜９個の水酸基を有する化合物の水酸基を除いた残基を表し；
ＡＯは炭素数３〜４のオキシアルキレン基を表し；
ＥＯはオキシエチレン基を表し；
ＢＯは炭素数４のオキシアルキレン基を表し；
ａは３〜９を表し；
ｌ、ｍ及びｎは、それぞれ、ＡＯ、ＥＯ及びＢＯの平均付加モル数であって、１≦ｌ≦５０、１≦ｍ≦５０及び０．５≦ｎ≦５であり；
ＡＯとＥＯとの重量比（ＡＯ／ＥＯ）は１／５〜５／１であり；
ＡＯ及びＥＯはランダム状又はブロック状に付加していてもよい）

(Where
Z represents a residue excluding a hydroxyl group of a compound having 3 to 9 hydroxyl groups;
AO represents an oxyalkylene group having 3 to 4 carbon atoms;
EO represents an oxyethylene group;
BO represents a oxyalkylene group having 4 carbon atoms;
a represents 3-9;
l, m and n are the average added moles of AO, EO and BO, respectively, 1 ≦ l ≦ 50, 1 ≦ m ≦ 50 and 0.5 ≦ n ≦ 5;
The weight ratio of AO to EO (AO / EO) is 1/5 to 5/1;
(AO and EO may be added in random or block form)

The alkylene oxide derivative of the above formula (I) does not have a sticky feeling and provides a refreshing feel, and therefore can be suitably used as a base for various moisturizing cosmetics, particularly a lotion. For example, Japanese Patent Application Laid-Open No. 2006-199665 essentially includes an alkylene oxide derivative corresponding to the above formula (I) and a water-soluble polymer compound, and maintains a moisturizing effect, a rough skin improving effect, a skin protecting effect, and It describes a lotion that is excellent in wrinkle-suppressing effect, gives skin firmness and transparency, makes the skin smooth, and has excellent temporal stability (note that whitening cosmetics are not described at all) It has not been).
International Publication No. 2006/038724 Pamphlet JP 2006-199665 A

  By the way, pigmentation of skin spots, freckles, etc. is caused by abnormal secretion of hormones, ultraviolet rays, inflammation, etc., which activates the melanin production signal transmission circuit in the epidermis pigment cells and produces tyrosinase, which is the main enzyme producing melanin. This occurs because melanin is excessively deposited in the epidermis due to the increased expression.

  Conventionally, ascorbic acid, ascorbic acid glucoside and other ascorbic acid derivatives, kojic acid, ellagic acid, resorcin and its derivatives, and other whitening components are applied to the skin as a countermeasure against such pigmentation. Used as an active ingredient in cosmetics.

  In order for these whitening components to exert a whitening effect, the whitening component should reach as much as possible the epidermal pigment cells that are the cause of excessive melanin production and the stimulus transmission pathway to the epidermal pigment cells. In order to do so, the whitening component must first pass through the stratum corneum on the skin surface.

  However, the stratum corneum has a high barrier property to protect the inside of the skin from the outside, and depending on the whitening component, it may be difficult to pass through the stratum corneum quickly. Therefore, it is required to allow as much whitening component as possible to pass through the stratum corneum as quickly as possible.

  Accordingly, an object of the present invention is to provide a whitening external preparation such as a whitening cosmetic composition that has a high skin whitening component, and many whitening ingredients can quickly pass through the stratum corneum and exhibit a high whitening effect. There is to do.

（式中、
Ｚは３〜９個の水酸基を有する化合物の水酸基を除いた残基を表し；
ＡＯは炭素数３〜４のオキシアルキレン基を表し；
ＥＯはオキシエチレン基を表し；
ＢＯは炭素数４のオキシアルキレン基を表し；
ａは３〜９を表し；
ｌ、ｍ及びｎは、それぞれ、ＡＯ、ＥＯ及びＢＯの平均付加モル数であって、１≦ｌ≦５０、１≦ｍ≦５０及び０．５≦ｎ≦５であり；
ＡＯとＥＯとの重量比（ＡＯ／ＥＯ）は１／５〜５／１であり；
ＡＯ及びＥＯはランダム状又はブロック状に付加していてもよい）
で表される、少なくとも１つのアルキレンオキシド誘導体、及び
（ｂ）少なくとも１つの水溶性美白成分
を含む美白用外用剤によって達成される。 The purpose of the present invention is to
(a) Formula (I) below:

(Where
Z represents a residue excluding a hydroxyl group of a compound having 3 to 9 hydroxyl groups;
AO represents an oxyalkylene group having 3 to 4 carbon atoms;
EO represents an oxyethylene group;
BO represents a oxyalkylene group having 4 carbon atoms;
a represents 3-9;
l, m and n are the average added moles of AO, EO and BO, respectively, 1 ≦ l ≦ 50, 1 ≦ m ≦ 50 and 0.5 ≦ n ≦ 5;
The weight ratio of AO to EO (AO / EO) is 1/5 to 5/1;
(AO and EO may be added in random or block form)
And (b) an external preparation for whitening comprising at least one water-soluble whitening component.

