JP2006182713A - Bleaching agent and food, pharmaceutical composition and cosmetic containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compound useful as a bleaching agent and to provide a food, a pharmaceutical composition and a cosmetic containing the compound. <P>SOLUTION: It is found out that 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxyphenyl)-naphthalene [a compound represented by formula (I)] which is the compound extracted and isolated from Acanthopanax sessiliflorus has strong suppressive actions on melanin formation and inhibitory actions on the tyrosinase activity. The compound is used as the bleaching agent to achieve the accomplishment. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention provides a whitening agent, a melanin production inhibitor, a tyrosinase activity inhibitor, and foods, pharmaceutical compositions, and cosmetics containing them, which are effective in the prevention and treatment of cosmetic disorders such as spots and buckwheat. It is.

The amount of ultraviolet rays that reach the epidermis due to air pollution and destruction of the ozone layer tends to increase year by year, and accordingly, skin problems such as skin spots, buckwheat, and dark black due to ultraviolet rays are increasing.
Conventionally, many whitening cosmetics, foods and medicines for sunburn, spots and the like have been developed. It is known that pigmentation is derived from ultraviolet rays and inflammation, and the pigment is melanin. As a mechanism to suppress the production of such melanin pigment, it suppresses the activity of tyrosinase, an enzyme that synthesizes melanin, reduces melanin to become colorless, prevents inflammation that induces melanin synthesis, There is a suppression of the production of active oxygen, and such a mechanism has been studied.

In cosmetics, for preventing or suppressing such pigmentation, reducing agents such as vitamin C and vitamin E, tyrosinase activity inhibitors such as kojic acid and arbutin, antioxidant components such as proanthocyanidins, tranexamic acid, etc. It is generally known that applying an anti-inflammatory component is effective.
Among them, for example, skin cosmetics containing L-ascorbic acid and its derivative L-ascorbic acid glucose glycoside (see Patent Document 1), L-ascorbic acid glucose glycoside and amino acid or A skin external preparation (see Patent Document 2) or the like in which the derivatives are combined and blended has been proposed.

  Examples of the medicament include SH group preparations such as cysteine and glutathione, those containing colloidal sulfur and hydroquinone, and oral whitening medicine containing tranexamic acid and ascorbic acid (see Patent Document 3).

  Many foods that contain water-soluble vitamins such as kojic acid, grape seed extract and ascorbic acid, or salts thereof have been developed. For example, whitening foods containing kojic acid and fatty acid esters thereof (patents) Document 4) is known.

  However, these whitening agents are those in which the whitening effect is not sufficiently observed, or if an ingredient showing the whitening effect is mixed in a concentration at which the whitening effect is recognized, problems such as safety and stability may occur. , Often recognized.

The investigator has been eagerly researching on whitening agents, and extracted from Acanthopanax sessiliflorus, 3-carboxy-6,7-dihydroxy-1- (3 ', 4'-dihydroxyphenyl) -naphthalene A patent application was filed for an antioxidant containing (Compound I) as an active ingredient (see Patent Document 5). As a result of further research and development, the present invention has newly found that Compound I has a melanin production inhibitory action and a tyrosinase activity inhibitory action, that is, a whitening action.
JP-A-4-18212 JP-A-4-182413 JP-A-4-243825 JP 60-137253 A Japanese Patent Application No. 2003-409945

  An object of the present invention is to provide a compound useful as a whitening agent, a melanin production inhibitor, or a tyrosinase activity inhibitor that is extremely effective in blackening the skin due to sunburn, etc. It aims at providing the foodstuff, pharmaceutical composition, and cosmetics containing this.

As a result of diligent research in order to solve the above-mentioned problems, the present inventors are compounds that are extracted and isolated from Manshukogi.
3-carboxy-6,7-dihydroxy-1- (3 ', 4'-dihydroxyphenyl) -naphthalene (Compound I) was found to have strong melanin production inhibitory activity and tyrosinase activity inhibitory activity, and Compound I as a whitening agent It was found that it can be used, and the present invention was completed.
The main configuration of the present invention is as follows.
(1) represented by the following formula (I)
A whitening agent containing 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) and / or a physiologically acceptable salt thereof.
(2) 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) represented by the following formula (I) and / or a physiologically acceptable salt thereof A whitening agent comprising a dried body or extract of a plant containing.
(3) The whitening agent according to (2) above, wherein the plant is Acanthopanax sessiliflorus.
(4) A food containing the whitening agent according to any one of (1) to (3).
(5) A pharmaceutical composition comprising the whitening agent according to any one of (1) to (3) as an active ingredient.
(6) A cosmetic containing the whitening agent according to any one of (1) to (3).

