JP2006265140A - Skin whitening agent, external preparation for skin-whitening and method for skin-whitening - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin-whitening agent that effectively suppress the formation of melanin, prevents and improves the deposition of pigment after sunburn, flecks, age spots, liver spots and the like with high safety and provide an external preparation for skin-whitening including the skin-whitening agent. <P>SOLUTION: The agent comprises one or two or more kinds selected from tranexamic acid and its derivatives; alkoxysalicylic acid and its salts; and one or two or more kinds selected from α-lipoic acid and its derivatives and their salts. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a skin whitening external preparation that suppresses the production of melanin and is effective in preventing and improving pigmentation, stains, freckles, liver spots and the like after sunburn.

Skin pigmentations range from cosmetics such as spots and freckles, to those found in skin diseases such as liver spots and sparrow eggs. Although there are many unclear points in the mechanism of action of these pigment abnormalities, in general, melanin pigments are formed by stimulation of hormonal abnormalities, ultraviolet rays from sunlight, etc., which are abnormally deposited in the skin It is believed that. For the treatment of such pigment abnormalities, melanin inhibitory substances are used as symptomatic treatments. For example, a method of orally administering vitamin C, a method of injecting glutathione, or the like, kojic acid, vitamin C and A method of locally applying the derivative, cysteine or the like in the form of an ointment, cream, lotion or the like is used. However, these methods are not yet effective enough.
On the other hand, recently, hydroquinone and its derivatives, which are melanin production inhibitors, have been developed (see Patent Document 1) and used as pharmaceuticals for the purpose of depigmentation of pigment spots.

JP 60-56912 A

  However, the hydroquinone derivative has an extremely slow effect and its whitening effect is not sufficient. In addition, although hydroquinone itself has been recognized for its whitening effect, its use is restricted due to safety issues. Derivatives that reduce the side effects of this hydroquinone and have an excellent whitening effect have been studied, but those having sufficient effects and safety have not yet been obtained. The present invention has been made in view of the above technical problems, and an object thereof is to provide a whitening agent having an excellent whitening effect and high safety, and a skin whitening agent for whitening using the same.

  As a result of intensive studies to solve the problems of the prior art, the present inventors have found that one or more selected from tranexamic acid and its derivatives, alkoxysalicylic acid and its salts, α-lipoic acid and its By using one or more selected from derivatives and pharmacologically acceptable salts thereof, a whitening agent whose whitening effect is synergistically enhanced can be obtained, and by using the whitening agent Thus, the present inventors have found that a skin whitening preparation for whitening which is stable and does not have safety problems such as skin irritation and skin sensitization can be obtained, and the present invention has been completed.

  That is, the present invention comprises one or more selected from tranexamic acid and derivatives thereof, alkoxysalicylic acid and salts thereof, and one or more selected from α-lipoic acid and derivatives and salts thereof. A whitening agent characterized by the above, and a skin whitening external preparation containing the same. In the present invention, the salt refers to a pharmacologically acceptable salt.

  Furthermore, according to this invention, the whitening method characterized by performing whitening of skin using the above-mentioned whitening agent is provided.

  With respect to tranexamic acid and its salts, the detailed mechanism of action of the anti-pigmentation effect is unknown, but it is known to have a whitening effect (JP-A-1-93519). Alkoxysalicylic acid and its salts are also known to have a whitening effect due to a melanin production-inhibiting action based on tyrosinase inhibition (JP-A-6-40886). Further, α-lipoic acid is also known to have a whitening effect due to a melanin production inhibitory action based on a tyrosinase inhibitory effect (Japanese Patent Laid-Open No. 63-8315).

  However, it has not been suggested at all that a whitening agent having a whitening effect that has never been obtained can be obtained by using tranexamic acids or alkoxysalicylic acids in combination with α-lipoic acids.

  Surprisingly, when these different active ingredients are blended, a synergistic effect exceeding each effect can be obtained as described later, not just an additive effect obtained by adding two effects. The mechanism of action is not clear, but it is considered that a complementary action in which the other part complements a part that cannot be covered by one action mechanism or some correlation action occurs.

The whitening agent of the present invention has an excellent whitening effect and is highly safe.
Moreover, the skin external preparation for whitening of this invention is excellent in the whitening effect, is stable, and has no safety problems such as skin irritation and skin sensitization.

Hereinafter, the configuration of the present invention will be described in detail.
Examples of the tranexamic acid derivative used in the present invention include a dimer of tranexamic acid (for example, trans-4- (transaminomethylcyclohexanecarbonyl) 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-aminomethylcyclohexanecarbonyloxy-5-hydroxybenzoic acid) Acid and its salts), amides of tranexamic acid (for example, trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salts, trans-4- (P-methoxyvinzoyl) aminomethylcyclohexanecarboxylic acid and And salts thereof, trans-4-guanidinoaminomethylcyclohexanecarboxylic acid, and salts thereof).