（式中、
Ｚは３〜９個の水酸基を有する化合物の水酸基を除いた残基を表し；
ＡＯは炭素数３〜４のオキシアルキレン基を表し；
ＥＯはオキシエチレン基を表し；
ＢＯは炭素数４のオキシアルキレン基を表し；
ａは３〜９を表し；
ｌ、ｍ及びｎは、それぞれ、ＡＯ、ＥＯ及びＢＯの平均付加モル数であって、１≦ｌ≦５０、１≦ｍ≦５０及び０．５≦ｎ≦５であり；
ＡＯとＥＯとの重量比（ＡＯ／ＥＯ）は１／５〜５／１であり；
ＡＯ及びＥＯはランダム状又はブロック状に付加していてもよい）
で表される、少なくとも１つのアルキレンオキシド誘導体からなる、水溶性美白成分の皮膚浸透促進剤によっても達成できる。 In addition, the object of the present invention is to provide

(Where
Z represents a residue excluding a hydroxyl group of a compound having 3 to 9 hydroxyl groups;
AO represents an oxyalkylene group having 3 to 4 carbon atoms;
EO represents an oxyethylene group;
BO represents a oxyalkylene group having 4 carbon atoms;
a represents 3-9;
l, m and n are the average added moles of AO, EO and BO, respectively, 1 ≦ l ≦ 50, 1 ≦ m ≦ 50 and 0.5 ≦ n ≦ 5;
The weight ratio of AO to EO (AO / EO) is 1/5 to 5/1;
(AO and EO may be added in random or block form)
It can also be achieved by a skin penetration enhancer of a water-soluble whitening component comprising at least one alkylene oxide derivative represented by:

  In the above formula (I), AO and EO may be added randomly, and AO is preferably an oxypropylene group. Furthermore, in the above formula (I), the compound having 3 to 9 hydroxyl groups is preferably glycerin.

  The water-soluble whitening component is preferably ascorbic acid or a derivative thereof.

  The external preparation of the present invention can be a cosmetic (cosmetic composition) or a skin external preparation.

  Moreover, this invention relates also to the skin whitening method including apply | coating said external preparation for whitening to skin.

  According to the present invention, since the alkylene oxide derivative of the above formula (I) improves the stratum corneum permeability of the water-soluble whitening component, the skin permeability of the water-soluble whitening component is promoted. Therefore, according to the present invention, since many water-soluble whitening components can be delivered into the skin, a high whitening effect can be exhibited.

  The present invention is based on the novel finding that an alkylene oxide derivative having a specific structure promotes skin penetration of a water-soluble whitening component. Therefore, the external preparation for whitening of the present invention essentially contains the alkylene oxide derivative and the water-soluble whitening component, and the skin penetration enhancer of the water-soluble whitening component of the present invention essentially contains the alkylene oxide derivative.

（式中、
Ｚは３〜９個の水酸基を有する化合物の水酸基を除いた残基を表し；
ＡＯは炭素数３〜４のオキシアルキレン基を表し；
ＥＯはオキシエチレン基を表し；
ＢＯは炭素数４のオキシアルキレン基を表し；
ａは３〜９を表し；
ｌ、ｍ及びｎは、それぞれ、ＡＯ、ＥＯ及びＢＯの平均付加モル数であって、１≦ｌ≦５０、１≦ｍ≦５０及び０．５≦ｎ≦５であり；
ＡＯとＥＯとの重量比（ＡＯ／ＥＯ）は１／５〜５／１であり；
ＡＯ及びＥＯはランダム状又はブロック状に付加していてもよい）
で表される。上記のアルキレンオキシド誘導体は単一種類であってもよく、若しくは、複数種類の混合物であってもよい。 The alkylene oxide derivative used in the present invention has the following formula (I):

(Where
Z represents a residue excluding a hydroxyl group of a compound having 3 to 9 hydroxyl groups;
AO represents an oxyalkylene group having 3 to 4 carbon atoms;
EO represents an oxyethylene group;
BO represents a oxyalkylene group having 4 carbon atoms;
a represents 3-9;
l, m and n are the average added moles of AO, EO and BO, respectively, 1 ≦ l ≦ 50, 1 ≦ m ≦ 50 and 0.5 ≦ n ≦ 5;
The weight ratio of AO to EO (AO / EO) is 1/5 to 5/1;
(AO and EO may be added in random or block form)
It is represented by The alkylene oxide derivative may be a single type or a mixture of a plurality of types.

