JP3082058B2 - 6-O-α-D-galactopyranosyl-L-ascorbic acid or salt thereof, process for producing the same, and use thereof - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an L-ascorbic acid sugar derivative having excellent stability, that is, 6-O-.alpha.-D-galactopyranosyl-L-ascorbic acid or a salt thereof, a process for producing the same and use thereof. It is about.

[0002]

2. Description of the Related Art L-Ascorbic acid (vitamin C) is synthesized from L-gulonolactone in the liver of mammals, but must be taken in as an essential vitamin in humans, monkeys and guinea pigs due to lack of synthase. There is. In vivo, L-ascorbic acid is involved in the hydroxylation of proline and lysine, which are necessary for the synthesis of collagen, which is the main component of biological connective tissue, and reduces Fe ³⁺ of cytochrome C to Fe ²⁺ . It is known to be involved in redox reactions such as oxidative reactions, as well as to prevent damage by radicals, to enhance immunity by increasing leukocytes, to prevent atherosclerosis by suppressing cholesterol production, and to prevent allergic effects by antihistamine. Play an important role in maintaining and improving the health of the population. Scurvy has long been known as a deficiency of L-ascorbic acid and has weakened skin,
It presents with petechia, ecchymosis, gingival and submedullary bleeding.
To prevent this, 50mg /
Daily L-ascorbic acid intake is considered necessary. As described above, L-ascorbic acid is used not only as a vitamin C enhancer as an essential nutrient supplier but also as a sour agent, a reducing agent, an antioxidant, a bleaching agent based on its chemical structure and physiological activity. , Various chemical reaction bases as stabilizers, food and drink, etc., as well as preventive and therapeutic agents for susceptible diseases such as viral diseases, bacterial diseases, malignant tumors, diabetes, etc. The range of application is extremely wide, including cosmetics as absorbents, skin-beautifying agents due to melanin production-suppressing action, and skin-whitening agents.
However, this L-ascorbic acid is a very unstable substance, and is known to be easily decomposed and denatured by heat, light, oxygen, metal ions and the like. Many attempts have been made to stabilize such unstable L-ascorbic acid, and some derivatives have been developed. For example, ascorbic acid phosphate (JP-A-57-1
No. 40789), glycosyl ascorbic acid (JP-B-5)
8-5920), fatty acid esters of ascorbic acid (Japanese Patent Application Laid-Open No. 62-84072), L-ascorbic acid derivatives and methods for producing the same (Japanese Patent Application Laid-Open No. 2-311490), and the like.

[0003]

As described above, various ascorbic acid derivatives have been developed. Among them, saccharide derivatives have excellent stability and are expected to be put to practical use. The yield at the time of the reaction was low, and there was a problem to be solved. The present invention provides an L-ascorbic acid sugar derivative or a salt thereof that is safe, has excellent storage stability, and can sufficiently exert the physiological activity of L-ascorbic acid in a living body, and a method for producing the same in a high yield. It is another object of the present invention to provide foods and drinks, anti-sensitivity agents and cosmetics containing the L-ascorbic acid sugar derivative as an active ingredient.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, α-galactosidase was added to a mixture of L-ascorbic acid or a salt thereof and a galactose donor. Act under mild conditions, α
It has been found that the target L-ascorbic acid sugar derivative can be synthesized in good yield by utilizing the transglycosylation reaction of -galactosidase, and the present invention has been completed.

That is, the present invention provides a compound represented by the following formula:
-O-α-D-galactopyranosyl-L-ascorbic acid or a salt thereof, and reacting α-galactosidase with a solution of L-ascorbic acid or a salt thereof and a compound containing an α-galactosyl group. 6-O-
A method for producing α-D-galactopyranosyl-L-ascorbic acid or a salt thereof, and 6-O-α-D-galactopyranosyl-L-ascorbic acid or a salt thereof as an active ingredient. Food and drink, anti-sensitivity drugs,
And cosmetics.

[0006]

Embedded image

Hereinafter, the present invention will be described in detail. The 6-O-α-D-galactopyranosyl-L-ascorbic acid according to the present invention has a structure represented by the above formula 2, and L-ascorbic acid which is a component used in pharmaceuticals, foods, cosmetics, and the like. It is composed of galactose, and when it is used as an active ingredient of the food and drink, the antisensitizing agent and the cosmetic of the present invention, for example, a salt such as a sodium salt, a potassium salt, and a lithium salt may be used.

