JP3128780B2 - Tyrosinase activity inhibitor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tyrosinase activity inhibitor, and more particularly, it has high water solubility and
The present invention relates to a tyrosinase activity inhibitor comprising a novel kojic acid glycoside having excellent stability and improved taste as an active ingredient.

[0002]

2. Description of the Related Art Kojic acid (2-hydroxymethyl-5-)
Hydroxy-4H-pyran-4-one) has an excellent tyrosinase activity inhibitory action. For example, JP-B-61-1047, JP-A-60-137253,
JP-A-62-198372, JP-A-1-132502
As disclosed in the bulletin and the like, it has been used as a whitening agent, an anti-browning agent, a freshness preserving agent, an anthelmintic and the like.

[0003] However, kojic acid becomes unstable when kept in a solution state at a high temperature or stored for a long period of time.
It has the disadvantage that it is colored over time during the distribution process in storage and sale after storage and during use or storage after use. Therefore, in the past, various formulations have been devised so as not to impair the product value at the distribution stage at the time of formulation. Such techniques are disclosed in, for example, JP-A-61-109705, JP-A-62-108804, and JP-A-63-1.
88609, JP-A-63-270609,
JP-A-64-83008 and JP-A-3-1016
No. 09 publication.

[0004]

The coloring of kojic acid has been considerably improved by these techniques, but the formulation was difficult due to the specific conditions of the amount and the combination of the components, which made it easier to design the formulation and made it easier to design over time. It has been desired to develop a kojic acid derivative which is also stable.

[0005] In addition to kojic acid, kojic acid has a sensory drawback that taste is poor when used in foods, and foods containing a large amount of kojic acid often feel bitter. It has been desired to develop a kojic acid derivative having an improved taste.

The present applicant has found a novel kojic acid glycoside and disclosed it in Japanese Patent Application Nos. 2-150525 and 2-2682.
No. 28, Japanese Patent Application No. 2-268229, Japanese Patent Application No. 3-238
No. 418 was filed for a patent. Further, repeated tests on the properties of the kojic acid glycoside and the like were conducted, and in search of a suitable use thereof, the kojic acid glycoside had a remarkable tyrosinase activity inhibitory action, and
High water solubility, excellent stability over time, and taste when blended in food, without feeling bitterness like kojic acid, taking advantage of such properties, tyrosinase activity inhibitory action is required The inventors have found that the present invention can be applied to various uses, and have completed the present invention.

[0007]

SUMMARY OF THE INVENTION The present invention provides a useful use of a novel kojic acid glycoside having such properties. That is, according to the present invention, there is provided a tyrosinase activity inhibitor comprising the kojic acid glycoside represented by the general formula (1) as an active ingredient.

Embedded image Formula (1) (Wherein R is a hexasaccharide, a pentasaccharide, an aminosaccharide, a disaccharide, a trisaccharide)

[0008]

Kojic acid glycosides of the present invention DETAILED DESCRIPTION OF THE INVENTION, by coupling a saccharide to -CH ₂ OH group at the 2-position of kojic acid, to stabilize the koji acid acid molecules, an improvement of the taste And has a structural formula represented by the general formula (1).

Formula (1)

In the general formula (1), R is a 6-carbon sugar, 5
Hexasaccharides, aminosaccharides, disaccharides, and trisaccharides. Hexasaccharides include, for example, glucose, galactose, mannose, fructose, sorbose, and the like, and pentasaccharides include ribose, arabinose, xylose, rekryse, and xylulose. And the like.Examples of aminosaccharides include, for example, glucosamine, mannosamine, and galactosamine.Examples of disaccharides include, for example, maltose, lactose, cellobiose, and sucrose.Examples of trisaccharides include, for example, maltotriose. Cellotriose and the like.

The kojic acid glycoside of the present invention can be produced by any of a synthetic method, an enzymatic method and a culturing method, and any of them can be used. However, in consideration of productivity, economy and the like. For example, a kojic acid glycoside produced by an enzymatic method or a culture method is preferable.