  In the alkylene oxide derivative represented by the formula (I), Z is a residue excluding the hydroxyl group of the compound having 3 to 9 hydroxyl groups, and a is the number of hydroxyl groups of the compound of Z and is 3 to 9. As a compound having 3 to 9 hydroxyl groups, for example, if a = 3, glycerin, trimethylolpropane, if a = 4, erythritol, pentaerythritol, sorbitan, alkylglycoside, diglycerin, a = 5 Examples include xylitol, dipentaerythritol, sorbitol, inositol if a = 6, sucrose, trehalose if a = 8, maltitol if a = 9, and mixtures thereof. Preferably, Z is a residue excluding the hydroxyl group of the compound having 3 to 6 hydroxyl groups, and satisfies 3 ≦ a ≦ 6. As the compound having 3 to 9 hydroxyl groups, glycerol and trimethylolpropane are preferable, and glycerol is particularly preferable. In addition, in a <= 2, there exists a tendency for the mixing | blending stability to an oil-based formulation to deteriorate that it is inferior to compatibility with oil-based components, such as fats and oils. When 10 ≦ a, a sticky feeling is generated.

  AO is an oxyalkylene group having 3 to 4 carbon atoms. Examples include oxypropylene group, oxybutylene group (oxy n-butylene group, oxyisobutylene group, oxy t-butylene group), oxytrimethylene group, oxytetramethylene group. Groups and the like. An oxypropylene group, an oxybutylene group, and more preferably an oxypropylene group.

  l is the average added mole number of AO, and 1 ≦ l ≦ 50, preferably 2 ≦ l ≦ 20. m is an average added mole number of EO, and 1 ≦ m ≦ 50, preferably 2 ≦ m ≦ 20. If l is 0, a sticky feeling is produced, and if it exceeds 50, the moisturizing effect is lowered, which is not preferable. Further, if m is 0, the moisturizing effect is lowered, and if it exceeds 50, a sticky feeling is generated, which is not preferable.

  The weight ratio (AO / EO) between AO and EO is 1/5 to 5/1, preferably 1/4 to 4/1. If it is less than 1/5, a sticky feeling is produced, and if it is greater than 5/1, the moisturizing feeling is lowered, which is not preferable. The order in which AO and EO are added is not particularly specified, and they may be added in blocks or randomly. In order to obtain a more excellent rough skin prevention effect, those added randomly are preferable.

  BO is an oxyalkylene group having 4 carbon atoms, and examples thereof include an oxybutylene group (oxy n-butylene group, oxyisobutylene group, oxy t-butylene group), an oxytetramethylene group, and the like. An oxybutylene group is preferred.

n is the average added mole number of BO, 0.5 <n ≦ 5, preferably 0.8 ≦ n ≦ 3, and more preferably 1 ≦ n ≦ 3. If it is 0.5 or less, a sticky feeling is produced, and if it exceeds 5, the moisturizing feeling is lowered. In the formula (I), (BO) _n needs to be bonded to a terminal hydrogen atom.

  The alkylene oxide derivative represented by the formula (I) can be produced by a known method. For example, it can be obtained by subjecting a compound having 3 to 9 hydroxyl groups to addition polymerization of ethylene oxide and an alkylene oxide having 3 to 4 carbon atoms and then reacting the alkylene oxide having 4 carbon atoms. In addition, in the stage of addition polymerization of ethylene oxide and alkylene oxide having 3 to 4 carbon atoms to a compound having 3 to 9 hydroxyl groups, ethylene oxide and alkylene oxide may be randomly polymerized, or block polymerization. May be.

