JP2557241B2 - Anti-pigmenting agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel antipigmenting agent. More specifically, it relates to a highly safe anti-pigmenting agent containing sialic acid or a sialic acid derivative as an active ingredient.

[Conventional technology]

Examples of the pigmentation diseases include erythrocytic spots, liver spots, black spots, senile pigment spots, petaloid pigmentation, actinic keratosis, pigmented nevus, nevus of Ota, and Bellrock dermatitis. There are many unclear points about the mechanism of the occurrence of these pigmentation, and in general, genetic factors, hormonal abnormalities, stimulation of sunlight ultraviolet rays,
It is considered that abnormal deposition occurs in the skin due to skin irritation such as photodynamic substances and exacerbation of allergic contact dermatitis.

As a treatment method for such pigmentation, in general, in Japan, a substance that suppresses the production of melanin, such as vitamin C, vitamin E, glutathione, etc., or external use of vitamin C, cysteine, etc., is generally used. It is taken.
In Europe and America, hydroquinone preparations are used as medicines.

Further, as crude drugs, extracts such as singly, fresh, river, aloe, pollen, gardenia, mulberry bark, soybean, soybean, roots, cucurbitaceae, etc. (JP-A-56-92208, JP-A-50-135236) , JP-A-57-77610, etc.) Pantethine, pantethine and their derivatives (JP-A-56-73012, JP-A-57-74052, JP-A-57-74052)
58-134022, JP-A-59-36606), in the context of vitamin C, 3-0-glucosyl-L-ascorbic acid, N-acyl amino acid ester ascorbic acid, 3-0-monoester ascorbic acid, hydroxypropiophenol ascorbic acid. (JP-A-59-27825, JP-A-56-135411,
JP-A-56-161314, JP-A-51-101138), kojic acid-related (JP-A-53-3538, JP-A-53-6432, JP-A-54-9263)
2, JP-A-56-7710, JP-A-56-79616, JP-A-59-3320
7), hydroquinone fatty acid ester (JP-A-57-14580)
3, JP-A-58-154507), dicarboxylic acid esters (JP-A-58-103319) and the like are known.

However, ascorbic acid has a problem in stability, it is unstable in a system containing water and causes discoloration and odor, and thiol compounds such as glutathione and cysteine have a strong offensive odor and are easily oxidized to an external preparation. Blending is avoided. Further, these compounds, except for hydroquinone, are extremely slow in their effects, so that the effects are not sufficient.

On the other hand, hydroquinone has been recognized to be effective, but it is sensitizing, the skin of Japanese people is too irritating, and allergic contact dermatitis occurs as a side effect, so its use is restricted in Japan. The formulation is also unstable. In order to improve its safety, attempts have been made to convert higher fatty acids into monoesters, but these esters are not necessarily safe because they are decomposed by a hydrolase in the body.

[Problems to be solved by the invention]

In view of such circumstances, the inventors of the present invention have earnestly studied to obtain a drug having a high safety and a truly excellent anti-pigmentation effect, and as a result, sialic acid and a sialic acid derivative are extremely safe and are sufficient. They found that they have an anti-pigmenting effect, and completed the present invention based on this finding.

[Means for solving problems]

That is, the present invention provides an anti-pigmenting agent containing one or more selected from the group consisting of sialic acid and sialic acid derivatives.

 Hereinafter, the configuration of the present invention will be described in detail.

The sialic acid used in the present invention is a known substance, and is a generic term for N-acyl and N-acyl, 0-acyl derivatives of polyhydroxymonoaminocarboxylic acid (inolaminic acid), which is also called sialic acid. Sialic acid is contained in various organisms and normally constitutes cell surface saccharides and is present as a glycosidic bond at the ends of sugar proteins and glycolipids. In particular, it is mainly present in the brain, nerves, blood, submandibular gland, mucinous substance, and colostrum, but is liberated and also present in serum, body fluids, and urine. The most representative sialic acid found in the living world is N-acetylneuraminic acid (NANA: molecular weight 309), melting point 185-187 ° C, ▲
[Α] ²⁰ _D ▼ -32 ° ± 2 ° white powder.