[0008] The α-galactosidase used in the present invention, when allowed to act on a solution containing a compound containing a galactosyl group and L-ascorbic acid, is subjected to a 6-glycosylation reaction.
Any source may be used as long as it synthesizes O-α-D-galactopyranosyl-L-ascorbic acid, and the origin and type are not limited. For example, Pycnopor
us cinnabarinus), Streptococcus bovis (St
reptococcus bovis), Diplococcus pneumoniae, Mortierella vinacea, Aspergillus nigar, Escherichia coli
chia coli), Pseudomonas fluorescens (Pse
microorganisms such as udomonas fluorescens), Candida guilliermondii, Vicia sativa, green coffee beans (Gr.
Although α-galactosidase produced by plants such as een coffee bean can be used, α-galactosidase produced by Candida guilliermondii is preferred from the viewpoint of yield.

Candida guilliermond used in the present invention
ii includes ATCC6260, ATCC9058, AT
CC9390, ATCC14242, ATCC2201
7, ATCC22948, ATCC22949, ATC
C22995, ATCC26860, ATCC2887
3, ATCC 32542, ATCC 34134, ATC
C38290, ATCC42050, ATCC5682
2, IFO0437, IFO0454, IFO067
9, IFO0837, IFO0838, IFO191
3, IFO1972, H-404 (FERM FER)
MP-11026), but Candida guilliermondii H-404 in terms of reaction yield.
(FERM P-11026).

As a method for producing α-galactosidase from these microorganisms, liquid culture or solid culture is usually used. In the case of liquid culture, the culture supernatant can be used as an enzyme agent as it is in the case of solid culture. In some cases, the cells can be used as they are as an enzyme preparation. In addition, an enzyme produced by a known method can be used if necessary. These enzymes or cells producing the enzymes can be immobilized and used repeatedly in a continuous or batch-wise reaction.
If necessary, L-ascorbic acid and a compound containing an α-galactosyl group may coexist during the growth of a microorganism having an α-galactosyl group transfer reaction ability to form 6-O-α-
D-galactopyranosyl-L-ascorbic acid can also be produced.

In the present invention, L-ascorbic acid includes
It includes not only free L-ascorbic acid but also metal salts of L-ascorbic acid such as alkali metal salts or alkaline earth metal salts thereof, or mixtures thereof. The compound containing an α-galactosyl group used as a substrate for α-galactosidase may be a natural product, an organic synthesis product, or an enzyme reaction product regardless of its origin. Natural products include melibiose, manninotriose, raffinose, stachyose, verbascose, galactomannans such as guar gum and locust bean gum and mixtures thereof, and organic compounds such as phenyl-α-galactoside and paranitrophenyl- α-galactoside, orthonitrophenyl-α-galactoside, metanitrophenyl-α-galactoside, and the like, and enzymatic reaction products such as melibiose, enzymatically decomposed products of galactomannan such as guar gum and locust bean gum, or high-concentration galactose An α-galacto-oligosaccharide composition produced by reacting α-galactosidase with a lactose hydrolyzate is used.

In the present invention, the concentration of L-ascorbic acid during the reaction is suitably from 1 to 60% (W / V), preferably from 5 to 40% (W / V), and more preferably from 10 to 30%.
(W / V) is more preferred. An appropriate concentration of melibiose is 1 to 80% (W / V), and 5 to 60%
(W / V) is preferable, and 10 to 40% (W / V) is more preferable. The concentration of lactose is 1-80% (W /
V) is suitable, and 5 to 60% (W / V) is preferable,
10 to 40% (W / V) is more preferable.

The pH during the reaction is suitably from 3.5 to 8.0, but the pH may be selected according to the enzyme used.

The reaction temperature is suitably in the range of 10 to 90 ° C, preferably in the range of 30 to 80 ° C, and more preferably in the range of 40 to 70 ° C.
Is more preferable.

The reaction time is not particularly limited, but may be selected such that the amount of L-ascorbic acid sugar derivative produced is maximized.