（式中、
Ｇｌｙはグリセリンから水酸基を除いた残基を表し；
ＰＯはオキシプロピレン基を表し；
ＥＯはオキシエチレン基を表し；
ｓおよびｔはそれぞれＰＯおよびＥＯの平均付加モル数であって、１〜５０の値であり、
ＰＯとＥＯとの質量比（ＰＯ／ＥＯ）は１／５〜５／１であって、
ＢＯは炭素数４のオキシアルキレン基を表し；
ｕはＢＯの平均付加モル数であって、０．５〜５の値である）
のアルキレンオキシド誘導体（ポリオキシブチレンポリオキシエチレンポリオキシプロピレングリセロール）が挙げられる。 Among the alkylene oxide derivatives represented by the formula (I), preferable alkylene oxide derivatives include, for example, the following formula (II):

(Where
Gly represents a residue obtained by removing a hydroxyl group from glycerin;
PO represents an oxypropylene group;
EO represents an oxyethylene group;
s and t are the average added moles of PO and EO, respectively, and have a value of 1-50,
The mass ratio of PO to EO (PO / EO) is 1/5 to 5/1,
BO represents a oxyalkylene group having 4 carbon atoms;
u is the average number of moles added of BO, and is a value of 0.5-5)
And alkylene oxide derivatives (polyoxybutylene polyoxyethylene polyoxypropylene glycerol).

  The alkylene oxide derivative of the formula (II) is obtained by adding propylene oxide and ethylene oxide to glycerin at a ratio of 3 to 150 molar equivalents to glycerin, and then converting the alkylene oxide having 4 carbon atoms to 1.5 to It is obtained by adding at a ratio of 15 molar equivalents.

  When these alkylene oxides are added to glycerin, an addition reaction is performed using an alkali catalyst, a phase transfer catalyst, a Lewis acid catalyst, or the like. In general, it is preferable to use an alkali catalyst such as potassium hydroxide.

  Of the alkylene oxide derivatives represented by the formula (I), more preferred are those in which 6 to 10 mol of ethylene oxide and 3 to 7 mol of propylene oxide are added to glycerin, and then 2 to 4 mol of butylene oxide is added. It is a thing.

  Even more preferred among the alkylene oxide derivatives of formula (I) is polyoxybutylene in which 8 moles of ethylene oxide and 5 moles of propylene oxide are added to glycerin and then 3 moles of butylene oxide are added. It is polyoxyethylene polyoxypropylene glycerol and is called PEG / PPG / polybutylene glycol-8 / 5/3 glycerin under the INCI name. PEG / PPG / polybutylene glycol-8 / 5/3 glycerin is commercially available from Nippon Oil & Fat Co., Ltd. under the name WILBRIDE S-753.

  The blending amount of the alkylene oxide derivative represented by the formula (I) in the whitening external preparation of the present invention is not particularly limited, but usually 0.1 to 30 weights based on the total weight of the whitening external preparation. %, Preferably 5 to 25% by weight, more preferably 10 to 20% by weight.

  The blending amount of the alkylene oxide derivative represented by the formula (I) in the skin permeation enhancer of the present invention is not particularly limited, but is usually 10 to 100% by weight based on the total weight of the skin permeation enhancer. Yes, preferably 20 to 100% by weight, more preferably 50 to 100% by weight. The skin penetration enhancer of the present invention is preferably composed only of an alkylene oxide derivative represented by the formula (I) (100% by weight).

  As long as the water-soluble whitening component contained in the whitening external preparation of the present invention and the water-soluble whitening component to be promoted by the skin permeation enhancer of the present invention are water-soluble, any whitening component may be used. it can. Here, the “whitening component” means a component that effectively decolorizes and / or whitens human skin. In particular, human skin that has a stain due to brown pigment due to external factors, or a stain due to internal factors such as aging, or a human who intends to counter the onset of brown coloring due to melanin production after UV irradiation, etc. Applied to the skin. Water-soluble whitening components have a common property of being water-soluble and show similar behavior. A single type of water-soluble whitening component may be used, or a mixture of two or more types may be used.

  Examples of the water-soluble whitening component include ascorbic acid or a derivative thereof, kojic acid or a derivative thereof, tranexamic acid or a derivative thereof, resorcin or a derivative thereof, alkoxysalicylic acid or a salt thereof, adenosine monophosphate or a salt thereof, hydroquinone or a salt thereof Glycosides and derivatives thereof, glutathione, 4- (4-hydroxyphenyl) -2-butanol, magnolignan (5,5′-dipropyl-biphenyl-2,2′-diol), placenta extract, chamomile extract, etc. Can be mentioned.

  Ascorbic acid has D or L form, and L form is used preferably. Ascorbic acid is also called vitamin C, and has a melanin production inhibitory action due to its strong reducing action. The derivative of ascorbic acid may be a salt of ascorbic acid, and the salt of ascorbic acid is preferably selected from sodium ascorbate, magnesium ascorbyl phosphate, and sodium ascorbyl phosphate. The derivative of ascorbic acid may be a glycoside of ascorbic acid or an ester of ascorbic acid. Examples of the glycoside of ascorbic acid include ascorbyl glucoside. Examples of the ester of ascorbic acid include silyl ester of ascorbic acid, tocopheryl ester of ascorbic acid, and alkyl ester of ascorbic acid. As an alkyl ester of ascorbic acid, preferably, ascorbic acid methyl ester or ascorbic acid ethyl ester can be used. In particular, ascorbyl glucoside is preferable. Ascorbic acid or its derivative can use 1 type (s) or 2 or more types.