The biological pharmacological effects of sialic acid and sialic acid derivatives are known to contribute to the negative charge on the cell surface, involve in the specific recognition mechanism of cells, reduce hemagglutination by viruses, and reduce homing of blood proteins. ing. Recently, with regard to sialic acid, expectorant activity (JP-A-61-6841
8), anti-inflammatory effect (JP-A-62-145015) and nutritional effect of sialic acid-linked oligosaccharide (JP-A-61-152233).

However, it is still unknown to have an antipigmenting effect.

Pigmentation referred to here is sporadic ovale, liver spot, melasma,
Senile pigmented spots, petaloid pigmentation, actinic keratosis, pigmented nevus, nevus of Ota, Bellrock dermatitis and others, pigmentation after inflammation, pigmentation due to sunburn, etc. Symptoms of or near deposition.

The production method of sialic acid and sialic acid derivatives is a synthetic method,
Natural extraction method (raw material, egg white, submandibular gland mucin, placenta extract,
Colominic acid and the like obtained from E. coli)
The milk raw material extraction method (Patent No. 1191212, Patent No. 125)
3988, JP-A-59-184197, etc.) is particularly preferable.

The production examples of the compound according to the present invention by the milk extraction method are shown below. Milk used in the milk extraction method can be appropriately selected from cow milk, sheep milk, breast milk (human), and the like. Further, since the sialic acid content concentration can be freely controlled depending on the degree of purification, it may be purified according to the usage, application, dosage form and other purposes. The manufacturing method is not limited to this.

(Production Example 1) Sialic acid To 10 t of cheese whey, 28 kg of hydrochloric acid was added to adjust pH to 2, and then the mixture was heated at 92 ° C for 60 minutes for hydrolysis. The obtained whey hydrolyzate was heated with a screw decanter to remove proteins coagulated by heating to obtain a sialic acid-containing liquid. Then, the sialic acid-containing liquid was placed in a desalting tank of an electrodialysis device to desalt to a conductivity of 2 mS / cm, and then dialysis was stopped once and the concentration tank liquid was discarded. Then distilled water in the concentration tank
30 was added and the dialysis was performed again to a conductivity of 50 μS / cm. After the completion of dialysis, the concentration tank liquid was concentrated and dried to obtain 600 g of a white powder. The free sialic acid purity of the powder thus obtained was about 97%.

(Production Example 2) sialic acid salt The above-mentioned free sialic acid was adjusted with caustic soda to prepare sialic acid.
Get Na. In addition, Mg salt, K salt, phosphate, amino acid salt, amino salt and the like can be freely produced according to the purpose.

(Production Example 3) Sialic acid-bound oligosaccharide The filtrate prepared by ultrafiltration of milk or cheese whey was concentrated under reduced pressure to a total solid content of 20%. 25 kg of this solution was electrodialyzed until the electric conductivity reached 20 μS / cm, and then passed through a column packed with Dowex 1 × 2 (2 kg) to adsorb oligosaccharides. Next, 20 kg of water was passed through this column to remove the neutral sugar, and then 0.5 M hydrochloric acid was passed through to elute the oligosaccharide adsorbed on the column. The pH of the obtained eluate was adjusted to pH 7.0 with 30% caustic soda, and electrodialysis was performed again until the electric conductivity reached 150 μS / cm. The obtained dialysate was concentrated and dried to obtain 100 g of white powder. The powder thus obtained had a sialic acid-linked oligosaccharide purity of 90%.

(Production Example 4) Sialic acid binding protein Rennet gazein curd waste liquid 300 was sterilized by heating in a Fordora tank at 75 ° C for 30 minutes, then cooled to 40 ° C, and the pH was adjusted to 4.6 with concentrated hydrochloric acid. After allowing the solution to stand for about 30 minutes to form a precipitate and passing the solution through a clarifier to return the pH to 7.0, the clear solution was concentrated and desalted with an RO membrane. After concentrating up to 10 times, water was added to the concentrated solution to concentrate up to 10 times again. The obtained concentrated liquid was dried to obtain 1.3 Kg of white powder. The sialic acid-binding protein of the powder thus obtained has a purity of about 80%.
there were.