  The alkoxysalicylic acid used in the present invention is one in which the hydrogen atom at the 3-position, 4-position or 5-position of salicylic acid is substituted with an alkoxy group, and the alkoxy group as the substituent is preferably a methoxy group, ethoxy group Group, propoxy group, isopropoxy group, butoxy group, 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.
The alkoxysalicylic acid can be converted into a salt by a known method, and the salt is not particularly limited. For example, an alkali metal salt or alkaline earth metal salt such as sodium salt, potassium salt, calcium salt is used. In addition, salts such as ammonium salts and amino acid salts can be mentioned.

  Examples of the derivatives of α-lipoic acid used in the present invention include lipoic acid alkyl ester, alkenyl ester, amide, dihydrolipoic acid, dihydrolipoamide and the like. The salt of α-lipoic acid is not particularly limited, and examples thereof include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt and calcium salt, and salts such as ammonium salt and amino acid salt. .

  The whitening agent of the present invention is a combination of the above tranexamic acid or alkoxysalicylic acid (1) and α-lipoic acid (2), and the optimal combination ratio thereof is (1): (2) = 1: 1000 to 1000: 1 (mass ratio), more preferably 1: 100 to 100: 1.

  The skin whitening preparation for whitening according to the present invention is formed by blending the above-described whitening agent of the present invention. When a salt of alkoxysalicylic acid or a salt of α-lipoic acid and its derivative is blended, these may be blended directly in the form of a salt, or a free acid and a base are blended to form a salt in the system. It may be made to become.

  In order to obtain an effective whitening effect in the whitening skin external preparation of the present invention, the amount of one or more selected from tranexamic acid and derivatives thereof, alkoxysalicylic acid and salts thereof is based on the total amount of skin external preparation Preferably it is 0.001-20 mass%, More preferably, it is 0.01-10 mass%. If the blending amount is less than 0.001% by mass, the whitening effect is poor, and if it exceeds 20% by mass, the whitening effect reaches its peak and no increase in effect commensurate with the increase in the blending amount is observed.

  In order to obtain an effective whitening effect in the skin external preparation of the present invention, the amount of one or more selected from α-lipoic acid and its derivatives and salts thereof is preferably 0 with respect to the total amount of the skin external preparation. 0.001 to 20% by mass, and more preferably 0.01 to 10% by mass. If the blending amount is less than 0.001% by mass, the whitening effect is poor, and if it exceeds 20% by mass, the whitening effect reaches its peak and no increase in effect commensurate with the increase in the blending amount is observed.

  In addition to the above-mentioned essential components, the skin whitening external preparation for whitening of the present invention is usually used in skin external preparations such as cosmetics and pharmaceuticals, as long as the effects of the present invention are not impaired. Whitening agents, moisturizers, antioxidants, oily ingredients, UV absorbers, surfactants, thickeners, alcohols, powder ingredients, coloring materials, aqueous ingredients, water, various skin nutrients, etc. as required It can mix | blend suitably and can be manufactured by a conventional method.

  The skin whitening external preparation of the present invention means an external preparation applied to the skin for the purpose of whitening, and as cosmetics, pharmaceuticals, quasi drugs, for example, ointments, creams, emulsions, lotions, packs, foundations, It can be used in the form of a product such as a bath agent, and the dosage form is not particularly limited.

  Next, the present invention will be described in more detail with reference to examples. In addition, this invention is not limited only to these Examples. All compounding amounts are mass%.

First, the test method relating to the whitening effect, that is, the effect of improving pigmentation symptoms, as referred to in the present invention will be described.
The effect of improving pigmentation symptoms is a group of 10 female panels having pigmentation symptoms such as remarkable spots and freckles. Among the following examples (described in Table 1) or comparative examples (described in Table 2) Any one of them was used twice a day for 3 months, and the state of pigmentation after 3 months was observed and evaluated in comparison with before use. The improved state of pigmentation was evaluated according to the criteria shown in Table 3, and the average score of 10 people was calculated. The results are shown in Table 4.

Examples 1-4 Beauty liquid (1) 1,3-butylene glycol 80.0 mass%
(2) α-Lipoic acid 0.1
(3) Purified water Residue (4) Components shown in Table 1 and blending amounts (production method): Components (1) to (4) are mixed and homogenized.

Comparative Examples 1 to 10 Essence (1) 1,3-butylene glycol 80.0% by mass
(2) Purified water Residual (3) Components shown in Table 2 and blending amounts (production method): Components (1) to (3) are mixed and homogenized.

  As is clear from Table 4, in the example use group according to the present invention, marked improvement in pigmentation symptoms was observed in all groups. On the other hand, in the comparative example blended with the whitening agent alone, although improvement of the pigmentation symptom was observed, the degree of improvement was small compared with the working group. Moreover, it turned out that the whitening effect with respect to the working group 1-4 use group is clearly superior to what added the effect with respect to the corresponding comparative example 1-4 use group and the comparative example 5 use group. Moreover, it turned out that it is clearly superior to what added the effect with respect to the corresponding comparative example 6-9 use group and comparative example 10 use group whose density | concentration becomes 10 times.