The L-ascorbic acid sugar derivative produced by such a method is separated by a conventional separation means such as membrane separation, ion exchange column chromatography, activated carbon column chromatography, liquid chromatography, silica gel column chromatography and the like. Can be. At this time, the unreacted L-ascorbic acid and the compound containing an α-galactosyl group which are separated can be reused as a raw material for the sugar transfer reaction.

6-O-α-D-galactopyranosyl-L-ascorbic acid, which is an active ingredient of the foods and drinks, antisensitizing agents and cosmetics of the present invention, is a highly stable and safe vitamin C enhancer. Not only as a taste improver, sour agent, stabilizer, quality improver, antioxidant, ultraviolet absorber, etc.
0.001% by weight or more can be advantageously used in foods, foods, foods, feeds, prophylactics and therapeutics for susceptibility diseases, and cosmetics such as skin-skins and skin-whitening agents, depending on the purpose.

6-O-α-D-galactopyranosyl-L-ascorbic acid is in harmony with various substances having tastes such as sour, salty, astringent, umami, and bitter,
Since it has high acid resistance and heat resistance, it can be used for ordinary foods and drinks, taste foods such as synthetic liquor, fruit liquor, Western liquor, liquor such as chu-hi, tea, juice, carbonated drink, lactic acid drink, lactic acid drink, sports drink, etc. Instant drinks such as soft drinks, instant juice, instant tea, instant soup, soy sauce, powdered soy sauce, miso, powdered miso, moromi, sauce, ketchup,
Mayonnaise, dressing, lemon juice, vinegar, three tablespoons of vinegar, sushi vinegar, powdered sushi vinegar, mirin, mirin-style seasoning, tempura soup, noodle soup, Chinese ingredients, dumpling sauce, grilled meat sauce, curry roux, stew sauce, soup ingredients, Dashi mushrooms, various seasonings such as complex seasonings, salad oil, oil and fat foods such as margarine, fruit syrup pickles, syrups such as honey, butter cream, custard cream,
Spread pastes such as peanut paste, flower paste, fruit paste, jam, marmalade, syrup pickles, fruit and vegetable processed foods such as fruit,
Rice crackers, hail, okoshi, buns, uiro, mochi, bean jam, yokan, jelly, castella, candy, etc., bread, cookies, crackers, pies, biscuits,
Puddings, cakes, cream puffs, waffles, donut, chocolate, chewing gum, caramel, candy, snacks and other Western confections, ice creams, sherbet and other ice confections, bread, cooked rice and other cereal processed foods, pickles, and meat products Vitamin C enhancer, taste improver, acidulant, quality improver for bottling and canning of fish meat products, tsukudani, prepared foods, milk drinks, dairy products, livestock meat, fish meat, fruits, vegetables, etc. , A stabilizer, an antioxidant and the like. Also,
In addition to feed and feed for livestock, poultry, bees, silkworms, fish, and other raised animals, vitamin C enhancers, taste improvers, quality improvers, stabilizers, antioxidants, palatability improvement, etc. Can be blended.

In addition, lozenges, liver oil drops, multivitamin preparations, tube nutrition, oral medicines, injections, toothpaste paste, mouth freshener, mouthwash, lipstick, eyeshadow,
Formulated in lotions, foundations, milky lotions, hand creams, sun creams, facial soaps, shampoos, rinses, hair stylings and other solid, pasty, liquid tastes, cosmetics such as skin tones and whiteners Can be implemented. Furthermore, it can also be used by blending it into a plastic product or the like as an ultraviolet absorber or a deterioration inhibitor.

6-O-α-D-galactopyranosyl-L
-A disease prevented or treated by ascorbic acid is a susceptible disease in the present invention, and includes, for example, viral disease, bacterial disease, traumatic disease, immune disease, allergic disease, diabetes, cataract, malignant tumor, arteriosclerosis and the like. There may be. The form of the preventive or therapeutic agent for 6-O-α-D-galactopyranosyl-L-ascorbic acid-sensitive disease can be freely selected according to the purpose. For example, sprays, eye drops, nasal drops, gargles, liquid preparations such as injections,
Ointments, patches, pastes, powders, granules, capsules,
Solid preparations such as tablets and suppositories. In the preparation, if necessary, one or two other components such as a therapeutic agent, a physiologically active substance, an antibiotic, an auxiliary agent, a bulking agent, a stabilizer, a coloring agent, a flavoring agent, and an excipient. It is also possible to use together with the above.