  3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (hereinafter referred to as “Compound I”) of the present invention has a strong melanin production inhibitory action and tyrosinase activity inhibitory action. It is excellent in that point. In addition, since Compound I is obtained from Acanthopanax sessiliflorus, which is a natural product and used as a crude drug, it is preferable in that it has little influence on the biological system. Therefore, the whitening agent containing Compound I of the present invention and / or a physiologically acceptable salt thereof (hereinafter sometimes simply referred to as “Compound I etc.”) is applicable to foods, pharmaceutical compositions and cosmetics. In particular, it is effective for the prevention and treatment of skin blackening, spots, freckles and the like.

The compound I used in the present invention is obtained from the leaves of Acanthopanax sessiliflorus belonging to the genus Argiaceae, but as long as it contains the same compound, the production area is particularly limited. In addition, the type of plant is not particularly limited as long as it is a plant containing the compound of the present invention.
Acanthopanax sessiliflorus in the present invention is also called Goka, and its root bark is used as a raw material for traditional Chinese medicines such as nutrition tonic and fatigue recovery.

  In the present invention, Acanthopanax sessiliflorus can be used at any site containing Compound I of the present invention. It includes all parts such as leaves, stems, buds, flowers, woody parts, above-ground parts of bark parts (bark) and underground parts such as roots and tubers, seeds, fruits, and resins.

  Further, a dried product obtained by drying the plant itself, a pulverized product thereof, a juice obtained by squeezing and extracting the product itself, a crude extract using water or a solvent such as ethyl alcohol, methyl alcohol, diethyl ether, acetone, Compound I obtained by stepwise purification of the extract by various chromatographies such as partitioning and column chromatography can be used. The obtained extract fraction may be concentrated by an appropriate method, or spray-dried or freeze-dried. These may be used alone or in combination of two or more.

For example, an extract obtained by adding 3 L of 99.5% ethanol to 1 kg of dried leaves of Acanthopanax sessiliflorus and soaking overnight at room temperature is used as it is, a melanin production inhibitor, a tyrosinase activity inhibitor, or You may use as a whitening agent and the foodstuff, pharmaceutical composition, or cosmetics containing them, and you may use the thing refine | purified combining various chromatography.
The extract containing Compound I or the like is preferably an ethyl acetate-soluble fraction obtained by liquid-liquid partitioning of hot water extract of Acanthopanax sessiliflorus leaves using ethyl acetate / water. .

Further, as described above, Compound I and the like may be extracted and purified from the plant body of Acanthopanax sessiliflorus, but can also be obtained by chemical synthesis. For example, the present compound can be synthesized by a known method as described in the following references.
Reference: Phytochemistry, Vol.28, No.3, pp867-869, 1989.

It has not been known so far that the compound I or the like according to the present invention has a melanin production inhibitory action or a tyrosinase activity inhibitory action, and is a new finding obtained by the present invention.
Moreover, since compound I etc. have a strong melanin production inhibitory action or a tyrosinase activity inhibitory action, it can be used as a whitening agent. Further, by using foods, pharmaceutical compositions or cosmetics containing these, it is possible to prevent and treat skin blackening, spots, freckles and the like.

  As the melanin production inhibitor, tyrosinase activity inhibitor or whitening agent of the present invention, a physiologically acceptable salt of this compound can be used in addition to the compound I obtained as described above. In this case, one type of Compound I and a salt thereof may be used alone, or two or more types may be mixed and used.

  Such salts are not particularly limited as long as they are physiologically acceptable. For example, salts with alkali metals such as sodium and potassium, and salts with alkaline earth metals such as calcium and magnesium. And salts with amines such as ammonia, triethylamine and triethanolamine, and salts with basic amino acids such as arginine and lysine.

