JP3106408B2 - Glucosylated kojic acid and composition containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Industrial applications]

The present invention relates to a novel glucosylated kojic acid and a composition containing the same.

[0003]

[Prior art]

[0004] Kojic acid is obtained from Aspergillus oryzae.
5-oxy-2-oxymethyl-γ-pyrone produced from various carbohydrates by Aspergillus oryzae or the like, and isolated as colorless columnar crystals having a melting point of 152 ° C.

In the past, reagents for analysis were the main use of kojic acid, but it was presumed that the hands of people involved in the brewing industry were fairly affected by kojic acid. Began to be considered.

In recent years, the discoloration preventing function of kojic acid has been used in the food field, and it is expected that various properties such as antioxidant function and antibacterial property will be used in the future.

[0007] Recently, whitening cosmetics have been commercialized utilizing the melanin production inhibiting function of kojic acid.

[0008]

[Problems to be solved by the invention]

However, kojic acid has problems in its properties such as extremely low stability against light and heat, and extremely low solubility in various solvents such as water, and improvements have been desired. .

[0010]

[Means for Solving the Problems]

The present inventors have conducted intensive studies to solve the above problems, and as a result, have succeeded in obtaining a novel glucosylated kojic acid by glucosylating any one hydroxyl group of kojic acid. By this, we succeeded in greatly improving the stability to light and heat and the solubility in various solvents such as water, succeeded in obtaining various compositions containing the glucosylated kojic acid, and completed the present invention. I came to.

That is, the compound of the present invention and the composition of the present invention containing the compound are glucosylated kojic acid obtained by glucosylating one of phenolic hydroxyl group and alcoholic hydroxyl group of kojic acid. And a composition containing the same as an active ingredient, and are as follows.

First, a compound represented by the formula (8).

[0014]

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Second, a compound represented by the formula (12).

[0016]

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Third, a compound represented by the formula (7).

[0018]

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Fourth, the compound represented by the formula (6).

[0020]

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Fifth, the compound represented by the formula (11).

[0022]

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Sixth, the compound represented by the formula (5).

[0024]

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Seventh, a cosmetic composition comprising, as an active ingredient, one or two or more glucosylated kojic acids selected from the first to sixth compounds.

Eighthly, a food or drink composition comprising as an active ingredient one or more glucosylated kojic acid compounds selected from the first to sixth compound groups.

Ninth, a pharmaceutical composition comprising, as an active ingredient, one or two or more glucosylated kojic acids selected from the first to sixth compounds.

Tenthly, there is provided a quality improver composition comprising, as an active ingredient, one or more glucosylated kojic acid compounds selected from the first to sixth compound groups.

In the present invention, the kojic acid glucosylated product represented by the formulas 8, 12, 7, 6, 11 or 5 is produced by a biochemical method regardless of the production method. May also be an organic chemistry technique.

However, in general, from the viewpoint of safety and economy, glycosyltransferase or glycosyltransferase is added to a solution containing kojic acid and / or glucosylated kojic acid and a glucosyl sugar compound as raw material substrates. Biochemical methods of reacting enzymes with other enzymes are desirable, while organic regioselectivity, non-natural binding modes, and high purity reaction products are desirable in the interest of organic chemicals. An approach is desirable.

Normally, it is desirable to produce a single type of glucosylated kojic acid by an organic chemical technique or a biochemical technique. However, if necessary, various kinds of organic and biochemical techniques can be used. A mixture of a kojic acid glucosylated product and a kojic acid glycosylated product having a glucosyl sugar compound group of various sizes bonded thereto can also be produced.

The glucosyl sugar compound used in the present invention can be obtained by converting the kojic acid having a glucosyl residue bonded to the kojic acid in an equimolar or more amount depending on the conditions of the employed organic chemical technique and the glycosyltransferase employed in the employed biochemical technique. What is necessary is just to be able to produce a glucosylated product and / or a glycosylated product,
For example, glucose, maltose, maltotriose,
Malto-oligosaccharides such as maltotetraose, maltopentaose, maltohexaose, maltoheptaose, and maltooctaose, cyclodextrin, partially hydrolyzed starch, and the like, and those modified with a protecting group can be appropriately selected.