  In Examples 1 to 4 of the present invention, no change in the state of the preparation such as precipitation, separation, aggregation, odor change, and discoloration of the components was observed during the test period. Moreover, in each Example use group, the panel which showed skin irritation reactivity and skin sensitization reaction did not exist.

Examples of other skin whitening agents for whitening in the present invention are shown below. All are manufactured by a conventional method.
Example 5 Cream (Whitening)
Trans-4- (Transaminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid 1.0% by mass
4-methoxysalicylate potassium 1.0
Sodium lipoate 1.0
Arbutin 1.0
Coenzyme Q10 (CoQ10) 0.03
Vaseline 2.0
Dimethylpolysiloxane 2.0
Ethanol 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 0.5
Jojoba oil 3.0
Squalane 2.0
Phytosteryl hydroxystearate 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 1.0
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide 0.1
Sodium pyrosulfite 0.01
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
Arbutin 7.0
Tranexamic acid 1.0
Tocopherol acetate 0.1
Sodium hyaluronate 0.05
P-Hydroxybenzoate appropriate amount trisodium edetate 0.05
4-t-butyl-4 '
-Methoxydibenzoylmethane 0.1
Diparamethoxycinnamic acid mono-2-ethylhexanoate glyceryl 0.1
Yellow iron oxide xanthane gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue

Example 6 Cream (Whitening)
Trans-4- (Transaminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid 1.0% by mass
Lipoamide 1.0
Ascorbyl-2-glucoside 1.0
Dimethylpolysiloxane 3.0
Decamethylcyclopentasiloxane 25.0
Trimethylsiloxysilicic acid 1.0
Polyoxyethylene / methylpolysiloxane copolymer 2.0
Glycerin 1.0
1,3-butylene glycol 5.0
Squalane 1.0
Titanium oxide 1.0
Talc 2.0
Aluminum stearate 0.5
Oil-soluble licorice extract 0.5
Edetic acid 3Na appropriate amount paraben appropriate amount phenoxyethanol appropriate amount dimethyl distearyl ammonium hectorite 0.8
Spherical nylon powder 1.0
Purified water residue

Example 7 Cream (Whitening)
3-Methoxysalicylic acid 1.0% by mass
Lipoamide 1.0
Ascorbic acid phosphate magnesium 1.0
Decamethylcyclopentasiloxane 30.0
Polyoxyethylene / methylpolysiloxane copolymer 1.5
Trimethylsiloxysilicate 0.5
Glycerin 2.0
Dipropylene glycol 5.0
Talc 5.0
Spherical silica 0.5
Palmitic acid dextrin coated fine particle titanium oxide (30 nm) 7.0
Spherical polyethylene powder 2.0
Poly (oxyethylene / oxypropylene)
・ Methylpolysiloxane copolymer 1.0
Paraben appropriate amount phenoxyethanol appropriate amount edetate trisodium 0.02
Dimethyl distearyl ammonium hectorite 0.5
Purified water residue

Example 8 Cream (Whitening)
Trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester 1.0% by mass
Lipoic acid ethyl ester 0.1
Oil-soluble licorice extract (root) 0.1
Methylphenylpolysiloxane 5.0
Stearyl alcohol 2.0
Glycerin 5.0
Dipropylene glycol 5.0
Sorbit liquid (70%) 5.0
Stearic acid 1.5
Palmitic acid 1.0
Tetra-2-ethylhexanoic acid pentaerythrit 4.0
Self-emulsifying glyceryl monostearate 1.0
Potassium hydroxide 0.15
Octyl methoxycinnamate 6.0
Vaseline 2.0
Tranexamic acid 2.0
1,3-butylene glycol 4.0
Squalane 3.0
Sodium citrate 0.1
Acetylated sodium hyaluronate 0.1
Xanthan gum 0.2
Bentonite 1.0
Paraben Appropriate amount Purified water Residual perfume Appropriate amount

Example 9 Cream (Whitening)
4-Ethoxysalicylic acid 1.0% by mass
Lipoic acid ethyl ester 0.1
Ougon extract (root) 0.1
Decamethylcyclopentasiloxane 35.0
Trimethylsiloxysilicate 0.5
Behenyl alcohol 1.0
Batyl alcohol 2.0
Glycerin 1.0
Dipropylene glycol 4.0
Plant-based squalane 3.0
Sara honey bee 1.0
Candelilla wax 0.5
Fine particle titanium oxide (30 nm) 5.0
Talc 4.0
Sodium hexametaphosphate 0.1
Xanthan gum 0.1
Porous cellulose powder 2.0
Bentonite 0.5
Sodium carboxymethylcellulose 0.05
Purified water residue

