JP2005119991A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation used for the skins and containing a tocotrienol derivative or its salt which has an excellent bleaching effect and can widely be compounded in preparations. <P>SOLUTION: This external preparation used for the skins and containing a tocotrienol derivative carboxylate represented by general formula (1) (R<SP>2</SP>is a nitrogen-substituted group-having carboxylic acid residue; R<SP>1</SP>and R<SP>3</SP>are each H or methyl) or its salt. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a skin external preparation containing a novel tocotrienol derivative or a salt thereof.

Conventionally, many cosmetics having a whitening effect are known, and a vitamin preparation is used as an active ingredient thereof. Among vitamin Es, cosmetics containing tocotrienol as one of the ingredients are disclosed (see Patent Document 1). However, tocotrienols are oily compounds that do not dissolve in water at all, so the dosage forms that can be blended are limited. On the other hand, a tocotrienol derivative having high solubility in water has been proposed (Patent Document 2). However, Patent Document 2 describes that this compound is hydrolyzed in vivo to release tocotrienol, but there is no description about the medicinal effect exhibited by this compound itself, and the effectiveness of an external preparation for skin is not described. There is no description at all about whether or not it shows a medicinal effect as an ingredient.
JP-A-8-92062 JP 2002-80475 A

  The present invention provides a medicinal agent such as a whitening agent composed of a compound having a specific structure that is highly soluble in water and highly safe, and by using such a medicinal agent, skin exhibiting good medicinal effects It is an object to provide an external preparation, particularly a skin external preparation excellent in whitening effect.

  As a result of intensive studies to solve the above problems, the present inventors have found that a tocotrienol derivative having a specific structure or a salt thereof can be widely mixed in a preparation and exhibits an excellent whitening effect. The present invention has been completed.

  That is, the present invention solves the above-mentioned problems by the following general formula (1):

(Wherein R ² represents a carboxylic acid residue having a nitrogen substituent, and R ¹ and R ³ each represent a hydrogen atom or a methyl group) or a carboxylic acid ester of tocotrienol represented by A skin external preparation containing a salt is provided.

  In one embodiment of the present invention, the carboxylic acid residue having a nitrogen substituent is a residue of an amino acid, an N-acyl amino acid, an N-alkyl amino acid, an N, N-dialkyl amino acid, a pyridinecarboxylic acid, or a salt thereof. Provided is a skin external preparation containing the above-mentioned external preparation for skin which is a carboxylic acid residue selected from the group; and a carboxylic acid ester of tocotrienol or a salt thereof as a whitening agent.

  From another viewpoint, a whitening agent comprising a carboxylic acid ester of tocotrienol represented by the general formula (1) or a salt thereof according to the present invention; a carboxylic acid ester of tocotrienol represented by the general formula (1) or A melanin production inhibitor comprising the salt; a method of using the tocotrienol carboxylic acid ester represented by the general formula (1) or a whitening agent comprising the salt; and a compound represented by the general formula (1) or A method of using the salt as a melanin production inhibitor is provided.

  Since the tocotrienol carboxylic acid ester represented by the general formula (1) or a salt thereof is highly water-soluble and exhibits an inhibitory effect on melanin production, it can be used for external preparations for skin, such as cosmetics, quasi-drugs, and pharmaceuticals. It is useful as a whitening component that can be incorporated into a wide range of preparations, and the skin external preparation of the present invention containing this is excellent in whitening effect.

Hereinafter, preferred embodiments of the present invention will be described.
The present invention relates to an external preparation for skin containing a carboxylic acid ester of tocotrienol represented by the following general formula (1) or a salt thereof. The carboxylic acid ester of tocotrienol represented by the following general formula (1) can be contained alone in a skin external preparation, or can be blended in the skin external preparation as a salt thereof.