For example, in the case of using kojic acid as a raw material and obtaining a monoglucosylated product of kojic acid as a product as a reaction condition of an organic chemical technique, a glucose derivative can be advantageously used as a glucosyl sugar compound. .

When it is desired to use kojic acid as a raw material and obtain a maltosylated product of kojic acid as a product,
Maltose derivatives can be advantageously used, and if kotoic acid is used as a raw material and maltopentaosylated product of kojic acid is desired to be obtained as a product, maltopentaose can be advantageously used. A glucosyl sugar compound corresponding to a glucosyl group or a glycosyl group of a kojic acid glucosylated product or a kojic acid glycosylated product is preferably used.

When using biochemical techniques, for example, Pseudomonas saccharophila or Pseudomonas saccharophila can be used as a glycosyltransferase.
When a maltooligosaccharide-forming enzyme derived from Stutzeri (Psuedomonas stutzeri) is used, monoglucosylated kojic acid is used as a raw material, and maltotetraose, maltopentaose, maltohexaose, and maltoheptaose are used as glucosyl sugar compounds. , Malto-oligosaccharides such as maltooctaose, or mixtures thereof, cyclodextrin, partially hydrolyzed starch and the like are advantageously used.

Next, a biochemical method for obtaining the compound of the present invention will be described.

Kojic acid used as a raw material during the reaction and / or
Alternatively, the concentration of the glucosylated kojic acid may be usually 1% by weight or more, preferably about 2% to 20% by weight, and the concentration of the glucosyl sugar compound may be kojic acid and / or
Or about 1 to 1 for glucosylated kojic acid
A range of 0 times is preferred.

The enzyme employed in the present invention is kojic acid and / or
Alternatively, when acting on a solution containing a glucosylated product of kojic acid and a glucosyl sugar compound suitable for this enzyme, the glucosylated product of kojic acid and / or kojic acid is not decomposed, and one of the hydroxyl groups of kojic acid or A glucosyl sugar compound is placed at position 4 of the glucosyl residue bound to kojic acid.
Any substance that transfers glucosylated and / or glycosylated kojic acid by transferring several or more of them may be used.

For example, maltotriose-forming enzymes derived from Streptomyces griseus and Bacillus subtilis, and Pseudomonas suttsueri.
tutzeri), Pseudomonas saccharophila (Pseud)
omonas saccharophila), maltohexaose-forming enzyme derived from Bacillus circulans and the like, Bacillus licheniformis (Bacillus li)
cheniformis), Bacillus
subtilis), Bacillus cereus
Derived maltopentaose-forming enzyme, Klebsiella pneumoniae, Bacillus subtilis, Bacillus circulans F-2, Bacillus circulans G-6 -6
) -Derived maltohexaose-forming enzyme and the like can be advantageously used.

The enzyme used in the present invention can be used in the reaction regardless of whether it is immobilized or immobilized. The reaction may be performed in a batch type or a continuous type. Can be.

As long as the above-mentioned transferase satisfies the above-mentioned conditions, the object of the present invention can usually be achieved with a crude enzyme, but if necessary, a commercially available enzyme may be used. The crude enzyme can be purified and used by a method known per se.

The pH and temperature at the time of the reaction may be within the range in which glycosyltransferase acts to produce a glucosylated kojate, and is usually selected from a range of pH 4 to 8 and a temperature of about 25 to 65 ° C. .

Although the amount of the enzyme used and the reaction time are closely related, it is usually preferable to select the amount of the enzyme so that the reaction is completed in about 1 to 48 hours from the viewpoint of economy.

When the kojic acid glucosylated product of the present invention is obtained by a biochemical method, the reaction conditions are usually adjusted so that the target substance is accumulated using the above-mentioned enzyme.
If necessary, a method of coexisting other hydrolases during the reaction to adjust the length of the glucosyl group of the once formed kojic acid glucosylate to obtain a glucosyl group of a desired size is also adopted. be able to.

Hereinafter, a typical method for obtaining kojic acid glucosylated product by an organic chemical technique will be described.

(A) Glycosylation to an alcoholic hydroxyl group (see FIG. 1)

Commercially available kojic acid (1) is acetylated with one equivalent of acetyl chloride to give monoacetate (3), and glucosylated with commercially available β-D-glucose pentaacetate (4) to give α-glucosylated product (5 ) And β-glucosylated product (6).