Example 10 Two-layer cream (sunscreen)
Tranexamic acid 1.0% by mass
Lipoic acid 1.0
4-methoxysalicylate potassium 1.0
Coenzyme Q10 (CoQ10) 0.03
Dimethylpolysiloxane 5.0
Decamethylcyclopentasiloxane 25.0
Trimethylsiloxysilicate 5.0
Polyoxyethylene / methylpolysiloxane copolymer 2.0
Dipropylene glycol 5.0
Dextrin palmitate coated fine particle zinc oxide (60nm) 15.0
Dipotassium glycyrrhizinate 0.02
Glutathione 1.0
Thiotaurine 0.05
Clara extract 1.0
Paraben appropriate amount phenoxyethanol appropriate amount edetate trisodium appropriate amount 2-methoxyhexyl paramethoxycinnamate 7.5
Dimethyl distearyl ammonium hectorite 0.5
Spherical polyalkyl acrylate powder 5.0
Butylethylpropanediol 0.5
Purified water Residual fragrance

Example 11 Gel (Moisturizing)
3-Methoxysalicylic acid 1.0% by mass
2- (trans-4-aminomethylcyclohexanecarbonyloxy-5-hydroxybenzoic acid 0.1
Dihydrolipoic acid 1.0
Molasses extract 0.1
Coenzyme Q10 (CoQ10) 0.03
Glycerin 2.0
1,3-butylene glycol 5.0
Potassium hydroxide 0.1
Fish collagen 20.0
Edetic acid-3Na 0.05
Carboxyvinyl polymer 0.25
P-Hydroxybenzoate appropriate amount purified water remaining

Example 12 Gel (Whitening)
Potassium 3-propoxysalicylate 0.1% by mass
Dihydrolipoic acid 1.0
Odrichosium 0.1
Dimethylpolysiloxane 5.0
Glycerin 2.0
1,3-butylene glycol 5.0
Polyethylene glycol 1500 3.0
Polyethylene glycol 20000 3.0
Cetyl octanoate 3.0
Citric acid 0.01
Sodium citrate 0.1
Sodium hexametaphosphate 0.1
Dipotassium glycyrrhizinate 0.1
Ascorbic acid glucoside 2.0
Tocopherol acetate 0.1
Ogon Extract 0.1
Yukinoshita extract 0.1
Edetate trisodium 0.1
Xanthan gum 0.3
Acrylic acid / alkyl methacrylate copolymer (Pemulene TR-2) 0.05
Agar powder 1.5
Phenoxyethanol Appropriate amount Dibutylhydroxytoluene Appropriate amount of purified water Residue

Example 13 Pack (Moisturizing)
Trans-4-Aminomethylcyclohexanecarboxylic acid methylamide 10.0% by mass
Dihydrolipoamide 1.0
Ages 0.1
Ethanol 10.0
1,3-butylene glycol 6.0
Polyethylene glycol 4000 2.0
Olive oil 1.0
Macadamia nut oil 1.0
Phytosteryl hydroxystearate 0.05
Lactic acid 0.05
Sodium lactate 0.1
L-ascorbic acid sulfate disodium 0.1
α-Tocopherol 2-L
-Potassium ascorbic acid diester 0.1
Vitamin E acetate 0.1
Fish collagen 0.1
Chondroitin thorium sulfate 0.1
Sodium carboxymethylcellulose 0.2
Polyvinyl alcohol 12.0
Paraoxybenzoic acid ester Appropriate amount Purified water Residual perfume Appropriate amount

Example 14 Pack (Moisturizing)
4-Isoproxysalicylic acid 10.0% by mass
Dihydrolipoamide 1.0
Yukinoshita 0.1
Glycerin 1.0
1,3-butylene glycol 8.0
Xylit 2.0
Polyethylene glycol 1500 2.0
Rosemary oil 0.01
Sage oil 0.1
Citric acid 0.02
Sodium citrate 0.08
Sodium hexametaphosphate 0.01
Hydroxypropyl-β-cyclodextrin 0.1
Aloe extract 0.1
Birch extract 0.1
Lavender oil 0.01
Xanthan gum 0.05
Carboxyvinyl polymer 0.15
P-Hydroxybenzoate appropriate amount purified water remaining

Example 15 Pack (Moisturizing)
Tranexamic acid 1.0% by mass
Dihydrolipoamide 10.0
Ryokucha 0.1
Coenzyme Q10 (CoQ10) 0.3
1,3-butylene glycol 7.0
Sorbit liquid 40.0
Sage oil 0.01
Kaolin 40.0
Citric acid 0.01
Sodium hexametaphosphate 0.05
Calcium chloride 0.01
Magnesium chloride 0.01
Hydroxypropyl-β-cyclodextrin 0.1
Lactic acid 0.01
Trimethylglycine 1.0
Mukuroji extract 0.1
Oat extract 0.1
Lavender oil 0.01
Pyrrolidone carboxylic acid Na 0.01
Quince Seed Extract 0.1
Crystalline cellulose powder 0.7
Sodium carboxymethylcellulose 1.0
Purified water residue