  Further, when a modified product of Compound I is used as a pharmaceutical product, the modified product (prodrug) is also within the scope of the pharmaceutical composition of the present invention. Such modified products include salts and esters of Compound I.

  The melanin production inhibitor, tyrosinase activity inhibitor, or whitening agent of the present invention is a melanin production inhibitor, tyrosinase activity inhibitor, or whitening agent containing Compound I and / or a physiologically acceptable salt thereof. However, a compound having a structure such as compound II represented by the following formula can be used instead of compound I. That is, the hydrogen atom of the 3-position carboxyl group (—COOH) of the naphthalene skeleton of Compound I is replaced with another group. For example, R is a residue obtained by removing a hydroxyl group from alcohols or phenols. In particular, a hydrocarbon group having 10 or less carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, and a butyl group is preferable, and may be a phenyl group.

[Whitening agent, melanin production inhibitor, tyrosinase activity inhibitor, pharmaceutical composition]
Whitening in the present invention means that the original skin color becomes white, that the skin that has been blackened due to sunburn, etc. becomes white, that blackening is prevented, that spots and freckles are thin and inconspicuous, And the generation of buckwheat is suppressed. Specifically, in the present invention, the whitening effect was confirmed by the presence or absence of a tyrosinase activity inhibiting action and / or a melanin production inhibiting action.
The suppression of melanin production in the present invention is to suppress the production of melanin pigment. In the present invention, the compound (I) of the present invention is added to the melanoma cell which is a melanin-producing cell, and the production rate of melanin pigment is expressed as absorbance. The effect was confirmed by calculating | requiring by measurement and calculating | requiring a melanin production | generation suppression rate in relation to the thing which does not add compound (I).
The inhibition of tyrosinase activity in the present invention refers to inhibiting the activity of tyrosinase. In the present invention, compound (I) is added to a solution containing tyrosinase and L-DOPA (intermediate substance of melanin biosynthesis), and compound (I The inhibitory effect of tyrosinase activity was confirmed in relation to those without addition of I).

  The whitening agent, melanin production inhibitor, tyrosinase activity inhibitor or pharmaceutical composition containing these of the present invention can be employed either orally or parenterally. Examples of parenteral administration include transdermal administration, rectal administration, and injection. A conventional pharmaceutical preparation prepared by mixing a solid or liquid non-toxic pharmaceutical carrier suitable for each oral or parenteral administration method and the melanin production inhibitor, tyrosinase activity inhibitor or whitening agent of the present invention. Can be administered. Examples of such preparations include solid preparations such as tablets, granules, powders and capsules, solutions such as solutions, suspensions and emulsions, freeze-dried preparations, and the like. It can be prepared by conventional means.

  Examples of the non-toxic pharmaceutical carrier include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, Examples include albumin, water, and physiological saline. Further, if necessary, conventional additives such as a stabilizer, a wetting agent, an emulsifier, a binder, and an isotonic agent can be appropriately added.

[Food]
As a food, it can be blended as it is, with various nutritional components added, or together with optional components usually used in foods. For example, it is included in confectionery, drinks, bread, etc., and is eaten as a health food or food material useful for the prevention and treatment of skin blackening, spots, buckwheat, and the like. For example, after adding an appropriate auxiliary agent to Compound I etc., it can be used for edible by using conventional means and forming it into an edible form, for example, granule, granule, tablet, capsule, paste, etc. Well, various foods, for example, processed foods such as ham and sausage, processed fish foods such as kamaboko and chikuwa, bread, confectionery, butter, powdered milk, fermented dairy products, water, fruit juice, You may add and use for drinks, such as milk, tea, and a soft drink.

  In the present invention, an effective intake amount of Compound I or the like is appropriately selected and determined according to the age, weight, symptoms, administration route, administration schedule, formulation form, strength of the inhibitory activity of the material, etc. For example, in the case of oral administration, it is generally about 0.001 to 1000 mg / kg body weight per day, and may be administered in several divided doses.

  Compound I of the present invention has low toxicity. For example, even when Compound I is orally administered to rats for a long period of 1000 mg / kg every day for 100 days, no deaths are observed, and no change in body weight is observed. It was.