In the formula, R ¹ and R ³ each represent a methyl group, and R ² represents a carboxylic acid residue having a nitrogen substituent. In general, the carboxylic acid residue is represented by —C (═O) —R (R is a substituent). The carboxylic acid residue having a nitrogen substituent means that R in the above formula contains at least a nitrogen substituent, and R may be a nitrogen substituent (for example, an amino group). The nitrogen substituent may be a chain group or a cyclic group. Preferable specific examples include an unsubstituted amino group, an amino group substituted with 1 or 2 alkyl groups or an acyl group, and a pyridyl group. A substituted or unsubstituted amino group is preferred. As the alkyl group of the alkyl-substituted amino group, a linear or branched alkyl group having 1 to 6 carbon atoms such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, and an n-hexyl group. , An isopropyl group, an isobutyl group, a 1-methylpropyl group, a tert-butyl group, a 1-ethylpropyl group, an isoamyl group, and the like, and a methyl group and an ethyl group are particularly preferable. The acyl group of the acyl-substituted amino group is preferably an acyl group having a hydrocarbon chain of a linear or branched alkyl group having 1 to 6 carbon atoms, and specific examples of the alkyl group moiety are as described above.

  The carboxylic acid residue may contain a linking group that links both the carbonyl group and the nitrogen substituent. The linking group is preferably a linear, branched or cyclic alkylene group having 1 to 7 carbon atoms. The branched alkylene group means an alkylene group derived from an alkyl group such as isopropyl, isobutyl, tert-butyl, 1-ethylpropyl and the like. The cyclic alkylene group means an alkylene group containing a cyclopentane ring, a cyclohexane ring, a methylcyclohexane ring or the like in the structure. Particularly preferred as the alkylene group is a methylene group or an ethylene group.

  The carboxylic acid residue may have a substituent other than a nitrogen substituent. Examples of the substituent other than the nitrogen substituent include a carboxyl group, a hydroxyl group, and a thiol group. Examples of the carboxylic acid residue include amino acids, N-acyl amino acids, N-alkyl amino acids, N, N-dialkyl amino acids, amino acids having a hydroxyl group, a thiol group or a carboxyl group in the side chain, pyridine carboxylic acids, and these Salt residues are included.

  The nitrogen substituent in the carboxylic acid residue may form a salt, and for example, a hydrohalide, an alkyl sulfonate, and a saccharide are preferable. As the hydrohalide, hydrochloride, hydrobromide and the like are preferable. In the present invention, the hydrohalide salt is often crystallized or solidified, and has an advantage of easy handling during formulation. Examples of the alkyl sulfonate include methane sulfonate. In the case of this alkyl sulfonate, solidification with low hygroscopicity is possible. Examples of the saccharide salt include gluconate, glucoheptanoate, and lactobionate. Solidification is possible in the case of a saccharide salt.

Various methods for producing the compound represented by the general formula (1) are conceivable, and typical methods are described as follows. In the following formulae, R ^{1 to} R ³ have the same meanings as those in the general formula (1).

  By carrying out an esterification reaction by a conventional method with the tocotrienols represented by the general formula (2) and a carboxylic acid having a nitrogen substituent, or a reactive acid derivative thereof or a hydrohalide thereof, A compound represented by the formula (1) can be obtained. The esterification reaction of tocotrienols follows a conventional method. For example, the carboxylic acid residue is a carboxylic acid residue having a primary or secondary amino group, or a carboxylic acid residue of an amino acid having a hydroxyl group or thiol group in the side chain. In the case of producing a compound that is a group, an esterification reaction using such a reactive substituent (primary or secondary amino group, hydroxyl group or thiol group) protected with an appropriate protecting group as a reagent. Is preferably performed. As the protecting group, a tert-butoxycarbonyl group (hereinafter abbreviated as t-BOC group), a benzyloxycarbonyl group (hereinafter abbreviated as Z group) and the like are preferable. Thereafter, the desired compound can be produced by removing the protecting group as desired.

  In the case of producing a compound in which the carboxylic acid residue is a carboxylic acid residue of an N, N-dialkylamino acid, an active esterification reagent using a hydrohalide of N, N-dialkylamino acid as a reagent It is preferable to carry out the ester reaction in the presence of. Examples of the active esterification reagent include dicyclohexylcarbodiimide (hereinafter abbreviated as DCC), N, N-disuccinimide oxalate (hereinafter abbreviated as DSO), and the like. In this case, anhydrous pyridine is preferred as the solvent. It is also preferable to carry out the esterification reaction using a reactive acid derivative of N, N-dialkylamino acid as a reagent. Acid halogenites, especially those using acid chloride, give favorable results. In this case, an anhydrous benzene / anhydrous pyridine mixture is preferred as the solvent.