6-O-α-D-galactopyranosyl-L
-The dosage of ascorbic acid can be appropriately adjusted depending on the content, administration route, administration frequency and the like. 0.0005 to 100 g per adult per day, preferably 0.0
The range is preferably from 0.5 to 50 g, more preferably from 0.01 to 10 g.

6-O-α-D-galactopyranosyl-L
-As a method for incorporating ascorbic acid, a known method such as mixing, dissolving, dipping, spraying, coating, spraying, or pouring can be appropriately selected in a process until the product is completed. Also, 6-O-α-D-galactopyranosyl-
When L-ascorbic acid is a free acid, if necessary, it is reacted with an aqueous solution of a metal hydroxide, a metal carbonate or the like to form 6-O-α-D-galactopyranosyl-L-ascorbic acid. It is also possible to prepare a substance having both vitamin C action and minerals by preparing a salt and adjusting the pH, and to use this as a nutritional enhancer, a chemical, or the like.

[0023]

Next, the present invention will be described in detail with reference to examples. Example 1 Sodium L-ascorbate (Ishizu Pharmaceutical special grade reagent) 1
After dissolving 0 g and 20 g of melibiose (manufactured by Sigma) in distilled water to make 100 ml, the pH was adjusted to 4.5. To this, 1,900 units of solution-type α-galactosidase derived from Candida guilliermondii H-404 (FERM-11026, manufactured by Micro Engineering Research Bacteria) were added, and reacted at 50 ° C for 5.5 hours. Solution α-galactosidase is Ca
ndida guilliermondii H-404 (FERM FER)
MP-11026) with 1% melibiose, 3% polypeptone, 0.5% yeast extract, 0.05% K ₂ HPO
_{4, 0.01% MgSO 4 · 7H} 2 O, 0.01% KC
of sterile liquid medium (pH 7.0) containing
By shaking culture at 30 ° C. for 4 days in a ml Sakaguchi flask, 0.8 units / ml in the supernatant and 35 units / g in the wet cells could be obtained. The activity was measured at 10 mM paranitrophenyl-α-galactoside at 0.1 mM.
2 ml and 0.2 ml of 40 mM buffer (pH conforms to the optimum pH of the enzyme) 0.05 ml of α-galactosidase solution
1M and reacted at 40 ° C. for 10 minutes.
_The reaction was stopped by adding 0.5 ml of ₂ CO ₃ and the amount of released paranitrophenol was measured by measuring the absorbance at 400 nm. 1 unit is 1 μm per minute
It was defined as the amount of enzyme that produces ole paranitrophenol.

The obtained reaction product was subjected to Bio-RAD (BIO-RAD).
) Column for high-performance liquid column chromatography AMINEX ION EXC
LUSION) HPX-87H. At this time,
0.01N H ₂ SO ₄ was used as the eluate, and the flow rate was 0.
The reaction was eluted at 6 ml / min. The detection at that time was performed with UV ₂₄₅ . As a result, 6.1 g of L-
An ascorbic acid sugar derivative was produced. At this time, the reaction yield was 30.5%.

Next, 50 ml of the above reaction product was applied to a 450 ml activated carbon column (for chromatography by Wako Pure Chemical Industries, Ltd.) and eluted with water at 10 ml / min. At this time, L-
Since the ascorbic acid and the L-ascorbic acid sugar derivative were eluted in this order, only the eluted L-ascorbic acid sugar derivative was collected and concentrated. The concentrated solution was subjected to 5 ml of an anion exchange resin Dowex 2 × 8 column (Cl ⁻
), And after passing 100 ml of distilled water at a flow rate of 1 ml / min, 100 ml of 0.04M-NaCl
Then, the target L-ascorbic acid sugar derivative was eluted. This fraction was desalted with an electrodialyzer (Micro Asilyzer manufactured by Asahi Kasei Corporation), freeze-dried, and then 2.1 g of L
-An ascorbic acid sugar derivative was obtained. The purification yield at this time was 68.8%.