[Cosmetics]
The cosmetic containing the whitening agent, the melanin production inhibitor, and the tyrosinase activity inhibitor of the present invention is used for preventing skin blackening, spots, freckles, and the like. As a cosmetic to which the present invention is applied, the dosage form is not particularly limited, and for example, it can be used for the following uses. Makeup cosmetics such as lotion, milky lotion, cream, beauty liquid, pack cosmetics, makeup cosmetics such as foundation, under makeup, white powder, hair makeup such as hand cream, hair tonic, hair liquid, shampoo, rinse Fees. These cosmetics can be produced in the same manner as ordinary cosmetics except that the above compound I is blended.

The amount of compound I or the like of the present invention in the cosmetic is not particularly limited, but is preferably in the range of 0.001 to 10% by weight relative to the total amount of the cosmetic, and more preferably in the range of 0.01 to 1% by weight. More preferably, it is blended. If the compounding amount of compound I is less than 0.001% by weight, the effect of preventing skin blackening, spots, freckles, etc. may not be obtained sufficiently, and if it exceeds 10% by weight, the effect will reach its peak. It is often not economical.
In addition, when using the fraction of an extract, it can use similarly by converting into a compound density | concentration so that an effect comparable as the said density | concentration may be acquired.

  In addition to the whitening agent containing Compound I and the like, a melanin production inhibitor, and a tyrosinase activity inhibitor, the cosmetics of the present invention can be blended with various components commonly used in cosmetics. For example, hydrocarbons such as petroleum jelly and liquid paraffin, esters such as jojoba oil and carnauba wax, triglycerides such as olive oil and beef tallow, higher alcohols such as stearyl alcohol and behenyl alcohol, fatty acids such as stearic acid and behenic acid, Nonionic surfactants such as glyceryl monostearate, polyoxyethylene stearic acid, polyoxyethylene hydrogenated castor oil, polyoxyethylene stearyl ether, anionic surfactants such as soap and sulfate ester, cationic surfactants such as stearylamine, Amphoteric surfactants such as alkylbetaines, polyhydric alcohols such as glycerin and propylene glycol, various powder components, moisturizers, thickeners, colorants, fragrances, pH adjusters, chelating agents, preservatives, or UV protection agents , Anti-inflammatory agents, whitening agents, etc. That.

  Furthermore, the cosmetic of the present invention can be used in combination with other substances having the same action as those other than the whitening agent containing Compound I and the like, a melanin production inhibitor, and a tyrosinase activity inhibitor.

Next, although an example is given and explained concretely, it is not limited to this.
Production example
Extraction from leaves of Acanthopanax sessiliflorus <br/> The leaves of Acanthopanax sessiliflorus were collected from Changbai Mountain, Jilin Province, China from mid-August to early September. 80 L of water was added to 10 kg of the dried leaf and extracted at 90 ° C. for 1 hour to obtain an extract. The extract was filtered using a 60 mesh filter, concentrated at 60 ° C. until the Brix (soluble solids concentration) was about 10, and filtered through a 250 mesh filter. This was sterilized at 130 ° C for 30 seconds, spray-dried (inlet temperature: 140 ° C, outlet temperature: 80 ° C), and sieved with a 30 mesh filter. (Yield: 22%) was obtained.

Isolation of 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) As shown in FIG. , Abbreviated as cc).
That is, the hot water extract (1630.63 g) of the leaf of Manxukogi obtained in the above production example was subjected to liquid-liquid partition using ethyl acetate and water to obtain an ethyl acetate soluble fraction (21.27 g). It was. The obtained ethyl acetate soluble fraction was applied to Sephadex LH-20 (Pharmacia Fine Chemical Co.) cc, and eluted with methanol to obtain four fractions L-1 to L-4 (L-1 : 9.69 g, L-2: 5.69 g, L-3: 4.63 g, L-4: 0.25 g). Next, the L-4 fraction (0.25 g) was subjected to ODS (Chromatorex ODS: manufactured by Fuji Silysia Chemical Ltd.) cc, and a 50% (v / v) methanol solution containing 0.01% trifluoroacetic acid (TFA) was used. 9 fractions of O-1 to O-9 (O-1: 13.1 mg, O-2: 7.6 mg, O-3: 5.0 mg, O-4: 117.2 mg, O-5: 34.8 mg, O-6: 4.1 mg, O-7: 34.8 mg, O-8: 62.0 mg, O-9: 10.6 mg). Furthermore, O-4 and O-5 were combined (152.0 mg), Silica gel ( Kieselgel 60 F 254, Merck) was subjected to cc, chloroform: methanol: water (80: 20: 2 v / v / v) mixture The compound of the present invention, 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) (68.1 mg, yield: 0.0042% )