  By reacting a free tocotrienol carboxylic acid ester obtained by the above method with a hydrolactone, alkyl sulfonic acid or acidic sugar lactone in a conventional manner, a hydrohalide, alkyl sulfonate, or Saccharate can be produced. Moreover, after manufacturing N-acyl amino acid ester, a hydrohalide can be manufactured by deprotecting with a hydrohalic acid by a conventional method.

  In addition, the carboxylic acid ester of tocotrienol according to the present invention may be a bile salt. Here, the bile salt specifically refers to salts of taurocholic acid, glycocholic acid, cholic acid, taurodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, ursodeoxycholic acid, and the like. . And a bile salt can be obtained by making the said tocotrienol carboxylic acid ester react with these bile acids. For example, a tocotrienol carboxylate bile salt can be obtained by using a lower alcohol solvent such as methanol, ethanol or propanol and distilling off the solvent under reduced pressure after completion of the reaction.

The carboxylic acid ester of tocotrienol represented by the above general formula (1) of the present invention or a salt thereof is an excellent whitening agent exhibiting a remarkable inhibitory action in a melanin production inhibition test using B-16 melanoma cells. Moreover, the said compound or its salt is high in water solubility, and it is easy to mix | blend with an aqueous skin external preparation. As a result, it is not necessary to separately add an additive such as a surfactant to solubilize the compound or a salt thereof, which is advantageous in terms of formulation and safety.
In the present specification, the “whitening effect” does not mean only an inhibitory effect on melanin production, but, for example, suppression of pigmentation, skin dullness, prevention and improvement of skin darkening due to sunburn, etc. It is necessary to interpret in the broadest sense including the effects of.

  The skin external preparation of this invention contains the compound or its salt represented by the said General formula (1). The content is preferably 0.00001 to 1% by mass (hereinafter simply referred to as “%”), and more preferably 0.0001 to 0.1%. If it exists in this range, it can mix | blend stably and can show the outstanding medicinal effect.

  Examples of the formulation of the external preparation for skin of the present invention are not particularly limited. For example, emulsions, creams, lotions, cosmetics, packs, cleaning products, makeup cosmetics, dispersions, ointments, solutions, aerosols, patches Any form of cosmetics such as pills, poultices, liniments and the like may be external medicines.

  The topical skin preparation of the present invention contains components that are usually used in preparations such as cosmetics, quasi-drugs, and external pharmaceuticals, that is, water (purified water), as long as the effects of the present invention are not impaired as necessary. , Hot spring water, deep water, etc.), alcohol, oil agent, surfactant, metal soap, gelling agent, powder, alcohol, water-soluble polymer, film-forming agent, resin, UV protection agent, inclusion compound, antibacterial Agent, fragrance, deodorant, salt, pH adjuster, refresher, animal / microbe-derived extract, plant extract, blood circulation promoter, astringent, antiseborrheic agent, whitening agent, anti-inflammatory agent, active oxygen scavenger Agents, cell activators, humectants, chelating agents, keratolytic agents, enzymes, hormones, vitamins and the like can be added. By combining with these drugs, it can be expected to exhibit more excellent effects. Specific examples of suitable components include those shown below. Here, “derivatives” include salts that can be formed.

  Alcohols include lower alcohols such as ethanol, glycerin, diglycerin, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene for the purposes of dissolution, refreshment, antiseptic, moisturizing and the like. Polyhydric alcohols such as glycol can be used.

As an oil agent, it is a natural oil, a synthetic oil, or a solid oil as long as it is used for normal cosmetics as a constituent component or usability of the base, improving the feeling of use. Regardless of properties such as semi-solid or liquid, hydrocarbons, waxes, fatty acids, higher alcohols, ester oils, silicone oils, fluorine oils and the like can be used.
For example, hydrocarbons such as squalane and petrolatum; olive oil, castor oil, mink oil, macadamia nut oil, apricot oil, persic oil, safflower oil, sunflower oil, avocado oil, medhome oil, camellia oil, almond oil, Oils derived from plants and animals such as sesame oil, sesame oil, borage oil, and shea fat; ester oils such as cetyl isostearcetylate, diglyceryl isostearate and jojoba oil; and waxes such as beeswax, carnauba wax, candelilla wax, and gay wax And the like.