In general, synthesis is carried out using a glycosyltransfer reaction of an enzyme such as amylase, phosphorylase, lysozyme or the like, or unreacted —OH group at the 1-position of a sugar is chemically bonded to kojic acid. Can be manufactured.

Next, the properties of the thus obtained kojic acid glycoside were examined. As a result, the kojic acid glycoside represented by the general formula (1) was stable and had higher water solubility than kojic acid. It turned out that the taste was significantly improved. Further, when further examined for efficacy, since it has a tyrosinase activity inhibitory effect like kojic acid,
It has been found that it can be used in various applications requiring a tyrosinase activity inhibitory effect, such as pharmaceuticals, quasi-drugs, cosmetics, and foods.

As a pharmaceutical, it has an excellent inhibitory effect on tyrosinase activity even for a therapeutic agent for pigmentation disease occurring in the dermis portion of the skin such as spots, senile lentigo, endogenous melasma, nevus, etc. Furthermore, it is useful as a quasi-drug or cosmetic, for example, as a whitening agent.

As foods, for example, they are used as anti-browning agents, freshness preserving agents, etc., which are required to suppress their tyrosinase activity, and are effective as whitening foods by making use of their good taste sensation. In addition, various uses such as an agent for preventing blackening of crustaceans and fish, an agent for keeping freshness such as fresh foods and vegetables, and an anthelmintic agent can be mentioned.

The pharmaceutical, quasi-drug, and cosmetic dosage forms containing the kojic acid glycoside of the present invention as an active ingredient include various forms that can be used externally, such as creams, ointments, emulsions, injections, and liniments. , Cataplasm, plaster,
Eye drops, pastes, lotions, emulsions, essences,
In addition to known forms such as packs, gels, lipsticks, foundations, hair shampoos, hair rinses, hair tonics, etc., various oral or solid forms such as capsules, tablets, granules, powders, syrups and drinks It is needless to say that the composition can be freely formulated and used in known forms such as preparations, and the base can be any liquid or solid raw material that is acceptable for application to the skin and hair or for internal use.

As the active ingredient, known active ingredients other than kojic acid glycoside, for example, ascorbic acid, hydroquinone, liquiritin and their derivatives, kojic acid and kojic acid derivatives, peripheral vasodilators used as fair skin agents Cepharanthin, Vitamin E, used as
Vitamin E nicotinate, nicotinic acid, nicotinamide, benzyl nicotinate, tincture tincture, pepper tincture, camphor, menthol used as a cooling agent, hinokitiol used as an antibacterial agent, benzalkonium chloride, undecylenic acid, Lysozyme chloride, glycyrrhizin, which is used as an anti-inflammatory agent,
Allantoin, one or two selected from licorice extract, various extracts derived from animals and plants, liquorice extract, garlic extract, carrot extract, ogre extract, rosemary extract, aloe extract, placenta extract, liver extract, etc. Any of the above can be appropriately selected and used freely.

At this time, if necessary, various known additives such as preservatives, fragrances, stabilizers, coloring agents, ultraviolet absorbers, antioxidants, humectants, and thickeners can be added.

The kojic acid glycoside, which is an active ingredient of the tyrosinase activity inhibitor of the present invention, may be used alone or in combination of two or more. The amount of kojic acid glycoside to be applied depends on the application site, degree of symptoms,
Although it may be appropriately changed depending on the dosage form and the like, usually about 0.01 to 50.00% by weight, preferably about 0.05 to 20.00% by weight is incorporated into the preparation.

The form in which the kojic acid glycoside of the present invention is used as a whitening food is, for example, various known forms which are generally used for eating and drinking, such as jelly, drink, jam, biscuit, candy, chocolate and the like. Can be used.

When used as an anti-browning agent and a freshness preserving agent, they are disclosed, for example, in JP-A-62-198372, JP-A-63-269942 and JP-A-1-257427. In addition, kojic acid glycoside can be used for vegetables, marine products, feeds and the like in a known manner.