The α-glucosylated product (5) is deacetylated to obtain a compound (7), and the β-glucosylated product (6) is deacetylated to obtain a compound (8).

(B) Glycosylation to a phenolic hydroxyl group (see FIG. 2)

Commercially available kojic acid (1) is treated with sodium bicarbonate to form a sodium salt (9), and commercially available β-D-glucose pentaacetate (4) is glucosylated with acetobromoglucose (10) obtained by HBr treatment. To obtain a β-glucosylated product (11).

Then, (11) is deacetylated to (12)
Get.

Next, a method for purifying a kojic acid glucosylated product and / or a kojic acid glycosylated product obtained by any of the biochemical or organic chemical methods disclosed above will be described.

The glucosylated kojate or glycosylated kojate produced as described above can be purified and / or separated by applying a method known per se.

For example, crystallization technology, membrane separation technology, chromatographic separation, solvent extraction and the like can be advantageously employed as means for purifying and / or separating glucosylated kojic acid and glycosylated kojic acid. In the case of ion-exchange resin, ion-exchange fiber, zeolite, activated carbon, etc., the method can be used in any of thin layers and columns, and any of fixed bed, moving bed and simulated moving bed is adopted. Is possible.

The glucosylated kojic acid obtained by the above method is described. A glucosyl group is bonded to either the alcoholic hydroxyl group or the phenolic hydroxyl group of kojic acid, and the number of bonds is 1 to 7 in units of glucose. The glucosyl groups are bound to some degree.

Next, the properties of the glucosylated kojic acid will be described.

The novel glucosylated kojic acid compound obtained as described above has improved solubility in water and stability against heat as compared with kojic acid, and shows no residual sugar in vivo. Since there is an enzyme that hydrolyzes a group, it has excellent characteristics such as exhibiting activity even in the body, for example, in cells of the skin.

Accordingly, the glucosylated kojic acid of the present invention can be used alone or in combination with one or more other components to make cosmetics, foods and drinks, luxury goods, pharmaceuticals, antioxidants, and quality improvers. Etc. can be advantageously used.

When attention is paid to the effects of the glucosylated kojic acid of the present invention for preventing ultraviolet rays, preventing sunburn, preventing spots and freckles, various whitening cosmetics, such as creams, lotions, emulsions, packs, soaps, and shampoos. ,rinse,
It can be advantageously used in various solid, paste, and liquid products as a bath preparation, a paste, a foundation, a blusher, an eye shadow, a lotion, and the like.

For the purpose of treating pigmentation, preventing skin elastic fibrosis, antibacterial activity, antioxidation, etc., troches, liver oil drops, multivitamin preparations, mouthwashes, toothpastes, injections,
It can also be used as various medicines such as oral medicines and various nutrients.

In the field of foods, focusing on properties such as metal chelate formation, antioxidation, tyrosinase activity inhibition, and safety, for example, anti-spock agents for noodles, anti-fading agents for foods, freshness preserving agents, It can be used advantageously as a preservative for food and drink, an antioxidant for fats and oils, an anti-blackening agent for shrimp and crab, and has excellent solubility and high stability against heat and the like. Focusing on ordinary foods and drinks, for example, soy sauce, miso, furikake, sauce, noodle soup, vinegar, stew base, dashi base, complex seasoning, mirin, table sugar, curry base, rice cracker , Hail, okoshi, calinto, fertilizer, mochi, bun, uiro,
Beans, yokan, jelly, castella, candy, bread, biscuits, crackers, cookies, pies, pudding, sponge cake, chocolate, ice cream, sherbet,
It can be advantageously used for chewing gum, caramel and others.

From the various characteristics of the glucosylated kojic acid product of the present invention, meat products such as ham and sausage, fish meat ham, fish sausage, kamaboko, chikuwa, hampen and the like, and surimi which is a raw material thereof. And can also be used advantageously for frozen surimi.

Further, the glucosylated kojic acid compound of the present invention can be used in various other materials for the purpose of preventing sunburn, preventing spots and freckles, preventing oxidation, preventing discoloration, preventing rot, and preventing discoloration.
For example, it can be freely used in combination with various cosmetic raw materials, food raw materials, pharmaceutical raw materials, and the like having various pharmacological, taste, shaping, stabilizing, and increasing effects.