(Production Example 5) Chloroform-methanol mixture (1: 1) was added to 15 kg of sialic acid-bound lipid buttermilk powder, and the mixture was stirred at room temperature for 30 minutes for extraction. Next, the chloroform-methanol mixed solution was collected and passed through an ion exchange resin (DEAE-Toyopearl acetate type) 1 to adsorb the sialic acid-bound lipid, and then the resin was washed with the chloroform-methanol mixed solution (1: 1) 2 and then 0.5 The sialic acid-bound lipid was eluted with M sodium acetate-methanol solution 4. After concentrating the eluate to remove methanol, water 5
Was added to carry out desalting and concentration of sialic acid-bound lipid by ultrafiltration. After the concentrated solution containing sialic acid-bonded lipid was evaporated to dryness with an evaporator, it was passed through a silica gel column (4.0 x 50 cm) to adsorb the sialic acid-bonded lipid, and then chloroform 1
Then, the mixture was sequentially washed with a chloroform-methanol mixed solution (4: 1) 1 and then a sialic acid-bonded lipid was eluted with a mixed solution 2 of chloroform-methanol (2: 8). The eluate was evaporated to dryness with an evaporator to obtain 15 g of a white powder.

The purity of the sialic acid-bound lipid in the powder thus obtained was 90% or more by thin layer chromatography (resorcinol method).

Next, the safety test of sialic acid and sialic acid derivatives was conducted, and the results are shown.

Acute toxicity test Each of the sialic acid, Na sialic acid, sialic acid-binding oligosaccharide, sialic acid-binding protein, and sialic acid-binding lipid produced in Production Examples 1 to 5 was used as a test substance, and ICR female mice (6 weeks old,
(1 group 5 animals), intraperitoneal administration was carried out by suspending 0.5% sodium carboxymethylcellulose / physiological saline solution to 2% by weight of each test substance using a 22 1/2 G injection needle. In addition, oral administration was carried out by suspending 5% by weight of each test substance in olive oil using an oral needle.
Intraperitoneal administration (60 ml / kg) and oral administration (30 ml / kg) were given. As a result, no deaths, weight loss, or notable poisoning symptoms were not observed during the 7-day observation period for all test substances, and no abnormality was observed in the autopsy performed on the 7th day.

As is clear from this result, the acute toxicity value (LD ₅₀ ) of sialic acid and sialic acid derivative was 1200 mg after intraperitoneal administration.
/ kg or more and 1500 mg / kg or more by oral administration, it was proved to be highly safe.

Next, the pharmacological effects of sialic acid and sialic acid derivatives were tested, and the results are shown.

(Pharmacological effect) (1) Anti-pigmentation effect and side effects Using MOP-treated phototoxic pigmentation Weiser Maple GP,
50μ sample on the shaved back once a day for about 4cm ²
It is applied to the range for 8 weeks, and the degree of anti-pigmentation effect and pigmentation appearing as a side effect are shown by a 4-point evaluation method (+ is a decolorizing effect, − is a side effect). The samples used were 5% hydroquinone (abbreviated as HQ), Na sialic acid (Production Example 2), sialic acid-conjugated oligosaccharide (Production Example 3), and sialic acid-conjugated protein (Production Example 4) dissolved in PG. .

As is clear from the results shown in Table 2, sialic acid and sialic acid derivatives have no side effects and are excellent in anti-pigmentation effect.

(Formulation) Next, formulation for applying sialic acid and a sialic acid derivative as an anti-pigmenting agent will be described. The antipigmenting agent of the present invention is used as a mixture of sialic acid and a sialic acid derivative with a pharmaceutically acceptable base and other drugs. In particular, the combined use of an ultraviolet absorber for the purpose of blocking ultraviolet rays is more effective in preventing and treating pigmentation.