In this case, if necessary, other known tyrosinase activity inhibitors which can be used as foods, such as ascorbic acid, kojic acid, etc., as well as preservatives, flavors, stabilizers, coloring agents, emulsifiers, antioxidants , Seasonings, thickeners and other known additives such as alcohol, protamine, red 2
No. 4, Yellow No. 4, BHA, carrageenan, natural flavor, β-
Carotene monoglyceride, sodium glutamate,
Sorbitol, stevia, fructose, citric acid and the like can also be added.

The amount of the kojic acid glycoside of the present invention may be appropriately changed depending on the form of the food and the like.
It is advisable to add about 1 to 10.00% by weight, preferably about 0.05 to 5.00% by weight, in the food.

As the form in which the kojic acid glycoside of the present invention is used as an anthelmintic, various known forms such as paste, solution, powder and the like can be used.

At that time, if necessary, other known anthelmintic agents,
Preservatives, fragrances, stabilizers, coloring agents, antioxidants, extenders,
Various known additives such as a thickener, for example, kojic acid, diflubenzouron, sodium dodecylbenzenesulfonate, dimethylformamide, methanol, ethanol isopropyl alcohol, polyoxyethylene nonyl phenyl ether, kaolin, and silicic acid may also be added. it can.

The amount of the kojic acid glycoside of the present invention may be appropriately changed depending on the form of the anthelmintic and the like.
About 1 to 80.00% by weight, preferably about 0.10 to 50.00% by weight may be blended in the anthelmintic.

The kojic acid glycoside to be blended may be purified in any case, but the reaction solution or culture solution may be used as it is.

Examples of the method for producing kojic acid glycoside, which is an active ingredient of the present invention, pharmaceuticals, quasi-drugs, cosmetics, foods and other examples, and test examples of the effects thereof will be described below.
They do not limit the invention in any way.

[0028]

EXAMPLES Hereinafter, specific production examples of kojic acid glycosides, prescription examples for each use, and effects thereof will be described.

Production Examples of Kojic Acid Glycoside Production Example 1 (Glutidine Kojate, Maltoside Kojic Acid) (Liquid culture method) Aspergillus albus IFO4310 strain was used as a seed bacterium, and 0.2% peptone was added to potato dextrose agar. The culture was inoculated on a slant medium (manufactured by Eiken Chemical Co., Ltd.) and cultured at 30 ° C. for one week. As seed medium, glucose 4%, corn starch 4%, peptone 0.
5%, potassium dihydrogen phosphate 0.15%, magnesium sulfate heptahydrate 0.05% and Nikkor BC-10T
X (trade name, manufactured by Nikko Chemicals Co., Ltd.) was prepared by using a 0.1% aqueous solution prepared at pH 4 and then 2,000 ml.
The flask was filled with 1,000 ml, sterilized at 121 ° C. for 15 minutes, cooled to room temperature, and inoculated with the inoculum. The culture was performed at a temperature of 32 ° C., 120 times of shaking / min, and an amplitude of
The seeds were prepared by culturing with shaking at 48 cm for 48 hours.

As a medium for the main culture, soluble starch 10
%, Peptone 0.5%, potassium dihydrogen phosphate 0.15
%, Magnesium sulfate heptahydrate 0.05% and Nikkor BC-10TX 0.1% aqueous solution adjusted to pH 4 and jar fermenter of 30 liter capacity (manufactured by Marubishi RIKEN) Fill 20 liters in each of three tanks, sterilize at 121 ° C for 15 minutes, and heat to 32 ° C.
After cooling, the inoculum was inoculated. Culture temperature 3
2 ° C., aeration rate 20 L / min and rotation speed 350-4
After culturing at 00 rpm for 120 hours, 2% of kojic acid and 10% of soluble starch were added, and culturing was further performed for 18 hours. The concentration of kojic acid glucoside in the culture solution was 1.1.
%, The concentration of kojic acid maltoside was 0.6%.