Example 16 Lotion (Moisturizing)
Tranexamic acid 1.0% by mass
4-Butoxysalicylic acid 1.0
Lipoic acid 10.0
Hamelis 0.1
Silica-coated zinc oxide 0.1
Hipotaurine 0.1
Clara extract 0.1
Tounin extract 0.1
Beech bud extract 0.1
Retinol 0.1
Coenzyme Q10 (CoQ10) 0.03
Ethyl alcohol 5.0
Glycerin 1.0
1,3-butylene glycol 5.0
Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.2
Sodium hexametaphosphate 0.03
Trimethylglycine 1.0
Sodium polyaspartate 0.1
α-Tocopherol 2-L
-Potassium ascorbic acid diester 0.1
Thiotaurine 0.1
Green tea extract 0.1
Western mint extract 0.1
Iris Root Extract 1.0
HEDTA3 sodium 0.1
Carboxyvinyl polymer 0.05
Potassium hydroxide 0.02
Phenoxyethanol Appropriate amount Purified water Residual perfume Appropriate amount

Example 17 Lotion (Moisturizing)
Trans-4- (Transaminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid 1.0% by mass
Dihydrolipoic acid 0.01
Enmezo 0.1
Glycerin 2.0
1,3-butylene glycol 4.0
Erythritol 1.0
Polyoxyethylene methyl glucoside 1.0
Polyoxyethylene hydrogenated castor oil 0.5
Citric acid 0.02
Sodium citrate 0.08
Phenoxyethanol appropriate amount N-coconut oil fatty acyl L
-Arginine ethyl DL-pyrrolidone carboxylic acid 0.1
Purified water residue

Example 18 Lotion (Moisturizing)
3-isobutoxysalicylic acid 1.0% by mass
Lipoic acid amide 0.01
Lumpuyan 0.1
Ethanol 5.0
Glycerin 0.5
Dipropylene glycol 2.0
1,3-butylene glycol 6.0
Rosemary oil 0.01
Sage oil 0.01
Citric acid 0.02
Sodium citrate 0.08
Sodium hexametaphosphate 0.03
Hydroxypropyl-β-cyclodextrin 0.1
Mukuroji extract 0.1
Ages Extract 0.1
Lily extract 0.1
Oat extract 0.1
Togenashi extract 0.1
Kiso Extract 0.1
Lavender oil 0.1
Tounin extract 0.1
Sodium alginate 0.001
Purified water residue

Example 19 Lotion (Moisturizing)
Trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester 0.01% by mass
Lipoic acid ethyl ester 1.0
Colladecabaro 0.1
Ethanol 10.0
Glycerin 2.0
Dipropylene glycol 1.0
Isostearic acid 0.1
Poly (oxyethylene / oxypropylene)
・ Methylpolysiloxane copolymer 1.0
Lauryldimethylaminoacetic acid betaine 0.1
Citric acid 0.02
Sodium citrate 0.08
Sodium hexametaphosphate 0.01
Hipotaurine 0.1
Chamomile extract 0.1
Lavender oil 0.001
Phenoxyethanol appropriate amount active hydrogen water 1.0
Purified Water Residual Example 20 Lotion (Whitening)
Potassium 4-methoxysalicylate 0.01% by mass
Lipoic acid ethyl ester 1.0
Jurbeba 0.1
Coenzyme Q10 (CoQ10) 0.03
Ethanol 10.0
Dipropylene glycol 1.0
Polyethylene glycol 1000 1.0
Polyoxyethylene methyl glucoside 1.0
Jojoba oil 0.01
Glyceryl tri-2-ethylhexanoate 0.1
Polyoxyethylene hydrogenated castor oil 0.2
Polyglyceryl diisostearate 0.15
N-stearoyl-L-glutamate sodium 0.1
Citric acid 0.05
Sodium citrate 0.2
Potassium hydroxide 0.4
Dipotassium glycyrrhizinate 0.1
Arginine hydrochloride 0.1
L-ascorbic acid 2-glucoside 2.0
Ogon Extract 0.1
Yukinoshita extract 0.1
Nettle extract 0.1
Tranexamic acid 1.0
Edetate trisodium 0.05
2-Ethylhexyl paramethoxycinnamate 0.01
Dibutylhydroxytoluene Appropriate amount Paraben Appropriate amount Deep sea water 3.0
Purified water Residual fragrance