[0064]

【Example】

Hereinafter, referring to FIG. 1 showing a scheme of glucosylation to an alcoholic hydroxyl group, and FIG. 2 showing a scheme of glucosylation to a phenolic hydroxyl group, regarding the glucosylated kojic acid compound of the present invention. The contents of the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples.

Example-1 [kojic acid (1) → compound (2) + compound (3)]

1421.1 mg of commercially available kojic acid (1) (1
0 mmol) in 14 ml of pyridine (dry)
After cooling to -10 ° C, 0.7 ml (1 equivalent) of acetyl chloride was added, and the mixture was stirred at -10 ° C for 1 hour.

The reaction solution was filtered, concentrated under reduced pressure, and the residue was purified by passing through a column of 180 g of silica gel using a solvent of chloroform: acetone = 2: 1 to obtain Compound (2) 46.
9.5 mg (20.8% yield) and 901.9 m of compound (3)
g (49.0% yield) were obtained.

A part of the compound (2) was crystallized from ethanol.

Next, Table 1 shows the results obtained by examining the properties of the compound (2), and Table 2 shows the results obtained by examining the properties of the compound (3).

[0071]

[Table 1]

[0072]

[Table 2]

Example-2 [Compound (3) + Compound (4)
→ Compound (5) + Compound (6) + Compound (2)]

A solution of 3.73 g (20.3 mmol) of compound (3) in 90 ml of 1,2-dichloroethane (dry) and 7.92 g (20.20 g) of commercially available β-D-glucose pentaacetate (4). 3 mmol) was dissolved in 45 ml of 1,2-dichloroethane, and under a nitrogen atmosphere, 2.5 ml (20.3 mmol) of (C ₂ H ₅ ) ₂ O.BF ₃ was added. Stir for 5 hours.

Then, the reaction solution was neutralized by adding 18 ml of pyridine, and concentrated under reduced pressure.

The residue was dissolved in 1 liter of dichloromethane, washed with water, and the organic layer was dried over anhydrous MgSO ₄ .

Next, filtration was performed, the filtrate was concentrated under reduced pressure, the concentrated residue was dissolved in 50 ml of pyridine, 50 ml of acetic anhydride was added, and the mixture was stirred at room temperature overnight.

After completion of the reaction, 350 ml of dichloromethane was added, washed with water and treated with sodium bicarbonate, and the organic layer was dried over anhydrous MgSO _4.
And dried.

After removing MgSO ₄ by filtration, the mixture was concentrated under reduced pressure, and the residue was purified by passing through a 1.3 kg silica gel column using a solvent of chloroform: acetone = 10: 1 to obtain Compound (5). 0.25 g (yield 2.4%), 2.75 g (yield 26.4%) of compound (6) and 1.35 g (yield 29.5%) of compound (2) were obtained.

A part of the compound (6) was crystallized with ethanol.

Next, Table 3 shows the results obtained by examining the properties of the compound (5), and Table 4 shows the results obtained by examining the properties of the compound (6).

[0082]

[Table 3]

[0083]

[Table 4]

Example-3 [Compound (5) → Compound (7)]

372 mg of compound (5) was added to 35 ml of methanol.
Dissolved in, added 1N-NaOCH ₃ 1.7 ml, and stirred at room temperature for 1.5 hours.

The reaction solution was subjected to Amberlite IRC-50 (Am
berlite IRC-50, manufactured by Rohm and Haas) 8.5m
After filtration with celite, the residue was purified by gel filtration [Sephadex G-25 (Sephadex G-25, manufactured by Pharmacia) 300 ml, H ₂ O], lyophilized, 127.7 mg of compound (7) was obtained. (58.0% yield)

Next, the results of examining the properties of compound (7) are shown in Table 5.

[0088]

[Table 5]

Example-4 [Compound (6) → Compound (8)]

Compound (6) (3.36 g) was added to methanol 18
The mixture was dissolved in 0 ml, 1N-NaOCH ₃ 18 ml was added, and the mixture was stirred at room temperature for 1 hour.

The reaction solution was subjected to Amberlite IRC-50 (Am
berlite IRC-50, manufactured by Rohm and Haas) 90ml
After filtration with celite, concentration and crystallization gave 1.08 g of compound (8). (54.3% yield)

Next, the results of examining the properties of compound (8) are shown in Table 6.