Examples of the base include excipients such as lactose, starch, calcium carbonate, magnesium aluminate metasilicate, magnesium aluminum hydroxide, calcium hydrogen phosphate, sugar, lactose, aluminum silicate, and microcrystalline cellulose. Binders such as carboxymethylcellulose, polyvinylpyrrolidone, gum arabic, gelatin, sodium alginate, hydroxypropyl starch. talc,
Lubricants such as stearic acid, calcium stearate, magnesium stearate and zinc stearate, and moisturizers such as glycerin, propylene glycol and sorbitol.
Disintegrants such as agar, silicic acid anhydride, and carboxydimethylcellulose calcium. Other examples include surfactants, buffers, preservatives, fragrances, dyes, oils, pigments, water, alcohols, thickeners, preservatives, antioxidants, chelating agents, etc., and these may be used alone or in combination of two or more. Used. However, it is not limited to these.

The above-mentioned drugs include skin nutrition agents, hair nutrition agents, enzymes,
Examples include current whitening agents.

For example, iodotyrosine and its derivatives, methionine, lysine, amino acids such as serine and their derivatives,
Vitamin A, pantothenic acid, biotin, vitamin B ₂ , vitamin B ₆ , nicotinic acid, vitamin C, vitamin E, vitamin F and vitamin derivatives such as these, female hormones, pituitary hormones, enzymes such as enzyme phosphorylase, and Examples include hormones, other inositol, orotic acid, thioctic acid, chondroitone sulfate, hyaluronic acid, etc., but are not limited thereto.

As the above-mentioned ultraviolet absorber, benzoic acid para-aminobenzoic acid (hereinafter, abbreviated as PABA), PABA monoglycerin diester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N- Dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA amyl ester, N, N-dimethyl PABA octyl ester and the like. The anthranilic acid type is homomenthyl-N-astylanthranilate and the like. The salicylic acid type includes amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate and the like. The cinnamic acid type is octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-
Diisopropylcinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octylmethoxycinnamate, 2-ethoxyethyl-p-4-
Cinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glycerinneno-2-ethylhexanoyl-diparamethoxycinnamate etc. In the benzophenone system, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2 ', 4,
4'-Tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4
-Methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenylbenzophenone-2-carboxylate, 2-hydroxy-4- n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone and the like. Other UV absorbers include 3- (4'methylbenzylidene) -d, 1-camphor and 3-benzylidene-
d, 1-camphor, urocanic acid, ethiether urocanic acid, 2-phenyl-5-methylbenzoxazole,
2,2'-dihydroxy-5-methylphenylbenzotriazole, 2- (2'-hydroxy-5'-t-octyl-phenyl) benzotriazole, 2- (2'-hydroxy-5'-methyl-phenyl) benzo Trialol, dibenzalazine, dianisoylmethane, 4-tomex-4'-t-butyl-dibenzoylmethane, 5- (3,
3'-dimethyl-2-t-norbornylidene) -3-pentan-2-one, benzalphthalide and the like can be mentioned. However, it is not limited to these.

The dosage form of the present invention can be used in any form that is suitable for ordinary medicinal products, quasi drugs, cosmetics, etc., as long as it is suitable for obtaining a medicinal effect as an anti-pigmenting agent, for example, lotion, liniment, aqueous solution. , External liquids such as emulsions, powders, solid external preparations such as dissolving tablets, and semisolid external preparations such as cream, film type, ointment, pasta, jelly, soaps, powders, granules, powders, cleansing products, capsules, syrups , Suppositories, injections and the like.

In the antipigmenting agent of the present invention, the total amount of sialic acid or sialic acid derivative as an active ingredient is 0.0001 to 50% by weight, preferably
It is 0.001 to 5% by weight. If 0.0001 to 50% by weight is blended, the effect is sufficient, and if it is blended further, the effect may not be enhanced. If it is less than 0.0001% by weight, the sufficient effect may not be obtained.

(Administration Method and Dosage) The antipigmenting agent of the present invention is mainly for transdermal administration by direct application to the affected area, but other methods such as oral administration, subcutaneous administration, intravenous administration, intramuscular administration and body cavity administration There are things to take.