Production Example 2 (Enzymatic method) (kojic acid glucoside) 30 g of soluble starch and 9 g of kojic acid were dissolved in 200 ml of 0.05 M acetate buffer (pH 4.2), and α-amylase (mould, Sigma) After adding 12 mg, the reaction was carried out at 30 ° C. for 37 hours with stirring. The reaction was stopped by heating at 95 ° C. for 5 minutes.

The reaction mixture was passed through an activated carbon column for chromatography (manufactured by Wako Pure Chemical Industries, Ltd.) to remove most of the sugars, and then kojic acid and kojic acid glucoside were eluted with 50% ethanol. The eluate was concentrated under reduced pressure, and seeds of kojic acid were added to the syrup obtained, followed by cooling at 4 ° C. overnight for crystallization. After the precipitated kojic acid was filtered off, the filtrate was applied to a Sephadex LH-20 (Pharmacia) column, the kojic acid glucoside fraction was collected, concentrated under reduced pressure, and cooled to -4 ° C to precipitate kojic acid glucoside. After recrystallization was repeated twice, the product was freeze-dried to obtain a product. The yield was about 4 g.

Production Example 3 (Enzymatic method) (Fructoside kojic acid) 60 g of saccharose and 9 g of kojic acid were dissolved in 200 ml of 0.05 M acetate buffer (pH 4.0), and invertase (manufactured by Yeast, Wako Pure Chemical Industries) 1 After adding 0.0 ml, the reaction was carried out at 30 ° C. for 2 hours with stirring. The reaction was stopped by heating at 95 ° C. for 5 minutes. This reaction solution was treated in the same manner as in Production Example 2 to obtain a kojic acid fructoside product. The yield was about 3.5 g.

Production Example 4 (Enzymatic method) (Kojidate galactoside) 60 g of lactose and 11 g of kojic acid were dissolved in 200 ml of 0.05 M acetate buffer (pH 4.0), and 4 mg of β-galactosidase (mould, manufactured by TOYOBO) was added. After the addition, the reaction was carried out at 45 ° C. for 22 hours with stirring. 5 at 95 ° C
The reaction was stopped by heating for minutes. This reaction solution was treated in the same manner as in Production Example 2. The yield was about 8 g.

Production Example 5 (Synthesis) (Kojinoic acid mannoside) Kojic acid was added to 100 ml of a mixed solution of anhydrous acetonitrile and anhydrous N, N-dimethylformamide (1: 1).
g (3.5 mmol), 6.4 g (35 mmol) of mannose and 5 g of a strongly acidic ion exchange resin were added, and the mixture was refluxed for 24 hours with stirring. After the reaction, the filtrate was distilled off under reduced pressure by heating and filtering the strongly acidic ion exchange resin. Kojic acid mannoside was purified from the residue by an ODS column. A 7% acetonitrile aqueous solution was used as a solvent for the ODS column. The yield is 0.
36 g (34% yield).

Production Example 6 (Chemical synthesis method) (Cerotrioside kojic acid) 3 g of kojic acid was added to 150 ml of ethanol / 2.17 KOH.
g. Separately, a solution prepared by dissolving 19.1 g of α-decaacetylcellotriose bromide in 150 ml of chloroform was prepared, added to the above ethanol solution, and heated under reflux.
After 3 hours, about 800 ml of water was added, and the organic layer was extracted three times with 400 ml of chloroform. The extracted chloroform layer was washed twice with 400 ml of water, added with MgSO ₄ and left overnight to dry. After the chloroform was distilled off under reduced pressure, the dried product was recrystallized three times with 50 ml of ethanol to obtain 2.32 of white crystals.
g. The above operation was repeated five times.