[0093]

[Table 6]

Example-5 [Compound (9) + Compound (10)
→ Compound (11)]

A compound (9) obtained by treating a commercially available kojic acid (1) with sodium bicarbonate (8.9 g, 54.0 mmol) and a commercially available β-D-glucose pentaacetate (4) are treated with HBr. 22.1 g (54.0 mmol) of compound (10) was dissolved and mixed in 500 ml of DMF (dry), and the mixture was stirred and reacted at room temperature for 2 days.

The reaction solution was concentrated under reduced pressure, the residue was dissolved in 1 liter of dichloromethane, washed with water, and the organic layer was dried over anhydrous Mg.
And dried over SO _4.

After filtration, concentration and crystallization, compound (11) 2.
93 g (11.4% yield) were obtained.

Next, the results of examining the properties of compound (11) are shown in Table 7.

[0099]

[Table 7]

Example-6 [Compound (11) → Compound (1
2)]

Compound (11) (600 mg) was added to methanol (34).
dissolved in a mixed solvent of 34 ml of THF and 34 ml of THF.
1.7 ml of H ₃ was added and the mixture was stirred at room temperature for 2 hours.

The reaction mixture was treated with Amberlite IRC-50 (Am
berlite IRC-50, manufactured by Rohm and Haas) 17ml
After filtration with Celite, the mixture was concentrated under reduced pressure.

The residue was dissolved in methanol and crystallized to obtain 206.1 mg of compound (12). (53.3% yield)

Next, Table 8 shows the results obtained by examining the properties of the compound (12).

[0105]

[Table 8]

Example-7 [Compound (2) → kojic acid (1)]

The compound (2) (1.30 g) was treated with methanol (70 m).
It was dissolved in l, by the addition of 1N-NaOCH ₃ 12ml, and stirred for 1.5 hours at room temperature.

The reaction solution was subjected to Amberlite IRC-50 (Am
berlite IRC-50, manufactured by Rohm and Haas) 40ml
After filtration through Celite, concentration and crystallization gave 362.1 mg of kojic acid (1). (44.2% yield)

Next, Table 9 shows the results of examining the properties of kojic acid (1).

[0110]

[Table 9]

Example-8 [Preparation of glucosylated kojic acid by biochemical method]

Compound (12) 4.2 obtained in Example-6
Parts by weight were dissolved (heated) in 25 parts by weight of dimethyl sulfoxide and 25 parts by weight of a phosphate buffer (pH 7.0), and 6 parts by weight of maltopentaose was added.
While maintaining this, Pseudomonas stutzeri (
About 100 units of Pseudomonas stutzeri were added and reacted for 6 hours.

The reaction solution was prepared by using a solvent (n-butanol: acetic acid: water = 2: 1: 1) and precoated TLC plate (silica gel 60F-254, manufactured by Merck, thickness: 0.2).
As a result of analysis by thin-layer chromatography with a thickness of 5 mm and a length of 100 mm), maltopentaose appeared at a position of Rf = 0.19 and compound (12) appeared at a position of Rf = 0.59, respectively. A product obtained by adding maltopentaose to the phenolic hydroxyl group of the formed kojic acid has Rf = 0.2.
Appeared at 4.

From the size of the spot, it was determined that several percent of the raw material had been converted to this new product.

Example-9 [Example of preparation of cosmetic composition]

(Parts by weight) Compound (12) obtained in Example-6 4.1 2. Aminoacetic acid 0.2 3. Pyridoxine hydrochloride 0.05 4. Zinc phenolsulfonate 0.35. Propylene glycol 8 6. Ethanol 5 7. Purified water 82.35

A lotion as a cosmetic composition of the present invention was prepared by appropriately mixing the above 1 to 7.

Example 10 [Example of preparation of cosmetic composition]

(Parts by weight) Compound (8) obtained in Example-4 4 2. Beeswax 10 3. Ceresin 7 4. White petrolatum 3 5. Lanolin 3 6. Isopropyl myristate 3 7. Squalane 4 8. Liquid paraffin 37 9. Polyoxyethylene cetyl ether 2.7 10. Polyglycerin trilaurate 2.3 11. Propylene glycol 2 12 Purified water 21 13. Small amount of fragrance

The above 1 to 13 are appropriately dissolved and mixed, and
A cold cream as the cosmetic composition of the present invention was prepared.