The obtained L-ascorbic acid sugar derivative was analyzed by ¹³ C-NMR, and the following results were obtained. ¹³ C-NMR (σ value ppm) C-1 of galactose 101.5 Galactose C-2 71.2 Galactose C-3 71.3 Galactose C-4 72.1 Galactose C-5 72.3 Galactose C-6 of 64.0 L-ascorbic acid C-1 116.3 L-ascorbic acid C-2 180.1 L-ascorbic acid C-3 176.9 L-ascorbic acid C-4 81. 1 C-5 73.9 of L-ascorbic acid C-6 70.6 of L-ascorbic acid

The L-ascorbic acid sugar derivative obtained is hydrolyzed with α-galactosidase derived from Aspergillus niger to obtain L-ascorbic acid sugar derivative.
-Ascorbic acid and galactose formed.

From the above results, it was found that the structure of the L-ascorbic acid sugar derivative obtained above was 6-O-α-D-galactopyranosyl-L-ascorbic acid.

Example 2 Lactose (Ishizu Pharmaceutical Special Grade Reagent) (20 g) was dissolved in distilled water.
After adjusting to H6, the volume was adjusted to 80 ml. To this solution, 800 units of β-galactosidase (manufactured by Sigma) derived from Aspergillus oryzae were added, and reacted at 40 ° C. for 10 hours. After completion of the reaction, the enzyme was deactivated by boiling to obtain a lactose hydrolyzate. This is Cand
ida guilliermondii H-404 (FERM FERM FERM
P-11026) derived from 1
Add 890 units and react at 50 ° C for 16 hours.
A galactooligosaccharide composition was synthesized. Then, 15 g of sodium L-ascorbate (Ishizu Pharmaceutical special grade reagent) was added and dissolved to make 100 ml, and reacted at 50 ° C. for 5.5 hours.

Analysis by high performance liquid chromatography in the same manner as in Example 1 revealed that 9.7 g of L-ascorbic acid sugar derivative had been formed. At this time, the reaction yield was 3
2.3%.

Next, the L-ascorbic acid derivative was purified in the same manner as in Example 1 to obtain 6.7 g of the L-ascorbic acid sugar derivative. The purification yield at this time was 69.0%.

Example 3 1.7 g of raffinose pentahydrate and L-ascorbic acid 1
g containing 90 units of commercially available α-galactosidase derived from Mortierella binasse (Seikagaku Corporation) at pH 5.5.
Was prepared and reacted at 50 ° C. for 8 hours.
The reaction solution was purified according to the method of Example 1, concentrated and powdered to obtain 0.13 g of a powdery product. Next, when the structure was analyzed in the same manner as in Example 1, it was 6-O-α-D-galactopyranosyl-L-ascorbic acid.

Example 4 Stability test of 6-O-α-D-galactopyranosyl-L-ascorbic acid Using the following components, a soft drink containing grapefruit juice was obtained according to a conventional method. Ingredient% by weight Grapefruit juice 20.0 Sugar 12.0 Citric acid 1.0 6-O-α-D-galactopyranosyl-L-ascorbic acid obtained in Example 1 0.1 Water 100%

The obtained soft drink was stored at 40 ° C. for 120 days and subjected to a stability test. That is, high-performance liquid chromatography (LC-2 manufactured by Shimadzu Corporation, column: Bio-Rad AMI) is performed on vitamin C remaining in soft drink water.
(NEX HPX-87H, flow rate: 0.6 ml / min, solvent solution: 0.01 MH ₂ SO ₄ , detection wavelength: 245 nm)
Was determined. The results are shown in Table 1. The numbers in Table 1 show the residual ratio of vitamin C.

[0035]

[Table 1]

Next, the vitamin C activity test of the soft drink obtained in Example 4 was performed. That is, using a basic feed obtained by adding various vitamins other than vitamin C to skim milk powder and defatted soybean, a Hartley male guinea pig (body weight: about 250
g, 10 fish) for 20 days, and the obtained soft drink (6-O-α-D-galactopyranosyl-L-ascorbic acid concentration: 1.7 mg / ml) was orally administered at 1 ml daily. After administration, changes in body weight were measured. As a control group, 1 ml of distilled water was orally administered daily. Table 2 shows the test results. The numbers in Table 2 indicate changes in the average weight of guinea pigs.

[0037]

[Table 2]

COMPARATIVE EXAMPLE 1 Cooling was carried out in the same manner as in Example 4 except that 2-O-glycosyl-L-ascorbic acid was used instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid. Drinking water was obtained, and a stability test was performed in the same manner as in Example 4. Table 3 shows the results of the stability test.