Example 21 Lotion (Moisturizing)
2- (trans-4-aminomethylcyclohexanecarbonyloxy-5-hydroxybenzoic acid 0.1% by mass
Lipoamide 0.1
Izayoi Rose 0.1
Dimethylpolysiloxane 1.0
Ethanol 3.0
Behenyl alcohol 0.3
Glycerin 5.0
Dipropylene glycol 5.0
Erythritol 1.0
Polyethylene glycol 4000 1.0
Squalane 0.4
Cetyl 2-ethylhexanoate 0.1
N-stearoyl-sodium L-glutamate 0.2
Magnesium chloride 0.1
Arginine chloride 0.1
Hipotaurine 0.1
Edetate trisodium 0.1
Paraben Appropriate amount Purified water Residual perfume Appropriate amount

Example 22 Lotion (Astringent)
Sodium 3-methoxysalicylate 0.1% by mass
Dihydrolipoic acid 0.1
Sakura Leaf 0.1
Ethanol 40.0
Dipropylene glycol 1.0
Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.1
Silicic anhydride 1.0
Salicylic acid 0.1
Sodium citrate 0.2
Zinc paraphenol sulfonate 0.2
Dipotassium glycyrrhizinate 0.1
Pyridoxine hydrochloride 0.1
L-Menthol 0.05
HEDTA3 sodium 0.05
Cellulose powder 1.0
Bentonite 0.8
Purified water residue

Example 23 Lotion (Moisturizing)
Trans-4-aminomethylcyclohexanecarboxylic acid methylamide 0.01% by mass
Lipoic acid 0.01
Coco Huitt 0.1
Vitamin A acetate 0.1
Vitamin A palmitate 0.1
Asenyak 0.1
Hinogi 0.1
Ibukijakou 0.1
Psycho extract 0.1
Turmeric 0.1
Lysoletin 0.1
Glycerin 1.0
Dipropylene glycol 12.0
Ethanol 8.0
POE methyl glucoside 3.0
POE (24) POP (13)
Decyl tetradecyl ether 0.5% by mass
Citric acid 0.02
Sodium citrate 0.08
Hydroxypropyl-β-cyclodextrin 0.5
Thiotaurine 0.1
Adenosine triphosphate-2 sodium 0.1
Sodium hyaluronate 0.01
EDTA3 sodium 0.01
Hydroxyethyl cellulose 0.1
Paraben Appropriate amount Purified water Residual perfume Appropriate amount

Example 24 Latex (Moisturizing)
Tranexamic acid 1.0% by mass
4-Ethoxysalicylic acid 0.01
Lipoic acid 0.01
Paloazul 0.1
Dimethylpolysiloxane 3.0
Decamethylcyclopentasiloxane 4.0
Ethanol 5.0
Glycerin 6.0
1,3-butylene glycol 5.0
Polyoxyethylene methyl glucoside 3.0
Sunflower oil 1.0
Squalane 2.0
Potassium hydroxide 0.1
Sodium hexametaphosphate 0.05
Hydroxypropyl-β-cyclodextrin 0.1
Dipotassium glycyrrhizinate 0.05
Loquat leaf extract 0.1
Sodium L-glutamate 0.05
Fennel extract 0.1
Yeast extract 0.1
Lavender oil 0.1
Giant extract 0.1
Dimorpholinopyridazinone 0.1
Xanthan gum 0.1
Carboxyvinyl polymer 0.1
Acrylic acid / alkyl methacrylate copolymer (Pemulene TR-1) 0.1
Bengala Appropriate amount Yellow iron oxide Appropriate amount Paraben Appropriate amount Purified water Residual

Example 25 Latex (Moisturizing)
Trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester 0.01% by mass
Lipoic acid 0.1
Marjoram 0.1
Dimethylpolysiloxane 2.0
Behenyl alcohol 1.0
Batyl alcohol 0.5
Glycerin 5.0
1,3-butylene glycol 7.0
Erythritol 2.0
Hardened oil 3.0
Squalane 6.0
Tetra-2-ethylhexanoic acid pentaerythrit 2.0
Polyoxyethylene glyceryl isostearate 1.0
Polyoxyethylene glycerol monostearate 1.0
Potassium hydroxide appropriate amount Sodium hexametaphosphate 0.05
Phenoxyethanol appropriate amount carboxyvinyl polymer 0.1
Purified water residue

Example 26 Latex (Moisturizing)
Potassium 3-propoxysalicylate 0.01% by mass
Lipoic acid 0.1
α-Glucosyl hesperidin 0.1
Liquid paraffin 7.0
Vaseline 3.0
Decamethylcyclopentasiloxane 2.0
Behenyl alcohol 1.0
Glycerin 5.0
Dipropylene glycol 7.0
Polyethylene glycol 1500 2.0
Jojoba oil 1.0
Isostearic acid 0.5
Stearic acid 0.5
Behenic acid 0.5
Tetra-2-ethylhexanoic acid pentaerythritol 3.0
Cetyl 2-ethylhexanoate 3.0
Glycerol monostearate 1.0
Polyoxyethylene glycerol monostearate 1.0
Potassium hydroxide 0.1
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.05
L-Arginine 0.1
Royal Jelly Extract 0.1
Yeast extract 0.1
Tocopherol acetate 0.1
Acetylated sodium hyaluronate 0.1
Edetate trisodium 0.05
4-t-butyl-4'-methoxydibenzoylmethane 0.1
2-Ethylhexyl paramethoxycinnamate 0.1
Carboxyvinyl polymer 0.15
Paraben Appropriate amount Purified water Residual perfume Appropriate amount