Example-11 [Example of preparation of cosmetic composition]

(Parts by weight) Sodium chloride 62 2. Borax 3 3. Sodium sesquicarbonate 15 4. Sodium sulfate 5 5. Reaction product obtained by filtering the reaction solution obtained in Example-8 and removing the solvent 10 6. Borneol 0.6 7. Dextrin 3.0 8. Turpentine oil 0.4 9. Flavor small amount 10. 10. Tar dye small amount Geraniol small amount

The above-mentioned 1 to 4 are previously slurried and homogeneously mixed.

Next, a part of the homogeneous mixture of the above 1 to 4 was mixed with the above 5 to 7 and slurried.
While mixing and further mixing, the rest of the above homogeneous mixture of 1 to 4 was mixed to prepare a powdery bath agent of the present invention.

Example-12 [Preparation Example of Food and Beverage Composition]

In 220 cc of water, 70 g of sugar, 4 g of maltitol [Amalti-P (registered trademark) manufactured by Towa Kasei Kogyo KK], and 5 g of polydextrose [manufactured by Pfizer] 5
g, add to the fire, and when each has melted, 10g in advance
The gelatin which had been swollen by adding 50 cc of water to the gelatin was taken out, taken out of the fire, and completely dissolved while mixing with cooling.

Then, after cooling to 50 ° C. or less, 10 g of apple juice which had been peeled off in advance and the core was removed and grated into pulp and the reaction solution obtained in Example-8 were filtered and the solvent was removed. 0.3 g of the removed reactant was added, mixed, placed in a mold, and cooled and solidified in a refrigerator to obtain jelly as a food and drink of the present invention.

Example 13 [Preparation Example of Food and Beverage Composition]

33 g of orange juice powder, granulated sugar 6
0 g, citric anhydride 1 g, malic acid 0.1 g, ascorbic acid 0.1 g, powdered orange flavor 0.6 g, and 0.2 g of the compound (12) obtained in Example-6 were stirred and mixed, and fluidized granulation was performed. put into a machine, exhaust air temperature 35 ℃, the wind speed per minute 10m ^3,
Add 10% maltitol solution [Towa Chemical Industry Co., Ltd.]
Amalti P (registered trademark)] as a binder was sprayed at a rate of 10 ml / min, and the mixture was granulated for 30 minutes to prepare a powdered orange juice as a food and drink of the present invention.

Example-14 [Preparation Example of Pharmaceutical Composition]

(Parts by weight) Polyethylene glycol monostearate 2 2. Glycerin monostearate 5 3. Stearic acid 5 4. Behenyl alcohol 15. Liquid paraffin 10 6. Glyceryl trioctanoate 10 7. Paraoxybenzoic acid methyl ester 0.2 8.2 1,3-butylene glycol 5 9. Purified water 48.8 10. Compound (8) 3 obtained in Example-4 11. Human placenta extract solution 10

The above 1 to 7 were dissolved by heating, and the above 8 and 9 were dissolved.
Is added and mixed to form an emulsion, and then, after cooling, the above-mentioned 10 and 11 are added and mixed to prepare an ointment-1 for inhibiting melanin production, which is a pharmaceutical composition of the present invention. did.

Example-15 [Preparation example of quality improving composition]

780 g of hardened soybean oil, 80 g of milk casein,
POLYGLYCERIN FATTY ACID ESTERS [manufactured by Sakamoto Yakuhin Co., Ltd., PO
-500], 30 g, maltitol [Towa Chemical Industry Co., Ltd.]
Amarty Syrup (registered trademark)] 70% aqueous solution 2
70 g, 20 g of the compound (8) obtained in Example-4, and 1 liter of water were mixed for 5 minutes at 10,000 rpm using an emulsifier [Ultra Homomixer UM-2 manufactured by Nippon Seiki Seisakusho]. To obtain an emulsion.

Next, this was spray-dried [Okawara Kakoki Co., Ltd.
(L-8 type) to obtain a surimi additive that is a quality improving composition of the present invention.