Comparative Example 2 Cooling was carried out in the same manner as in Example 4 except that 6-O-stearyl-L-ascorbic acid was used instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid. Drinking water was obtained, and a stability test was performed in the same manner as in Example 4. Table 3 shows the results of the stability test.

Comparative Example 3 A soft drink was obtained in the same manner as in Example 4 except that L-ascorbic acid was used instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid. A stability test was performed as in Example 4. Table 3 shows the results of the stability test.

[0041]

[Table 3]

As is clear from Table 3, the soft drink containing L-ascorbic acid (Comparative Example 3) and 6-O-stearyl-L-ascorbic acid as components (Comparative Example 2) is very unstable, The amount of added vitamin C decreased with time. The soft drink containing 2-O-glycosyl-L-ascorbic acid as a component (Comparative Example 1) is relatively stable, but the stability is not so excellent as compared with the soft drink of the present invention. Was. On the other hand, the soft drink containing 6-O-α-D-galactopyranosyl-L-ascorbic acid of the present invention as a component (Example 4) has a temperature of 40 ° C.
Was also very stable over a long period of time.

[0043]

[Table 4]

As is evident from Table 4, the control group received the basal diet but did not gain much weight after day 7 due to vitamin C deficiency, and 3 out of 10 animals died after day 14 did. In contrast, the group to which the soft drink containing 6-O-α-D-galactopyranosyl-L-ascorbic acid as a component (Example 4) was administered was a soft drink containing L-ascorbic acid as a component. Similar to the group to which (Comparative Example 3) was administered, the average daily weight gain was 4 to 5 g, and no abnormality was observed during the administration period. That is, the soft drink containing 6-O-α-D-galactopyranosyl-L-ascorbic acid of the present invention as a component (Example 4) exhibits the same vitamin C activity in vivo as L-ascorbic acid. Was something.

Example 5 Antioxidant test of 6-O-α-D-galactopyranosyl-L-ascorbic acid 6-O-α-D-galactopyranosyl-L- obtained in Example 1 1 g of ascorbic acid was dissolved in 10 ml of distilled water, and the whole amount was sprayed on 100 g of fried beans and dried to obtain a bean confection.

The obtained bean confectionery was stored at 40 ° C., 5 g was weighed over time, and the solvent (chloroform: glacial acetic acid = 2:
After the extraction in 3), potassium iodide was added, the released iodine was titrated, and the increase in the peroxide value was measured to conduct an antioxidant ability test. An unsprayed bean confectionery was obtained as a control group, and an antioxidant ability test was similarly performed. Table 5 shows the test results. The numbers in Table 5 indicate peroxide values.

Comparative Example 4 The procedure of Example 5 was repeated, except that 2-O-glucosyl-L-ascorbic acid was used instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid. A bean confection was obtained, and an antioxidant ability test was performed in the same manner as in Example 5. Table 5 shows the results of the antioxidant ability test.

Comparative Example 5 A bean confection was obtained in the same manner as in Example 5 except that BHA (butylhydroxyanisole) was used instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid. The antioxidant capacity test was performed in the same manner as in Example 5. Table 5 shows the results of the antioxidant ability test.

[0049]

[Table 5]

As is apparent from Table 5, a bean confectionery sprayed with 2-O-glucosyl-L-ascorbic acid obtained by glucosylating the 2-position hydroxyl group of L-ascorbic acid, which is considered to be an antioxidant active center (Comparative Example 4) ) Showed almost the same increase in the peroxide value as the control group. On the other hand, in the soybean confectionery sprayed with 6-O-α-D-galactopyranosyl-L-ascorbic acid of the present invention (Example 5), the increase in peroxide value was suppressed to about 60% of the control group. As compared to the case where BHA known as an antioxidant was sprayed (Comparative Example 5), the increase was only about 30%, indicating a high antioxidant activity. That is, the bean confectionery sprayed with 6-O-α-D-galactopyranosyl-L-ascorbic acid of the present invention (Example 4) shows high antioxidant activity. Further, the bean confection obtained in Example 5 had the same stability and in vivo vitamin C activity as Example 4.