Spectral data The spectral data of the obtained compound I of the present invention was measured, and the results shown below were obtained.
Colorless microcrystalline powder
mp: 325-327 ° C (decomposition point)
Molecular weight: 312.2
EI-MS (70eV);
m / z (%): 312 (100, M ⁺ ), 249 (11), 221 (20), 165 (7), 163 (8)
HR-FAB-MS (m / z): 313.0690 ([M + H] ⁺ : C ₁₇ H ₁₃ O ₆ requires 313.0712)
Molecular composition: C 65.39, H 3.87, O 30.74
IR spectrum: see Figure 2
¹ H NMR (500 MHz) and ¹³ C NMR (125 MHz): see Table 1

Pharmacological test
Measurement of melanin production inhibitory activity Melanin production inhibitory activity was evaluated by the following test using Compound I isolated by the method shown in the Production Example.
Cultured B16 melanoma cells derived from mice as cells that produce melanin are cultured in Eagle's MEM medium supplemented with 10% fetal bovine serum, and the cells are transferred to each well of a 6-well plate at a concentration of 2 × 10 ⁴ cells / well. Seeding and culturing in a CO ₂ incubator for 5 days. Thereafter, the sample was replaced with a fresh medium to which the compound (I) of the present invention was added at concentrations of 0.01, 0.03, 0.1 and 0.3 mg / ml, and further cultured under the same conditions for 3 days. After washing the cultured cells, culture plates the cells are detached with a scraper from solubilized by sodium dodecyl sulfate 475 nm is indicative of the amount of melanin, by measuring the absorbance at 260 nm which is an index of cell mass, S ₄₇₅ , _S260 . Absorbance at 475 nm and 260 nm of the cells cultured in a medium to which compound (I) was not added was measured to _obtain C ₄₇₅ and C ₂₆₀ . The melanin production inhibition rate was calculated by the following formula 1. Kojic acid was used as a positive control. A graph showing the relationship between the amount of compound (I) added and the melanin inhibition rate is shown in FIG. In addition, Table 1 shows 50% inhibition concentration values (IC ₅₀ values) obtained from these results.

Measurement of tyrosinase activity inhibitory activity Tyrosinase inhibitory activity was evaluated by the following test using Compound I isolated by the method shown in the Production Example.
As a sample, 0.05 ml of a 600 units / ml Tyrosinase solution was added to 0.95 ml of a solution obtained by adding the compound (I) of the present invention to a final concentration of 0.16, 0.31, 0.63, 1.25, 2.5, 5 mM, Incubated for 10 minutes at ° C. Thereafter, 0.5 ml of a 6 mM L-DOPA solution previously warmed to 30 ° C. was added, and incubated at 30 ° C. with shaking for 40 minutes. A 100 mM succinate buffer (pH 5.5) was used for dilution of the sample solution, Tyrosinase, and L-DOPA. After shaking, absorbance was measured at a wavelength of 475 nm, which is an index of the amount of melanin, and this value was _{designated as S475} . Control (C) without compound (I), absorbance at C ₄₇₅ , sample without L-DOPA (SB), absorbance at SB ₄₇₅ , sample without L-DOPA The control blank (CB), this absorbance was CB _475, and the tyrosinase inhibition rate was calculated according to Equation 2. Kojic acid was used as a positive control. From this result, a graph showing the relationship between the amount of compound (I) added and the inhibition rate of tyrosinase activity is shown in FIG. 4, and it can be seen that compound I exhibits a whitening effect. Further, the IC ₅₀ value was smaller than that of kojic acid used as a positive control, indicating that Compound I has a high melanin production inhibitory action.

As shown in FIG. 3, it can be seen that addition of Compound I inhibits tyrosinase activity, and Compound I exhibits a whitening effect.