Example 27 Latex (Anti-aging)
Tranexamic acid 0.1% by mass
Lipoic acid ethyl ester 0.01
Serine 0.1
Decamethylcyclopentasiloxane 15.0
Trimethylsiloxysilicate 5.0
Polyoxyethylene / methylpolysiloxane copolymer 5.0
Glycerin 5.0
1,3-butylene glycol 5.0
Maltitol solution 2.0
Macadamia nut oil 2.0
Squalane 2.0
Cholesteryl hydroxystearate 0.5
Cetyl 2-ethylhexanoate 2.0
Distearyldimethylammonium chloride 0.2
L-ascorbic acid sulfate disodium 0.1
α-Tocopherol 2-L-ascorbic acid phosphate diester potassium 0.1
Tocopherol acetate 0.05
Fish collagen 0.4
Sodium chondroitin sulfate 0.01
Sodium hyaluronate 0.1
Edetate trisodium 0.05
Diparamethoxycinnamic acid mono-2-ethylhexanoate glyceryl 0.05
Aluminum magnesium silicate 0.3
Paraben Appropriate amount of purified water Residual

Example 28 Latex (Anti-aging)
4-Isoproxysalicylic acid 0.1% by mass
Lipoic acid 0.01
Trimethylglycine 0.1
Vaseline 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.5
Glycerin 7.0
1,3-butylene glycol 7.0
1,2-pentanediol 1.0
Xylit 3.0
Polyethylene glycol 20000 2.0
Hardened oil 2.0
Jojoba oil 2.0
Squalane 5.0
Isostearic acid 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 2.0
Polyoxyethylene hydrogenated castor oil 0.5
Lauryldimethylaminoacetic acid betaine 0.4
Potassium hydroxide appropriate amount Sodium pyrosulfite 0.01
Sodium hexametaphosphate 0.05
Dipotassium glycyrrhizinate 0.05
Trimethylglycine 3.0
Arbutin 3.0
Yeast extract 0.1
Tocopherol acetate 0.1
Thiotaurine 0.1
Clara extract 0.1
Bengala appropriate amount quince seed extract 0.1
Carboxyvinyl polymer 0.2
Phenoxyethanol Suitable amount Purified water Residual

Example 29 Latex (Anti-aging)
Trans-4- (Transaminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid 1.0% by mass
Lipoic acid 0.001
Akebi extract 0.1
Vaseline 5.0
Dimethylpolysiloxane 2.0
Behenyl alcohol 0.6
Batyl alcohol 0.5
Dipropylene glycol 2.0
1,3-butylene glycol 4.0
Xylit 1.0
Polyethylene glycol 1500 1.0
Squalane 5.0
Glyceryl tri-2-ethylhexanoate 2.0
Polyoxyethylene hydrogenated castor oil 0.5
Dipotassium glycyrrhizinate 0.1
Yeast extract 0.1
Peonies extract 0.1
HEDTA trisodium 0.05
Xanthan gum 0.1
Carboxyvinyl polymer 0.15
Purified water

Example 30 Latex (Protector)
4-Butoxysalicylic acid 1.0 mass%
Dihydrolipoic acid 0.001
Arginine (hydrochloride) 0.1
Vaseline 1.0
Dimethylpolysiloxane 3.0
Methylphenylpolysiloxane 3.0
Stearyl alcohol 0.5
Glycerin 7.0
Dipropylene glycol 3.0
1,3-butylene glycol 7.0
Xylitol 3.0
Squalane 1.0
Isostearic acid 0.5
Stearic acid 0.5
Polyoxyethylene glycerol monostearate 1.0
Glycerol monostearate 2.0
Potassium hydroxide 0.05
L-ascorbyl magnesium phosphate 0.1
Tocopherol acetate 0.1
Acetylated sodium hyaluronate 0.1
HEDTA trisodium 0.05
4-t-butyl-4′-methoxydibenzoylmethane 2.0
2-Ethylhexyl paramethoxycinnamate 5.0
Carboxyvinyl polymer 0.1
Phenoxyethanol Appropriate amount Purified water Residual perfume Appropriate amount