Comparative Test-1 [Thermal Stability Test]

The novel compounds (8) and (12) of the present invention and kojic acid (1) as a comparative product were put into each screw vial in an amount of 0.15 mmol each, and water was added. To 1 g each.

At this time, the amount of the sample was Compound (8) 4
5.6 mg, compound (12) 45.6 mg, kojic acid (1) 2
1.3 mg.

The three specimens were sealed and placed in an oil bath at 70 ° C.
After heating for days, changes in color and pH and changes in purity by TLC were analyzed.

The results of the analysis are shown in Table 10.

[0141]

[Table 10]

The coloration of kojic acid (1) after heating was 3.
When diluted 5 times, the color density became almost the same as that of the compound (8). When diluted 15 times, the color density became almost the same as that of the compound (12).

A negative correlation was found between the degree of coloring and the change in purity by TLC, in which the deeper the color, the lower the purity.

Comparative test-2 [Solubility test]

The novel compounds (8) and (12) of the present invention and the kojic acid (1) of the comparative product were
In order to examine the solubility in water at 20 ° C., the relationship between the refractive index concentration [concentration indicated by a refractometer manufactured by Atago Co., Ltd.] and the concentration (% by weight) of each compound known in advance was set as a calibration curve. The concentrations of the prepared saturated aqueous solutions were determined using these calibration curves.

Table 11 shows the obtained saturated aqueous solution concentrations.

[0147]

[Table 11]

The solubility of kojic acid in water was improved for both the compounds (8) and (12) of the present invention, and a remarkable improvement was particularly observed for compound (12).

Comparative test-3 [Confirmation test of whitening effect]

The ointment-1 of the present invention obtained in Example-14
(Inventive product) and compound (8) in the compounding of Example-14
Ointment-2 (invention) using compound (12) in place of
In addition, using ointment-3 (control product) prepared in the same manner except that compound (8) was removed from the composition of Example-14, 60 men and women (30 men, arbitrarily selected) ages 25 to 45 years old, Woman 3
0) (used once a day for the back of the left hand and part of the face for three months from July to September), and a questionnaire was given on the effect of preventing spots and freckles.

Table 12 shows the results of the questionnaire.

[0152]

[Table 12]

From the results in Table 12, it can be seen that the ointment containing the glucosylated kojic acid of the present invention can be used safely with almost no occurrence of skin spots and skin irritation, and excellent stains and freckles. It can be seen that it has the effect of preventing

[0154]

【The invention's effect】

The glucosylated product of kojic acid, which is a compound of the present invention, has improved stability to light and heat, improved solubility in water, and excellent properties as compared with kojic acid. .

[0156] The products used also have excellent effects such as whitening, sterilization and antioxidation.

[Brief description of the drawings]

FIG. 1 is a diagram showing a scheme of glucosylation of a kojic acid glucosylated product, which is a compound of the present invention, to an alcoholic hydroxyl group.

FIG. 2 is a diagram showing a scheme of glucosylation of a glucosylated kojic acid compound, which is a compound of the present invention, to a phenolic hydroxyl group.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 7/48 A61K 7/48 C07H 17/04 C07H 17/04 // A61K 31/7048 A61K 31/7048 A61P 31/04 A61P 31 / 04 C12P 19/58 C12P 19/58 (C12P 19/58 C12R 1:38) (72) Inventor Kazuaki Kato 477 Nakasone, Yoshikawa-cho, Kitakatsushika-gun, Saitama (56) References JP-A-4-46191 (JP, A) J.I. CARBOHYDRATE CH EMISTRY, Vol. 6, No. 4 (1987) p. 609-618 (58) Field surveyed (Int.Cl. ⁷ , DB name) C07H 15 / 26,17 / 04 A23L 1/30 A23L 3/3544 A61K ⁷ /00-7/50 A61K 31/7048 CA (STN ) CAOLD (STN) CAPLUS (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] (1) A compound represented by the formula (8): Embedded image 2. A compound represented by the formula 12. Embedded image 3. A compound represented by the formula 6. Embedded image 4. A cosmetic composition comprising, as an active ingredient, one or two or more glucosylated kojic acids selected from the group of compounds of claims 1 to 3 . 5. A food or drink composition comprising, as an active ingredient, one or two or more glucosylated kojic acids selected from the group of compounds of claims 1 to 3 .