Further, 0.95 g of sodium was added to 30 ml of methanol, followed by stirring and mixing in an ice bath. To this solution, a solution of 10.0 g of decetylcellotrioside kojate synthesized in the above-described manner dissolved in 70 ml of methanol was gradually added, followed by stirring. After 1 h, and neutralized with _{1N-H 2 SO 4 (pH6.5} ). After evaporating the solvent with an evaporator, 50 ml of hot ethanol was added to the dried product, and extraction was performed three times. After concentrating to 15 ml, the mixture was allowed to stand overnight at 4 ° C., and the precipitated crystals were collected by filtration to obtain 3.28 g of white crystals (cellotrioside kojate).

Stability test (test method) A 30 mM aqueous solution of various kojic acid glycosides (pH
5.0) was adjusted and left at 45 ° C. for one month, and then the degree of coloring of the solution was examined. The degree of coloration of the solution was examined by visual observation and absorbance at OD 420 nm. 30 mM kojic acid as a target
(PH 5.0) was used.

(Test Results) As shown in Table 1, after one month, no change in color tone was observed in any of the seven types of kojic acid glycosides, and no change in absorbance at OD of 420 nm was observed. On the other hand, in the kojic acid solution, coloring was observed, and OD42
The absorbance at 0 nm increased from 0.008 to 0.112.

[0040]

Solubility Test The solubility of various kojic acid glycosides in water at 20 ° C. was examined. 0.5 g of various kojic acid glycosides are placed in a test tube.
Water at 20 ° C. was added little by little in a thermostat at 0 ° C., and the amount of water that completely dissolved was determined. The results are shown in Table 2.

[0042] The solubility of various kojic acid glycosides increased about 8 to 15 times that of kojic acid.

Tyrosinase Activity Inhibition Test (Test Method) The in vitro tyrosinase activity inhibitory effect of various kojic acid glycosides used as the tyrosinase activity inhibitor of the present invention was examined. Various kojic acid glycosides were each dissolved in water as a sample solution to prepare a 40 mM solution. The enzyme solution was prepared by adding 100 mM phosphate buffer (pH 6.8) to B16 melanoma and homogenizing, followed by 30,000 G
The supernatant obtained by centrifugation was used. Enzyme solution 100 μl, 1
333 μl of 0 mM dopa solution, 100 mM phosphate buffer (pH
6.8) 542 μl and 25 μl of each sample solution were incubated at 37 ° C., and the increase in absorbance at OD 475 nM in 10 minutes was measured. The results are shown in Table 3.

[0044] As is clear from these results, the kojic acid glycoside of the present invention showed a remarkable tyrosinase activity inhibitory effect.

Sensory test : taste improvement A taste test of a 1% aqueous solution of various kojic acid glycosides was performed by 10 panelists. In the evaluation, regarding bitterness and sweetness, 5 points were scored when strongly felt, 3 points when normally felt, and 1 point when weakly felt, and their average values were measured. The results are shown in Table 4.

[0046] Various kojic acid glycosides were improved in taste.

Next, examples of useful applications of the present invention are shown by way of prescription examples. Formulation Example 1 Cream (% by weight) A Monostearic acid 2.0 Polyethylene glycol (40.EO) Self-emulsifying glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Liquid paraffin 10.0 Glyceryl trioctanoate 10 0.0B Glycerin 5.0 Ethylparaben 0.1 Kojic acid glucoside 7.0 Purified water qs The components belonging to A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. B was added to A, stirred, emulsified and then cooled to produce a cream.

Formulation Example 2 Emulsion (% by weight) Fructoside kojic acid 5.0 Maltoside kojic acid 5.0 A Polyoxyethylene monostearate 1.0 Sorbitan (20.EO) Polyoxyethylene monostearate 0.5 Sorbit ( 60.EO) Lipophilic glyceryl monostearate 1.0 Stearic acid 0.5 Behenyl alcohol 0.5 Avocado oil 4.0 Glycerin trioctanoate 4.0 B 1,3-butylene glycol 5.0 Methyl paraben 0.2 Purified water Heating and dissolving the components belonging to the appropriate amount A. Separately, the components belonging to B are dissolved by heating. A is added to B, and the active ingredients kojic acid fructoside and kojic acid maltoside are added and stirred,
After emulsification, the emulsion was cooled to produce an emulsion.