Example 31 Latex (Protector)
Trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester 0.1% by mass
Dihydrolipoic acid 0.001
Xylitol 0.1
Cetanol 1.0
Glycerin 5.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 2.0
Tetra (2-ethylhexanoic acid / paramethoxycinnamic acid)
Pentaeri slit 3.0
Di-2-ethylhexyl succinate 3.0
Potassium hydroxide 0.1
Edetate trisodium 0.1
Methylbis (trimethylsiloxy) silylisopentyl trimethoxycinnamate 2.0
4-t-butyl-4′-methoxydibenzoylmethane 2.0
2-Ethylhexyl paramethoxycinnamate 2.0
Diparamethoxycinnamate mono-2-ethylhexanoate glyceryl 2.0
Carboxyvinyl polymer 0.15
Acrylic acid / alkyl methacrylate copolymer (Pemulene TR-1) 0.1
Paraben Appropriate amount Phenoxyethanol Appropriate amount Purified water Residual fragrance Appropriate amount

Example 32 Dry Water Aerosil RY200S 5.0% by mass
Silicone powder E506-W 3.0
Tranexamic acid 1.0
Lipoic acid 0.1
1,3-butylene glycol 10.0
Citric acid 0.03
Sodium citrate 0.07
Potassium hydroxide 0.2
Paraben Appropriate amount of purified water Residual

Example 33 Dry Water Aerosil RY200S 4.0% by mass
Sildex L-51 3.0
4-Methoxysalicylate Na 1.0
Lipoic acid 0.1
Pantotenyl ethyl ether 0.1
1,3-butylene glycol 10.0
Dynamite Glycerin 3.0
Citric acid 0.01
Sodium citrate 0.09
Paraben Appropriate amount of purified water Residual

Example 34 Emulsified solid 3-isobutoxysalicylic acid 0.1% by mass
Lipoic acid ethyl ester 0.001
Aminomethylcyclohexanecarbonamide 0.1
Microcrystalline wax 1.0
Dimethylpolysiloxane 15.0
Decamethylcyclopentasiloxane 2.0
1,3-butylene glycol 6.0
Candelilla Row 3.0
Isostearic acid 1.0
Ethylene glycol fatty acid ester 0.1
Lanolin fatty acid octyldodecyl 0.5
2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine 4.0
Titanium oxide 7.5
Barium sulfate 5.0
Titanium oxide 7.0
Talc 3.0
Silicic anhydride 4.0
Cross-linked silicone powder (Trefil E-506) 0.1
Sodium metaphosphate 0.1
Hydroxypropyl-β-cyclodextrin 0.1
DL-α-tocopherol acetate 0.1
Hamamelis extract 0.1
Peonies extract 0.1
Sodium chondroitin sulfate 0.1
Sodium hyaluronate 0.1
Paraoxybenzoic acid appropriate amount Bengala appropriate amount yellow iron oxide appropriate amount black iron oxide appropriate amount xanthan gum 0.2
Sodium carboxymethylcellulose 0.2
Merirot Extract 2.0
Purified water residue

Example 35 Cream Foundation 2- (Trans-4-aminomethylcyclohexanecarbonyloxy-5-hydroxybenzoic acid 1.0% by mass
Lipoic acid 1.0
Ichiyakuso Extract 0.1
Dimethylpolysiloxane 3.0
Decamethylcyclopentasiloxane 10.0
Polyoxyethylene / methylpolysiloxane copolymer 3.0
Dodecamethylcyclohexasiloxane 5.0
Glycerin 4.0
1 3-butylene glycol 5.0
Palmitic acid 0.5
Distearyldimethylammonium chloride 0.2
Metal soap treated talc 2.0
Cross-linked silicone powder (Trefil E-506) 0.1
Bengala-coated mica titanium 0.5
N-lauroyl-L-lysine 2.0
Sodium L-glutamate 2.0
Tocopherol acetate 0.1
δ-tocopherol 0.1
P-Hydroxybenzoate appropriate amount Phenoxyethanol 0.2
Spherical nylon powder 1.0
Spherical polyalkyl acrylate powder 3.0
Merirot Extract 2.0
Purified water Residual dextrin fatty acid-treated talc 3.0
Dextrin fatty acid treated titanium dioxide 15.0
Dextrin fatty acid-treated yellow iron oxide 3.0
Dextrin fatty acid-treated black iron oxide 0.5

Claims (4)

  Whitening characterized by comprising one or more selected from tranexamic acid and derivatives thereof, alkoxysalicylic acid and salts thereof, and one or more selected from α-lipoic acid and derivatives and salts thereof. Agent.   A skin external preparation for whitening comprising the whitening agent according to claim 1.   0.001-20.0% by mass of one or more selected from tranexamic acid and derivatives thereof, alkoxysalicylic acid and salts thereof, and one or two selected from α-lipoic acid and derivatives and salts thereof The skin external preparation for whitening according to claim 2, containing 0.001 to 20.0 mass% of the above. A whitening method comprising whitening the skin using the whitening agent according to claim 1.