  Examples of UV protection agents include para-methoxycinnamate-2-ethylhexyl, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5 sodium sulfate, 4-t-butyl-4′-methoxydi Examples include benzoylmethane, 2-phenyl-benzimidazole-5-sulfuric acid, titanium oxide, and zinc oxide.

  The water-soluble polymer is used for stabilizing the system, improving the usability and the feeling of use, and is also used for obtaining a moisturizing effect. Specific examples of water-soluble polymers include plant polymers such as carrageenan, pectin, agar, locust bean gum, microbial polymers such as xanthan gum, animal polymers such as casein and gelatin, and starch polymers such as starch. And cellulose polymers such as methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, and crystalline cellulose, alginic acid polymers such as sodium alginate, vinyl polymers such as carboxyvinyl polymer, and the like.

  Examples of the antibacterial agent include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol and the like.

  The whitening agent is used for the purpose of preventing skin darkening caused by sunburn, etc., stains caused by pigmentation, freckles, etc., vitamin C and its derivatives, placenta extract, licorice extract, age extract, ougon extract , Seaweed extract, cucumber extract, caquette extract, gokahi extract, rice bran extract, wheat germ extract, saicin extract, hawthorn extract, sun penz extract, shirayuri extract, peony extract, sempukuka extract , Soybean extract, tea extract, molasses extract, juniper extract, grape extract, hop extract, mica squid extract, mokka extract, yukinoshita extract, yokuinin extract and the like.

  Anti-inflammatory agents are used for the purpose of suppressing inflammation such as hot flashes and erythema on the skin after sunburn. Sulfur and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, aloe extract, Altea extract, Ashitaba Extract, Arnica extract, Ginseng extract, Nettle extract, Duckweed extract, Hypericum extract, Chamomile extract, Snapdragon extract, Watercress extract, Comfrey extract, Salvia extract, Shikon extract, Perilla extract Product, birch extract, gentian extract and the like.

  The cell activator is used for the purpose of improving rough skin, etc., such as caffeine, chicken crown extract, shell extract, shell extract, royal jelly, silk protein and its degradation product or derivative thereof, lactoferrin or its degradation product, Mucopolysaccharides such as chondroitin sulfate and hyaluronic acid or their salts, collagen, yeast extract, lactic acid bacteria extract, bifidobacteria extract, fermentation metabolic extract, ginkgo biloba extract, barley extract, assembly extract, tiso extract , Carrot extract, rosemary extract, glycolic acid, citric acid, lactic acid, malic acid, tartaric acid, organic acids such as succinic acid, and derivatives thereof.

  The active oxygen scavenger is used for the purpose of suppressing oxidative damage such as lipid peroxide production suppression, superoxide dismutase, mannitol, quercetin, catechin and its derivatives, rutin and its derivatives, button pi extract, yashajtsu extract, melissa extract Products, rahan fruit extract, retinol and derivatives thereof, vitamin A such as carotenoid, thiamine and derivatives thereof, riboflavin and derivatives thereof, pyridoxine and derivatives thereof, vitamin B such as nicotinic acid and derivatives thereof, tocopherol and derivatives thereof, etc. Vitamin E, dibutylhydroxytoluene, butylhydroxyanisole, etc. are mentioned.

  As the humectant, proteins such as elastin and keratin or derivatives thereof, hydrolysates and salts thereof, amino acids such as glycine, serine, aspartic acid, glutamic acid, arginine and theanine and derivatives thereof, sorbitol, erythritol, trehalose, Inositol, glucose, sucrose and derivatives thereof, dextrin and derivatives thereof, saccharides such as honey, D-panthenol and derivatives thereof, urea, phospholipid, ceramide, auren extract, shobu extract, dio extract, senkyu extract, Examples of this include mallow mushroom extract, periwinkle extract, dokudami extract, hamamelis extract, bodaiju extract, maronier extract, quince extract and the like.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples.
[Synthesis example]
The tocotrienol derivatives shown in Table 1 and Table 3 were produced by any one of the following production methods A to D. Table 2 shows the measurement results of 1H-NMR spectrum of the compounds shown in Table 1.