The dose of the anti-pigmentation agent of the present invention may be affected by age, individual difference, medical condition, etc., so depending on the case or purpose of use, it may occur when an amount outside the following range is administered, but generally, Oral administration and transdermal dose of sialic acid or sialic acid derivative is 1kg body weight, 0.0001-2,000m per day
g, preferably about 0.01 to 200 mg, is administered to the affected area several times a day. However, it is not limited to this.

[Action]

Next, in order to clarify the anti-pigmentation effect of the sialic acid and the sialic acid derivative used in the present invention, the following practical use test was conducted.

(Test method) Twenty test subjects having pigmentation on the face were divided into 4 groups with 5 test subjects in each group, and each test substance was used in each group.

The test substances were Examples 1 to 3 and Comparative Example 1 containing no drug, and each test substance was used 2 ml twice a day (morning and evening) on the face, and after continuous use for 3 months, before use with the naked eye. The lightening effect after use was judged in four stages as compared with the above.

As is clear from the above results, sialic acid and sialic acid derivatives are highly safe anti-pigmenting agents without side effects. Further, when two or more kinds are combined, a synergistic effect is obtained, and it is effective for the treatment of preventing and treating pigmentation. It can also be used to prevent sunburn and promote recovery.

〔Example〕

Next, the present invention will be described in more detail with reference to examples. The present invention is not limited to this.

 The blending amount is% by weight.

Example 4 (wt%) 95% Ethanol 10.0 Polyoxyethylene (15 moles) Oleyl alcohol ether 2.0 Olive oil 2.0 Sialic acid Na salt 0.0001 Sialic acid-binding oligosaccharide 2.0 Polyvinyl alcohol 12.0 Glycerin 3.0 Polyethylene glycol 1500 1.0 Preservatives Suitable amount Perfume Suitable Amount Ion-exchanged water Residual Example 5 (wt%) Stearic acid 6.0 Sorbitan monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monostearate 1.5 Propylene glycol 10.0 Sialic acid-binding lipid 2.0 Sialic acid-binding protein 2.0 Antiseptic Agent / Antioxidant Appropriate amount Fragrance Appropriate amount Ion-exchanged water Residual Example 6 (wt%) Stearyl alcohol 7.0 Stearic acid 2.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.5 Polyoxyethylene (25 mol) Cetyl Alco Ether 3.0 Glycerin monostearate 2.0 Sialic acid-bound oligosaccharide 10.0 Propylene glycol 5.0 Preservative / antioxidant Appropriate amount Perfume Appropriate amount Ion-exchanged water Residual Example 7 (wt%) Solid paraffin 5.0 Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monolaurate 2.0 Soap powder 0.1 Sialic acid-bound oligosaccharide 5.0 Sialic acid-bound protein 5.0 Borax 0.2 Preservative / antioxidant Adequate amount Fragrance Deionized water Remainder Example 8 (% by weight) Stearic acid 2.5 Cetyl alcohol 2.0 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate ester 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 Ca sialic acid salt 0.1 Preservative / antioxidant Agent Suitable amount Perfume Suitable amount Ion-exchanged water Residual Example 9 (wt%) Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2.0 Polyoxyethylene (20 mol) monooleate ester 1.0 Glycerin monostearate ester 0.2 Sialic acid oligosaccharide 0.2 Quinceseed extract (5% aqueous solution) 20.0 Propylene glycol 5.0 Ethyl alcohol 10.0 Preservative / antioxidant Appropriate amount Perfume Appropriate amount Ion-exchanged water Residue Example 10 (wt%) Microcrystalline wax 1.0 Beeswax 2.0 Lanolin 2.0 Liquid paraffin 20.0 Squalane 10.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) Sorbitan monooleate 4.0 Sialic acid-binding protein 0.05 Preservative / antioxidant Appropriate amount Perfume Appropriate amount Ion-exchanged water Residual Example 11 (wt%) 95 % Ethanol 25.0 Lioxyethylene (40 mol) Hydrogenated castor oil ether 4.0 Sialic acid-bound oligosaccharide 20.0 Dipropylene glycol 15.0 Glycerin 5.0 Sodium hexametaphosphate Suitable amount UV absorber Suitable amount Preservative / antioxidant Suitable amount Perfume Suitable amount Ion-exchanged water Residual Example 12 (wt%) 95% Ethanol 10.0 Dipropylene glycol 15.0 Sialic acid-bound oligosaccharide 1.0 Polyoxyethylene (15 mol) Oleyl alcohol 5.0 Carboxyvinyl polymer (trade name: Carboball 941) 1.0 Caustic soda 0.15 L-Arginine 0.1 UV light Absorbent Adequate preservative / antioxidant Adequate amount Perfume Adequate amount Ion-exchanged water Residual Example 13 (wt%) Stearic acid 5.0 Stearyl alcohol 4.0 Stearic acid butyl alcohol ester 8.0 Glycerin monostearate ester 2.0 Sialic acid binding lipid 1.0 Zipropi Glycol 20.0 Caustic potash 0.2 Preservative / antioxidant Appropriate amount Perfume Appropriate amount Ion-exchanged water Residual Example 14 (wt%) 95% Ethanol 2.0 Preservative Appropriate amount Perfume Appropriate amount Olive oil 2.0 Sialic acid K salt 0.0001 Sialic acid Mg salt 0.5 Propylene glycol 7.0 Zinc white 25.0 Kaolin 20.0 Ion-exchanged water Residual Example 15 Tablets Tablets containing 100 mg of sialic acid Na salt and 100 mg of microcrystalline cellulose were prepared according to a conventional method, and sugar-coated with syrup gelatin precipitated calcium carbonate. It was The tablets are used in a single dose of 1 to 10 tablets.