Formulation Example 3 Lotion (% by weight) Glucosamide kojic acid 5.0 Allantoin 0.1 Polyoxyethylene hydrogenated castor oil (60.EO) 8.0 Ethanol 15.0 Ethylparaben 0.1 Citric acid 0.1 Sodium citrate 0.3 1,3-butylene glycol 4.0 Disodium edetate 0.01 Appropriate amount of purified water The above components were mixed, uniformly stirred and dissolved to prepare a lotion.

Formulation Example 4 Cream pack (% by weight) Kojic acid galactoside 10.0 A Vegum 5.0 Squalane 2.0 Propylene glycol 5.0 Vitamin B ₁₂ 0.05 Purified water Appropriate amount B Zinc oxide 10.0 C Ethanol 5.0 The components belonging to A are mixed, swelled by stirring, and B is added little by little. C was gradually added thereto, and further, kojic acid galactoside was added and kneaded until a paste was obtained, thereby producing a cream pack.

Formulation Example 5 Essence (% by weight) Kojic acid glucoside 5.0 Kojic acid xyloside 2.0 1% Carboxyvinyl polymer solution 10.0 Glycerin 20.0 Hyaluronic acid 0.5 Ethanol 1.0 Purified water The above components were mixed, uniformly stirred and dissolved to produce an essence.

Formulation Example 6 Hydrophilic ointment (% by weight) Kojic acid fructoside 5.0 Kojic acid cellotrioside 2.0 Ascorbic acid 0.5 A Polyoxyethylene cetyl ether 2.0 Glyceryl monostearate 10.0 Liquid paraffin 0 Vaseline 4.0 Cetanol 5.0 B Propylene glycol 10.0 Methyl paraben 0.1 Purified water Appropriate amount The components belonging to A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. B was added to A, and the active ingredients, kojic acid fructoside, kojic acid cellotrioside, and ascorbic acid, were added, stirred, emulsified, and then cooled to produce a hydrophilic ointment.

Formulation Example 7 Aerosol (% by weight) A Kojic acid glucoside 2.0 Kojic acid glucosamide 2.0 Benzyl nicotinate 0.01 Vitamin E acetate 0.05 Cetanol 1.2 Propylene glycol 4.0 Ethanol 8.0 Purified water or 100 B Freon 123 / 141b (57:43) 7.0 A component belonging to A is mixed and dissolved and put into an aerosol container.
The container was filled with B by a conventional method to produce an aerosol.

Formulation Example 8 Poultice (weight%) Kojic acid glucoside 10.0 A Polyacrylic acid 30.0 Sorbitan monooleate 1.0 Purified water 30.7 B Sodium polyacrylate 7.0 Aluminum chloride 0.3 The components belonging to concentrated glycerin 20.0 titanium oxide 1.0 A are heated and dissolved. Separately, the components belonging to B are dissolved by heating. B was added to A, and kojic acid glucoside as an active ingredient was added, followed by stirring and mixing to produce a poultice.

Formulation Example 9 Tablet Confectionery (wt%) Citric acid 1.0 Skim milk powder 15.0 Sucrose ester 1.0 Flavor 0.8 Kojic acid glucoside 0.5 Kojic acid 0.05 Granulated sugar 20.0 Lactose 61 .65 The above-mentioned raw materials were uniformly mixed, granulated, and tableted to produce.

Formulation Example 10 Candy (% by weight) A Powdered marbit 83.0 Citric acid 0.4 Water 14.8 B Flavor 1.0 Yellow No. 4 0.001 Kojic acid fructoside 0.4 Kojic acid galactoside 0.4 A Is heated under reduced pressure with a vacuum pan to obtain a water 2
Concentrate until ~ 5%, transfer this to the cooling board,
B was successively added and cooled to about 60 ° C., which was molded by a roller or a stamping machine.