<< Production Method A >>
0.1 mol of amino acid (for example, glycine is used when producing compound No. 1 in Table 1) is dissolved in 100 mL of distilled water-dioxane (1: 1, v / v), 30 mL of triethylamine is added, and Di-tert-butyl dicarbonate is added slowly and stirred for 30 minutes at room temperature. Dioxane is distilled off under reduced pressure, and 50 mL of an aqueous sodium hydrogen carbonate solution (0.5 M) is added, followed by washing with 100 mL of ethyl acetate. The ethyl acetate layer was washed with 50 mL of sodium hydrogen carbonate solution, and the aqueous layers were combined and acidified (pH 3) by adding an aqueous citric acid solution (0.5 M) under ice cooling. After saturating sodium chloride, Extract (3 x 100 mL). After dehydrating the extract with anhydrous sodium sulfate, the solvent is distilled off under reduced pressure, and isopropyl ether is added to the oily residue or crystallized by cooling to obtain an Nt-BOC amino acid.

  Under an argon gas atmosphere, 5 mmol of tocotrienol, 5 mmol of Nt-BOC amino acid and 5 mmol of DCC are added to 30 mL of anhydrous pyridine and stirred at room temperature for 20 hours. The solvent is distilled off under reduced pressure, and ethyl acetate is added to the residue to extract a soluble fraction (100 mL × 2 times). The extract is concentrated under reduced pressure, and the residue is separated and purified by silica gel column chromatography (eluent: n-hexane-ethyl acetate = 9: 1) to obtain tocotrienol Nt-BOC-amino acid ester.

  Tocotrienol Nt-BOC-amino acid ester was dissolved in a small amount of acetone, hydrochloric acid-dioxane (2.5-4.0N) was added in an amount corresponding to 20 times the molar amount of hydrochloric acid, and the mixture was stirred for 1 hour. The solvent is distilled off under reduced pressure. The residue is recrystallized with an acetone-methanol system or an ethyl acetate-methanol system to obtain a hydrochloride of tocotrienol amino acid.

<< Production Method B >>
Tocotrienol amino acid hydrochloride (3 mmol) is added to 150 mL of water, and sodium bicarbonate is added to adjust the pH of the solution to 7 to 8, followed by extraction with ethyl acetate (3 × 100 mL). The extract is dehydrated with anhydrous sodium sulfate and the solvent is distilled off under reduced pressure to obtain an oily tocotrienol amino acid.

<< Production Method C >>
Under an argon gas atmosphere, 5 mmol of tocotrienol, 5 mmol of N, N-dialkylamino acid hydrochloride (for example, N, N-dimethylglycine is used when producing compound No. 17 in Table 3) and 5 mmol of DCC are added to 30 mL of anhydrous pyridine. Add and stir at room temperature for 20 hours. The solvent is distilled off under reduced pressure, the residue is suspended in distilled water, sodium hydrogen carbonate is added to adjust the pH of the solution to 7-8, and then extracted with ethyl acetate (100 mL × 3 times). The extract was dehydrated with anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent: n-hexane-ethyl acetate = 8: 2), and tocotrienol N, N-dialkylamino acid was obtained. Get.

<< Production Method D >>
Tocotrienol amino acid or tocotrienol N, N-dialkylamino acid (2 mmol) is dissolved in acetone (20 mL), and hydrochloric acid-dioxane (2.5-4.0 N) is added in an amount corresponding to 10-fold molar amount of hydrochloric acid, or 2 mmol of alkylsulfonic acid. And the solvent is distilled off under reduced pressure. The residue is recrystallized with an acetone-methanol system or an ethyl acetate-methanol system to obtain a hydrochloride of tocotrienol amino acid or tocotrienol N, N-dialkylamino acid.

  Specific chemical formulas, physical properties and production methods of the synthesized compounds are shown below. In Table 1, Compound No. About 1-7, the result of having measured mass spectrometry (m / z, FAB-MS) and a nuclear magnetic resonance spectrum (1H-NMR, (delta) ppm, internal standard TMS) is shown in Table 2.