Example 16 Granules 20 g of sialic acid-bound oligosaccharides, 80 g of lactose, 10 g of water and 90 g of microcrystalline cellulose were uniformly mixed, crushed and granulated, dried and sieved to obtain granules. This granule has a dosage of 0.5-1
Used in 0g.

Example 17 Capsule A sialic acid-binding protein (100 mg), microcrystalline cellulose (100 mg) and lactose (200 mg) were uniformly mixed. This capsule is used in a single dose of 1 to 10 capsules.

Example 18 Ointment Plastibase 50W consisting of liquid paraffin (95%) and polyethylene (5%), 47.5 g, and sialic acid-bound lipid 2.
5 g was kneaded and degassed under reduced pressure to obtain 50.0 g of ointment. This ointment is applied to the affected area 4 to 5 times a day.

〔The invention's effect〕

As can be seen from the above experiment, sialic acid and sialic acid derivatives are anti-pigmentation preventive and therapeutic agents that are highly effective in anti-pigmentation disease and have high safety and long-term continuous use without side effects. Furthermore, it is also effective in preventing sunburn, promoting recovery, and pigmentation due to sunburn.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Yukio Togawa 157 Idogaya Yanaka-cho, Minami-ku, Yokohama, Kanagawa 703 Diamond Palace Idogaya 703 (72) Inventor Kenkichi Ahiko 2-688-18 Hanakoganei, Kodaira-shi, Tokyo ( 72) Inventor Eiji Eike 2-23-5 Irumagawa, Sayama-shi, Saitama 102 (56) Reference JP-A-62-145015 (JP, A)

Claims (4)

(57) [Claims] 1. An anti-pigmenting agent containing one or more selected from the group consisting of sialic acid and sialic acid derivatives. 2. A sialic acid derivative is a sialic acid-linked oligosaccharide,
The antipigmenting agent according to claim 1, which is a sialic acid-binding protein, a sialic acid-binding lipid or a sialic acid salt. 3. The antipigmenting agent according to claim 1, which uses sialic acid or a sialic acid derivative obtained by extraction from milk. 4. The sialic acid is N-acetylneuraminic acid. Claims (1), (2) or (3).
Anti-pigmenting agent according to item