Formulation Example 11 Anthelmintic agent (% by weight) Kojic acid glucoside 10.0 Kojic acid glucosamide 10.0 Silicic anhydride 5.0 Sodium dodecylbenzenesulfonate 2.0 Kaolin 73.0 The above components are mixed and mixed. After pulverization, it was manufactured as a 20% wettable powder.

Formulation Example 12 Anthelmintic agent (% by weight) Kojic acid glucoside 5.0 Kojic acid mannoside 5.0 Dimethylformamide 40.0 Methanol 20.0 Ethanol 10.0 Isopropyl alcohol 10.0 Polyoxyethylene nonyl phenyl ether 0 The above components were uniformly mixed and dissolved to obtain an emulsion.

Crustacean Browning Prevention Eight prawns immediately after death were immersed in sterilized water at 5 ° C. for 2 minutes, and further treated with a 0.5% maltoside kojic acid aqueous solution (5%).
C.) for 2 minutes. After immersion, the shrimp were arranged on an aluminum tray and stored in a refrigerator at 4 ° C., and changes in the appearance of the shrimp were observed over time. Table 5 shows the results.

[0060] As is apparent from these results, the test in which the 0,5% maltoside kojic acid aqueous solution was immersed exhibited a superior browning prevention effect at 4 ° C. for 50 hours or more in the raw state as compared with the control test. Was done.

[0061] The diameter of the freshness action bulk one by shiitake mushrooms 10 of from 5 6 cm, sterile water (control example) were immersed for 2 minutes each in 0.5% kojic acid fructoside solution. Furthermore, 0.5% aqueous kojic acid galactoside aqueous solution was sprayed on the front and back sides of ten shiitake mushrooms. The shiitake mushrooms treated as described above were arranged in an aluminum tray, wrapped, left in a constant temperature room at 22 ° C., and changes in appearance were observed over time. The results are shown in Table 6. Sample A was a control, B was immersed in a kojic acid fructoside aqueous solution, C was a sprayed kojic acid galactoside aqueous solution,

[0062] As is clear from the results, the test group immersed in the kojic acid fructoside aqueous solution or the test group sprayed with the kojic acid galactoside aqueous solution exhibited a significantly higher freshness retention effect than the control example.

Blackening prevention action The same amount of water was added to the following composition to prepare a red sea bream bait. The above-mentioned feed was used for the kojic acid glucoside-added test group, and the same diet without kojic acid glucoside was used for the control test group. For the breeding test, 20 red sea breams (17 to 20 cm in length) were used in each test, and the color tone of the red sea bream was determined after 3 months. Feeding was performed twice a day, and 20 g / 20 tail wp was given each time. The results are shown in Table 7.

[0064]

[0065]

According to the present invention, there is provided a kojic acid glycoside having an inhibitory action on tyrosinase activity, which is highly water-soluble, has extremely good stability, and has an improved taste. When formulated in pharmaceuticals, quasi-drugs, cosmetics, foods and anthelmintics, it exhibits tyrosinase activity inhibitory action without decomposing or coloring over time, and is used to make fair-skin cosmetics and pigmentation It can be used as a remedy for skin diseases, a whitening food, an agent for keeping freshness of foods, an agent for preventing blackening of crustaceans and fish, and the like.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ identification code FI // C07H 15/26 C07H 15/26 (58) Investigated field (Int. Cl. ⁷ , DB name) A61K 31/7048 A23L 1 / 272 A61K 7/00 A61P 17/00 A61P 43/00 C07H 15/26 CA (STN) EMBASE (STN) MEDLINE (STN)

Claims (1)

(57) [Claims] 1. A tyrosinase activity inhibitor comprising, as an active ingredient, kojic acid glycoside represented by the general formula (1). Formula 1 (Wherein R is a hexasaccharide, a pentasaccharide, an aminosaccharide, a disaccharide, a trisaccharide)