  As a derivative of ascorbic acid, specifically, for example, 5,6-di-O-dimethylsilylascorbate commercially available under the name PRO-AA from Exsymol; commercially available under the name SEPIVITAL EPC from Senju Pharmaceutical Co., Ltd. Dl-α-tocopheryl-2-l-ascorbyl phosphate; sodium ascorbyl phosphate commercially available under the name Stay-C50 from Roche; ascorbyl glucoside commercially available from Hayashibara Biochemical Research Institute; 3-O-ethyl Examples include ascorbic acid.

  Ascorbic acid or a derivative thereof is preferably used in combination with a copolymer of maleic anhydride and styrene. In particular, it is preferable that at least a part of the maleic anhydride unit of the copolymer is hydrolyzed. The hydrolyzed maleic anhydride unit may be in the form of an alkali salt such as sodium salt, potassium salt or lithium salt. The maleic anhydride unit preferably occupies 0.4 to 0.9 mole of the entire copolymer as 1 mole, and the maleic anhydride unit and the styrene unit are preferably in a ratio of 50:50. . In particular, the maleic anhydride unit and the styrene unit are preferably 50:50 and are in the form of ammonium salt or sodium salt. By using in combination with the copolymer, the stability of ascorbic acid or a derivative thereof is improved. Examples of the copolymer include, for example, a copolymer of styrene / maleic anhydride (50/50) in the form of 30% ammonium salt in water, commercially available as part number SMA1000H (registered trademark) by Atofina or part number SMA1000HNa (registered by Atofina). A styrene / maleic anhydride (50/50) copolymer in the form of 40% sodium salt in water can be used as a trademark. The copolymer is used in a concentration of 0.1 to 20% by weight, preferably 0.1 to 10% by weight, based on the total weight of the whitening external preparation.

  Examples of the derivative of kojic acid include kojic acid glucoside.

  Examples of the derivative of tranexamic acid include a dimer of tranexamic acid (for example, trans-4- (trans-aminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid), an ester of tranexamic acid and hydroquinone (for example, trans-4- Aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester), ester form of tranexamic acid and gentisic acid (for example, 2- (trans-4-aminomethylcyclohexylcarbonyloxy) -5-hydroxybenzoic acid and its salt), tranexamic acid (E.g., trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salt, trans-4- (P-methoxybenzoyl) aminomethylcyclohexanecarboxylic acid and its salt, trans 4-guanidino-methylcyclohexanecarboxylic acid and salts thereof) and the like.

  Examples of the resorcin derivative include 4-n-butylresorcinol (lucinol).

  Alkoxysalicylic acid is one in which any hydrogen atom at the 3-position, 4-position or 5-position of salicylic acid is substituted with an alkoxy group, and the alkoxy group is preferably a methoxy group, an ethoxy group, a propoxy group, or an isopropoxy group. , Butoxy group or isobutoxy group, more preferably methoxy group or ethoxy group. Specific examples of compound names include 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxysalicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4-butoxysalicylic acid, 5-methoxysalicylic acid , 5-ethoxysalicylic acid, 5-propoxysalicylic acid and the like. Although it does not specifically limit as a salt of alkoxy salicylic acid, For example, salts, such as ammonium salt and an amino acid salt other than alkali metal salts or alkaline-earth metal salts, such as sodium salt, potassium salt, and calcium salt, are mentioned. The potassium salt of 4-methoxysalicylic acid is preferred.

  Examples of adenosine monophosphate or a salt thereof include adenosine monophosphate disodium.