The synthesized compound No. 5 and no. The melanin production inhibitory effect with respect to the cultured pigment cell of the sample (Sample 1 and 2) containing each of 6 was evaluated as follows.
[Example 1: Inhibition test of melanin production by cultured cells]
The cultured cells were mouse-derived B-16 melanoma cells. Only purified aqueous solutions and purified water of the compounds produced in the above synthesis examples were used as samples added to the medium. The medium was changed halfway, and after culturing for 5 days, the cells were collected, the number of cells was measured, and intracellular melanin was quantified. Similarly, the amount of melanin at the concentration of each sample was quantified by setting the amount of melanin when purified water was added in place of the sample as 100%, and was defined as the melanin production rate (%).
In order to evaluate the melanin production inhibitory effect of the sample, IC50 was introduced as an evaluation standard. Specifically, the sample concentration IC50 (melanin production rate) at which the melanin production rate was 50% was determined. The smaller the value of IC50 (melanin production rate), the higher the melanin production inhibitory effect.

  As Comparative Sample 1, L-ascorbic acid magnesium phosphate, which is a water-soluble compound that is generally known to have a melanin production inhibitory effect, was used for the same test as described above. Table 4 shows IC50 (melanin production rate) obtained for Samples 1 and 2 of the present invention and Comparative Sample 1.

  From the results shown in Table 4, it was clarified that Samples 1 and 2 of the present invention were much more excellent in the melanin production inhibitory effect than Comparative Sample 1. From the above, it was clarified that the product of the present invention is remarkably superior in whitening effect as compared with the conventional water-soluble whitening agent.

Examples of the external preparation for skin containing the compound of the general formula (1) synthesized in the above synthesis examples will be shown below.
[Example 2: lotion]
A solution in which the following components (3) to (5) and (9) to (11) are mixed and dissolved, and a solution in which (1), (2), (6) to (8) and (12) are mixed and dissolved The mixture was made uniform to obtain a lotion.
(Prescription) (%)
(1) Glycerin 5.0
(2) 1,3-butylene glycol 6.5
(3) Polyoxyethylene (20E.O.) sorbitan 1.2
Monolaurate (4) Ethyl alcohol 8.0
(5) Compound No. 5 0.005
(6) Magnesium L-ascorbate phosphate * 1 0.5
(7) Lactic acid 0.05
(8) Sodium lactate 0.1
(9) Paramethoxycinnamic acid-2-ethylhexyl 3.0
(10) Preservative appropriate amount (11) perfume appropriate amount (12) remaining amount of purified water * 1 Sigma

[Example 3: Latex]
The following components (1) to (6), (8) and (9) were heated and mixed, and the mixture maintained at 70 ° C was heated and mixed with components (12), (13) and (16) to 70 ° C. In addition to the maintained mixture, mixed and uniformly emulsified. After the mixture was cooled, the mixture of components (7), (10) and (15) was added and mixed uniformly. Component (11) was added to this mixture and stirred sufficiently, and components (14) and (17) were further added and mixed uniformly to obtain an emulsion.
(Prescription) (%)
(1) Polyoxyethylene (10E.O.) sorbitan 1.0
Monostearate (2) Polyoxyethylene (60EO) Sorbit 0.5
Tetraoleate (3) Glyceryl monostearate 1.0
(4) Stearic acid 0.5
(5) Behenyl alcohol 0.5
(6) Squalane 8.0
(7) Retinol palmitate * 1 0.002
(8) Dipotassium glycyrrhizinate * 2 0.3
(9) Compound No. 6 0.02
(10) Daylily extract * 3 0.1
(11) Hyaluronic acid 0.1
(12) Preservative 0.1
(13) Carboxyvinyl polymer 0.1
(14) Sodium hydroxide 0.05
(15) Ethyl alcohol 5.0
(16) Purified water remaining amount (17) Fragrance appropriate amount * 1 Made by Nippon Roche * 2 Made by Sigma * 3 Made by Maruzen Pharmaceutical Co., Ltd.

The lotion of Example 2 and the emulsion of Example 3 were both highly stable and excellent in the whitening effect.

Claims (3)

The following general formula (1):

(Wherein R ² represents a carboxylic acid residue having a nitrogen substituent, and R ¹ and R ³ each represent a hydrogen atom or a methyl group) or a carboxylic acid ester of tocotrienol represented by An external preparation for skin containing salt. The carboxylic acid residue having the nitrogen substituent is selected from the group consisting of amino acid, N-acyl amino acid, N-alkyl amino acid, N, N-dialkyl amino acid, pyridine carboxylic acid and salts thereof. The skin external preparation according to claim 1, which is a residue. The skin external preparation of Claim 1 or 2 which contains the said compound as a whitening agent.