A prescription example is shown below.
Formulation Example 1
[Manufacture of tablets]
Using 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) obtained in Production Example, tablets having the following composition were produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 24
Lactose 63
Cornstarch 12
Guar gum 1

Formulation example 2
[Manufacture of juice]
Using the compound I obtained in Production Example, a juice having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.2
Frozen concentrated Wenzhou orange juice 5.0
Fructose glucose liquid sugar 11.0
Citric acid 0.2
L-ascorbic acid 0.02
Fragrance 0.2
Dye 0.1
Wed 83.28

Formulation Example 3
[Manufacture of cosmetics (hand cream)]
Using the compound I obtained in the production example, a hand cream having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.5
Cetanol 8.0
Stearyl alcohol 2.0
Polyoxyethylene lauryl ether 1.5
Propylene glycol 6.0
Sorbitol 1.0
Paraben 0.4
Vitamin E 0.5
Fragrance 0.1
Purified water 66.0

Formulation Example 4
[Manufacture of cosmetics (skin lotion)]
Using the compound I obtained in the production example, a lotion having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.1
1,3-Butylene glycol 8.5
Glycerin 1.5
L-serine 0.1
Mixed isomerized sugar 1.0
Parsley extract 0.1
Rosemary extract 0.3
Purified water 88.4

Formulation Example 5
[Manufacture of cosmetics (milky lotion)]
Using Compound I obtained in Production Example, an emulsion having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.2
1,3-Butylene glycol 8.0
Carboxyvinyl polymer 0.12
Glycerin 3.0
Mixed isomerized sugar 0.5
L-threonine 0.1
Jojoba oil 1.5
Squalane 1.5
Polyoxyethylene hydrogenated castor oil 1.0
Parsley extract 0.1
Potassium hydroxide 0.04
Purified water 83.94

Formulation Example 6
[Manufacture of cosmetics (beauty solution)]
Using Compound I obtained in Production Example, a beauty solution having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.2
1,3-Butylene glycol 8.0
Trimethylglycine 2.0
Glycerin 5.0
Mixed isomerized sugar 3.0
Carboxyvinyl polymer 0.15
Potassium hydroxide 0.05
Sodium hyaluronate (1% aqueous solution) 0.5
Purified water 81.1

Formulation Example 7
[Manufacture of cosmetics (pack cosmetics)]
Using the compound I obtained in Production Example, a pack cosmetic having the following composition was produced according to a conventional method.

(Composition) (Composition: Weight%)
Compound I 0.2
Dextran 11.5
Carboxyvinyl polymer 0.3
Diglycerin 17.0
Trimethylglycine 2.0
L-serine 0.1
Mixed isomerized sugar 0.5
Maltitol 4.0
1,3-Butylene glycol 10.0
Polyoxyethylene hydrogenated castor oil 0.5
Sodium carboxymethylcellulose 1.4
Potassium hydroxide 0.1
Capsules containing salt 0.1
Purified water 52.3

  The whitening agent, melanin production inhibitor, and tyrosinase activity inhibitor of the present invention can be applied to pharmaceutical compositions, foods, and cosmetics, and are particularly effective for the prevention and treatment of skin blackening, spots, freckles, etc. It is.

It is a figure which shows the isolation / purification method of 3-carboxy-6,7-dihydroxy-1- (3 ', 4'-dihydroxyphenyl) -naphthalene (compound I). It is a figure which shows IR spectrum of compound (I). It is a graph showing the relationship between the addition amount of compound (I), and a melanin suppression rate. It is a graph showing the relationship between the addition amount of compound (I) and the tyrosinase activity inhibition rate.

Claims (6)

Represented by the following formula (I)
A whitening agent containing 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) and / or a physiologically acceptable salt thereof.
Contains 3-carboxy-6,7-dihydroxy-1- (3 ′, 4′-dihydroxyphenyl) -naphthalene (Compound I) and / or a physiologically acceptable salt thereof represented by the following formula (I) Whitening agent containing dried plant or extract.
  The whitening agent according to claim 2, wherein the plant is Acanthopanax sessiliflorus.   The foodstuff containing the whitening agent in any one of Claims 1-3.   The pharmaceutical composition which uses the whitening agent in any one of Claims 1-3 as an active ingredient. Cosmetics containing the whitening agent in any one of Claims 1-3.