  Examples of hydroquinone glycosides include hydroquinone α-D-glucose, hydroquinone β-D-glucose, hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α-D-galactose, hydroquinone β-D- Hexasaccharide glycosides such as galactose, hydroquinone α-L-galactose, hydroquinone β-L-galactose; hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α-L-ribose, hydroquinone β-L- Pentose glycosides such as ribose, hydroquinone α-D-arabinose, hydroquinone β-D-arabinose, hydroquinone α-L-arabinose, hydroquinone β-L-arabinose; hydroquinone α-D-glucosamine, hydroquinone β- -Glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L-glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine, hydroquinone α-L-galactosamine, hydroquinone β-L-galactosamine, etc. Hydroquinone α-D-glucuronic acid, hydroquinone β-D-glucuronic acid, hydroquinone α-L-glucuronic acid, hydroquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone β-D-galacturonic acid, Examples thereof include uronic acid glycosides such as hydroquinone α-L-galacturonic acid and hydroquinone β-L-galacturonic acid. Among these, hydroquinone β-D-glucose (hereinafter referred to as “arbutin”) is preferable. Examples of the hydroquinone or its glycoside derivative include hydroquinone or its glycoside salt. In particular, examples of arbutin derivatives include 6-O-caffeoyl arbutin.

  As the water-soluble whitening component, L-ascorbic acid or a derivative thereof, kojic acid or a derivative thereof, tranexamic acid or a derivative thereof, arbutin or a derivative thereof, lucinol is preferable, and an ascorbic acid glycoside such as L-ascorbic acid glucoside Is more preferable.

  The blending amount of the water-soluble whitening component in the whitening external preparation of the present invention is not particularly limited, but is usually 0.1 to 20% by weight based on the total weight of the whitening external preparation, preferably It is 0.5 to 15 weight%, More preferably, it is 1 to 10 weight%.

  The whitening external preparation and the water-soluble whitening component skin penetration enhancer of the present invention may or may not contain a water-soluble polymer compound. Water-soluble polymers here include natural polymer compounds (polysaccharides, proteins, etc.) derived from plants, microorganisms, animals, semi-synthetic polymer compounds (cellulose-based, starch-based, alginic acid-based, etc.) and synthetic polymers. Classified into compounds (acrylic, vinyl, etc.). Furthermore, it can be divided into anionic, cationic, amphoteric and nonionic according to electrical properties. These water-soluble polymer compounds have various functions such as improvement of rheological properties (thickening action and the like), surface active action, film forming action, moisturizing action and inclusion action. Examples of natural polymer compounds include gum arabic, carrageenan, guar gum, roast bean gum, pectin, tragacanth, starch, xanthan gum, dextrin, fructan, pullulan, sodium hyaluronate, sodium chondroitin sulfate, gelatin, casein, etc. Protein. Examples of the cellulose semisynthetic polymer compound include ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, nitrocellulose, and cationized cellulose. Examples of the alginic acid semisynthetic polymer compound include sodium alginate and propylene glycol alginate. Examples of the acrylic synthetic polymer compound include sodium polyacrylate, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, polyacrylic acid amide, acrylamide / acrylic acid copolymer, and the like. Examples of vinyl-based synthetic polymer compounds include polyvinyl pyrrolidone and polyvinyl alcohol. Other examples include polyethylene glycol, polyglycerin, cationized guar gum, and polymethacryloyloxyethyl phosphorylcholine. Furthermore, derivatives of these polymer compounds, or copolymers of these polymer compounds and appropriate monomers, such as water-soluble ones can be mentioned. Among these compounds, taking into account the skin protective effect, skin flesh, transparency and smoothness, polysaccharide compounds, polymethacryloyloxyethyl phosphorylcholine and polymethacryloyloxyethyl phosphorylcholine and other monomers Coalescence is preferred.

  When the external preparation for whitening and the skin penetration enhancer of the water-soluble whitening component of the present invention contain a water-soluble polymer compound, the blending amount is 0.1 wt% to 3 wt%, 0.2 wt% to 2 wt%. %, 0.3 wt% to 1 wt% is more preferable.

  The external preparation for whitening and the skin penetration enhancer of the water-soluble whitening component of the present invention may further contain an aqueous medium. As the aqueous medium, water or an organic solvent miscible with water (normally water-miscible organic solvent) at normal temperature (25 ° C.) and a mixture of water can be used.

  Water may be aromatic distilled water such as cornflower water, and / or mineral water such as Vittel water, Lucas water, La Roche Posay water, and / or hot springs. It may be seawater such as water and / or deep seawater.

  The whitening external preparation of the present invention is in the range of 50 to 99.5 wt%, preferably in the range of 60 to 99 wt%, more preferably in the range of 70 to 95 wt%, based on the total weight of the whitening external preparation. Can contain water.

  The skin penetration enhancer of the water-soluble whitening component of the present invention is in the range of 0.1 to 30% by weight, preferably in the range of 1 to 20% by weight, more preferably 2 to 2%, based on the total weight of the skin penetration enhancer. Water can be included in the range of 10% by weight.