Example 6 Method for producing a soft drink containing grapefruit juice Using these components, a soft drink containing grapefruit juice was obtained according to a conventional method.

Example 7 Manufacturing method of chewing gum Using these components, chewing gum was obtained according to a conventional method.

Example 8 Confectionery Bread Making Method Using these components, confectionery bread was obtained according to a conventional method.

Example 9 Production of mayonnaise Using these components, mayonnaise was obtained according to a conventional method.

Example 10 Preparation of eye drops and eye irritation test The 6-O-α-D-galactopyranosyl-L-ascorbic acid obtained in Example 1 was used according to the following formulation and in a conventional manner. An eye drop was prepared. Next, the eye irritation of the eye drops of the above formulation was evaluated by a panel of 50 persons. As a result, most did not complain of irritation.

Example 11 Preparation method of toothpaste and test of storage coloring

Comparative Example 6 Toothpaste containing the same amount of L-ascorbic acid in place of 6-O-α-D-galactopyranosyl-L-ascorbic acid (Example 11) A toothpaste was prepared. Each of the toothpastes of Example 11 and Comparative Example 6 was 30
C. for 6 months, 40.degree. C. for 3 months and 50.degree. C. for 3 months, and the degree of coloring was determined according to the following criteria. -; No color +; light color ++; heavy color

Table 6 shows the results.

[0059]

[Table 6]

As is clear from Table 6, the toothpaste to which L-ascorbic acid was added (Comparative Example 6) was significantly colored, but 6-O-α-D-galactopyranosyl-L-ascorbic acid was added. The toothpaste (Example 11) showed no coloring.

Next, the toothpastes of Example 11 and Comparative Example 6 were used for 30 months in 30 patients with first-stage alveolar pyorrhea, for reddening the gingiva, eliminating the pus, improving the cecum, and improving the sway of the teeth. And its effectiveness was judged using gingival improvement as an index. During the study, the patients had the toothpaste performed twice in the morning and evening. The judgment was made every two months according to the following criteria. 5 points: Five items in the index were improved. 4 points: 4 items in the index were improved. 3 points: Three items in the index were improved. 2 points: Two items in the index were improved. 1 point: One item in the index was improved. 0 point: No improvement or deterioration. Table 7 shows the results obtained by dividing the total score of each toothpaste use group on each determination day by the number of patients.

[0062]

[Table 7]

6-O-α-D-galactopyranosyl-L
-There were no cases of worsening due to the use of ascorbic acid-containing toothpaste (Example 10),
No discomfort was recognized.

Example 13 Preparation of Oral Pasta Using 6-O-α-D-galactopyranosyl-L-ascorbic acid obtained in Example 1, oral pasta was prepared according to the following method in a conventional manner. Obtained. Ingredient Weight g Ethanol 10.0 Squalene 20.0 Precipitable silica 5.0 Polyoxyethylene hydrogenated castor oil 0.1 Sodium lauryl sulfate 0.2 EDTA calcium 0.1 Fragrance 0.6 Sorbitan monooleate 1.0 Glycyrrhizin Acid 0.1 Sodium saccharin 0.6 6-O-α-D-galactopyranosyl-L-ascorbic acid 0.5 The oral pasta obtained in Example 13 is as stable and improved as Example 11 The effect was shown.

Example 14 Preparation of Oral Lozenges The 6-O-α-D-galactopyranosyl-L-ascorbic acid obtained in Example 1 was mixed well according to the following formulation according to the conventional method. An oral troche was obtained by direct compression. Ingredient Weight g Lactose 97.0 Polyoxyethylene monostearate 0.2 Sodium lauryl sulfate 0.05 Chlorhexidine gluconate 0.02 Stevia extract 0.2 Fragrance 0.1 Hydroxyethyl cellulose 1.93 6-O-α- D-galactopyranosyl-L-ascorbic acid 0.5 The troche for oral cavity obtained in Example 14 showed the same degree of stability and improvement effect as Example 11.