Examples of the organic solvent miscible with water at room temperature (25 ° C.) include the following.
Monoalcohols having 2 to 6 carbon atoms such as ethanol and isopropanol;
Polyols having 2 to 20 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, such as glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, di- Propylene glycol and diethylene glycol;
Glycol ethers (especially those having carbon atoms of 3 to 16), (e.g., mono -, di -, (C ₁ -C ₄₎ alkyl ethers of tripropylene glycol, and mono -, di -, tri (C ₁ -C ₄ ) alkyl ethers of ethylene glycol); and mixtures thereof.

  In the whitening external preparation of the present invention, the water-miscible organic solvent is 0.1 to 30% by weight, preferably 5 to 25% by weight, more preferably 10 to 20%, based on the total weight of the whitening external preparation. % By weight may be included.

  In the skin penetration enhancer of the water-soluble whitening component of the present invention, the water-miscible organic solvent is in the range of 0.1 to 30% by weight, preferably 1 to 20% by weight, based on the total weight of the skin penetration enhancer. And more preferably in the range of 2 to 10% by weight.

  Furthermore, the whitening external preparation of the present invention may contain a fragrance and / or vitamin E or a derivative thereof.

  As perfumes, natural or synthetic fragrances and aromas, and mixtures thereof can be used. According to a preferred embodiment of the present invention, various fragrances can be blended and used, thereby producing a fragrance generally favored by consumers.

  The blending amount of the fragrance in the whitening external preparation of the present invention is not particularly limited, but is usually 0.01 to 1% by weight, preferably 0.01 to 1% based on the total weight of the whitening external preparation. 0.5% by weight, more preferably 0.01 to 0.3% by weight.

  The derivative of vitamin E is not particularly limited, and examples thereof include tocopherol acetate.

  Although the compounding quantity of vitamin E or its derivative to the whitening external preparation of this invention is not specifically limited, 0.01-5 weight% is preferable on the basis of the total weight of a whitening external preparation.

  The whitening external preparation of the present invention is a topical composition applied to the surface of a human body for whitening, and is preferably a cosmetic or a skin external preparation. Here, the external preparation for skin should be applied onto the skin and can correspond to both dermatological drugs or quasi drugs. Here, “whitening” means any action that inhibits the production / deposition of melanin, and includes, for example, suppressing the production of melanin or reducing the produced melanin.

  The form of the cosmetic is not particularly limited, and may take any form such as a water-in-oil emulsified cosmetic, an oil-in-water emulsified cosmetic, an aqueous gel, an aqueous solution, and a multiple emulsion. The cosmetic may be either a skin cosmetic or a hair cosmetic, but is preferably a skin cosmetic. The whitening external preparation of the present invention is particularly suitable as a skin lotion or cosmetic liquid.

  When the whitening external preparation of the present invention is a lotion, the lotion is preferably transparent or uniform in appearance. Here, “transparent” means passing light without causing deflection due to refraction or reflection. The transparency of a composition such as lotion can be measured using a turbidimeter. The Hach portable turbidimeter model 2100P® can be used, for example, to measure the transparency limit of the composition. A composition is considered transparent when the measured turbidity is between 0 and 250 NTU.

  In addition to the above-mentioned components, the external agent for whitening of the present invention is an external agent, for example, components usually used in cosmetics, specifically acids, bases, salts, dyes, antioxidants, ultraviolet absorbers. , Blood circulation promoters, metal chelators, sebum suppressors, powders, astringents, skin softeners, moisturizers, surfactants, oils, organic solvents, silicones, silicone derivatives, natural extracts derived from animals and plants, waxes, etc. It can select suitably and use in the range which does not impair the effect of this invention.

  The whitening external preparation of the present invention, particularly a cosmetic, is used in a cosmetic treatment method including a step of applying to the skin. Therefore, the cosmetic treatment method is also a skin whitening method. This method is particularly suitable for removing stains due to brown pigments due to external factors and / or stains due to internal factors such as aging and / or for whitening brown skin.

  The skin penetration enhancer of the water-soluble whitening component of the present invention can be circulated as a product by itself and used in combination with the water-soluble whitening component. For example, the water-soluble whitening component skin penetration enhancer of the present invention is packaged in a predetermined manner and distributed on the market with the label of the water-soluble whitening component skin penetration enhancing agent. Therefore, the skin penetration enhancer of the water-soluble whitening component of the present invention can be used, for example, to add to an existing whitening cosmetic containing a water-soluble whitening component and enhance the whitening effect of the cosmetic. .