Example 15 Method for Producing Mouse Wash The 6-O-α-D-galactopyranosyl-L-ascorbic acid obtained in Example 1 was mixed well according to the following formulation according to a conventional method. I got a wash. Ingredient Weight g Sorbit 10.0 Ethanol 5.0 Polyoxyethylene hydrogenated castor oil 0.1 Sucrose monopalmitate 0.2 Sodium lauryl sulfate 0.05 Saccharin sodium 0.2 Sodium bicarbonate 0.05 EDTA calcium 0.05 Fragrance 0.6 Distilled water 83.65 6-O-α-D-galactopyranosyl-L-ascorbic acid 0.1 The mouthwash obtained in Example 15 has the same level of stability and improvement effect as Example 11. showed that.

Example 16 Production Method of Creamy Cosmetic A creamy cosmetic was obtained according to a conventional method using the following components. Ingredient Weight g Squalane 25.0 Wax 5.0 Olive oil 3.0 Xanthan gum 1.0 Monoammonium glycyrrhizinate 0.3 Methylparaben 0.2 Distilled water 61.5 Fragrance Appropriate amount 6-O-α-D-galactopyranosyl − L-ascorbic acid 4.0

The above cream was applied to the faces of 20 panelists (woman) suffering from dark and black, spots, and freckles 2 times a day.
The application was applied continuously for two months, and the panelists evaluated the effect in three stages: effective, slightly effective, and ineffective. Further, instead of 6-O-α-D-galactopyranosyl-L-ascorbic acid, the same amount of L-ascorbic acid is blended,
A creamy cosmetic was obtained and tested in the same manner. The results are shown in Table 8.

[0069]

[Table 8]

Further, the above cream was stored at 40 ° C. for 6 months to examine the change of appearance and the presence or absence of unpleasant odor. Table 9 shows the experimental results.

[0071]

[Table 9]

As is clear from Tables 8 and 9, the skin cosmetic of the present invention was found to be effective in storage stability, whitening effect, and rough skin improving effect.

[0073]

The sugar derivative of L-ascorbic acid 6-O-α-D-galactopyranosyl-L-ascorbic acid or a salt thereof according to the present invention can be produced in good yield at low cost and is stable. It is non-toxic because it is easily hydrolyzed in the living body, has sufficient vitamin C activity in the living body, and has stabilizers, quality improving agents, antioxidants, bioactive agents, ultraviolet absorbers, etc. As beverages, processed foods, seasonings,
It can be advantageously used by incorporating it in foods and drinks such as favorite foods, prophylactic and therapeutic agents for susceptibility diseases, and cosmetics such as skin-beautifying agents and skin-whitening agents.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI A23L 2/02 A23L 2/02 A61K 7/00 A61K 7/00 H X 7/16 7/16 7/48 7/48 31 / 70 31/70 A61P 3/02 A61P 3/02 37/02 37/02 C09K 15/06 C09K 15/06 C12P 19/58 C12P 19/58 (72) Inventor Satoshi Kawanaka 24 Uji Kozakura, Uji City, Kyoto Prefecture (72) ) Inventor Munehiko Duho 24, Uji Kozakura 24, Uji City, Kyoto (72) Inventor Hiroshi Nakajima 24 Uji Kozakura 24, Uji City, Kyoto Prefecture (58) Fields investigated (Int.Cl. ⁷ , DB name) C07H 1/00-23 / 00 A21D 2/00-17/00 A23G 3/00-3/32 A23L 1/00-3/54 A61K 7/00-48/00 A61P 1/00-43/00 C09K 15/00-15/34 C12P 19/00-19/64 BIOSIS (DIALOG) CA (STN) REGISTRY (STN) WPI (DIALOG)

Claims (5)

(57) [Claims] 1. A 6-O-α-D-galactopyranosyl-L-ascorbic acid represented by the following formula or a salt thereof. Embedded image 2. L-ascorbic acid or a salt thereof, and α
-Solution containing a compound containing a galactosyl group and α-
The method for producing 6-O-α-D-galactopyranosyl-L-ascorbic acid or a salt thereof according to claim 1, wherein galactosidase is allowed to act. 3. A food or drink comprising the 6-O-α-D-galactopyranosyl-L-ascorbic acid according to claim 1 or a salt thereof as an active ingredient. 4. An anti-sensitive disease agent comprising 6-O-α-D-galactopyranosyl-L-ascorbic acid or a salt thereof according to claim 1 as an active ingredient. 5. A cosmetic comprising the 6-O-α-D-galactopyranosyl-L-ascorbic acid according to claim 1 or a salt thereof as an active ingredient.