  Therefore, the skin permeation enhancer of the present invention is characterized by blending at least one alkylene oxide derivative represented by the above formula (I) into a whitening external preparation containing a water-soluble whitening component. It can be used suitably for the implementation of the method for enhancing the whitening of an external preparation for external use. In other words, the method is characterized by the use of at least one alkylene oxide derivative represented by the above formula (I) for enhancing the whitening property of the external preparation for whitening.

  In addition, the skin penetration enhancer of the present invention is characterized in that at least one alkylene oxide derivative represented by the above formula (I) is used in combination with a water-soluble whitening component, and the water-soluble whitening component penetrates into the skin. It can also be suitably used for carrying out the promotion method. In other words, the method is characterized by the use of at least one alkylene oxide derivative represented by the above formula (I) for promoting skin penetration of the water-soluble whitening component.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to an Example.

PEG/PPG/ホ゜リフ゛チレンク゛リコール-8/5/3 ク゛リセリン（ホ゜リオキシフ゛チレンホ゜リオキシエチレンホ゜リオキシフ゜ロヒ゜レンク゛リセロール）：
WILBRIDE S-753（日本油脂（株）） [Example 1 and Comparative Example 1]
The external preparations of Example 1 and Comparative Example 1 comprising the components shown in Table 1 below were prepared by the following method.

PEG / PPG / Polybutylglycol-8 / 5/3 Glycerin (Polyoxybutylene polyoxyethylene polyoxypropylene serol):
WILBRIDE S-753 (Nippon Yushi Co., Ltd.)

(1) Take a portion of phase B water and stir until homogeneous to dissolve ascorbyl glucoside.
(2) Dissolve sodium citrate and citric acid in the remaining phase B water and add to the aqueous ascorbyl glucoside solution obtained in (1). Next, potassium hydroxide is added and stirred until uniform.
(3) Mix Phase A ingredients, heat to 75 ° C., stir until uniform, then cool to room temperature.
(4) To the phase A obtained in (3), the mixed solution obtained in (2) is added and stirred.
(5) Add more phase C and stir.

[Skin penetration promotion evaluation]
The skin permeability of ascorbyl glucoside in the external preparations of Example 1 and Comparative Example 1 was evaluated as follows. The results are shown in Table 2.

(1) The external preparation of Example 1 is applied to any one of the forearms of 17 subjects, and the external preparation of Comparative Example 1 is applied to the other. It is random whether the external preparation of Example 1 and Comparative Example 1 is applied to the left or right arm.
(2) After 3 hours, the skin surfaces of the left and right arms are tape stripped 5 times (area 4 cm ² ) to obtain a stratum corneum sample.
(3) Using an LCUV & LC-Fluo apparatus, the abundance of ascorbyl glucoside in each sample is measured. Further, the abundance of tryptophan in each sample is separately measured in the same manner, and the ratio of the abundance of ascorbyl glucoside to the abundance of tryptophan is calculated.
(4) Calculate the average value of the stratum corneum sample for 5 times of tape stripping.

  From the results in Table 2, it can be seen that Example 1 has less ascorbyl glucoside remaining in the stratum corneum on the skin surface than Comparative Example 1. This indicates that the ascorbyl glucoside contained in Example 1 permeated more through the stratum corneum of the skin than Comparative Example 1.

Ascorbyl glucoside decreased by 26% on average in Example 1 than in Comparative Example 1 per unit area (cm ² ) of the stratum corneum sample. This difference was significant at less than 5% in statistical processing by Wilcoxon's non-parametric test method.

  On the other hand, when the amount of ascorbyl glucoside is normalized with respect to the amount of tryptophan, which is one of NMF (natural moisturizing factor) originally present in the skin stratum corneum, more accurate results can be obtained. In Example 1, ascorbyl glucoside was reduced by 37% on average in comparison with Comparative Example 1. This difference was significant at less than 5% in statistical processing by Wilcoxon's non-parametric test method.

Claims (6)

An external preparation for whitening comprising (a) PEG / PPG / polybutylene glycol-8 / 5/3 glycerin, and (b) at least one water-soluble whitening component. The external preparation according to claim 1, wherein the water-soluble whitening component is ascorbic acid or a derivative thereof. The external preparation according to claim 1 or 2, which is a cosmetic or an external preparation for skin. A skin penetration enhancer of a water-soluble whitening component comprising PEG / PPG / polybutylene glycol-8 / 5/3 glycerin. The skin penetration enhancer according to claim 4, wherein the water-soluble whitening component is ascorbic acid or a derivative thereof. A skin whitening method comprising applying the whitening external preparation according to any one of claims 1 to 3 to the skin.