JP7018693B2 - 2-O-α-D-maltosyl-L-ascorbic acid-containing composition and method for producing the same - Google Patents

Description

The present invention relates to a 2-O-α-D-maltosyl-L-ascorbic acid-containing composition having excellent moisturizing properties and skin wettability, and a method for producing the same.

2-O-α-D-glycosyl-L-ascorbic acid has the following general formula (1).

(In the formula, n indicates an integer of 1 or more.)
It has a chemical structure shown by and is decomposed into L-ascorbic acid and a sugar compound by hydrolysis. 2-O-α-D-glycosyl-L-ascorbic acid is less likely to be oxidized than L-ascorbic acid and has excellent stability, but it is easily hydrolyzed in the body and has the same physiological activity as L-ascorbic acid. Is known (Patent Documents 1 and 2), and is expected to have a wide range of applications such as cosmetics, foods and pharmaceuticals.

2-O-α-D-glycosyl-L-ascorbic acid is a compound having n of about 1 to 7 in the above general formula (1) by allowing a glycosyltransferase to act on a mixture of L-ascorbic acid and dextrin. Can be obtained as a mixture of. However, since the mixture has unfavorable properties as an applied material such as strong stickiness, 2-O-α-D-glucopyranosyl having n = 1 as a result of allowing glucoamylase to act on the mixture and purifying the mixture. Only -L-ascorbic acid has been used (Patent Document 1). On the other hand, 2-O-α-D-glucopyranosyl-L-ascorbic acid is insufficient in moisturizing property and wettability of the skin, and a compound more useful as a skin external preparation such as cosmetics has been sought.

Japanese Unexamined Patent Publication No. 03-135992 Japanese Unexamined Patent Publication No. 03-183492

It is an object of the present invention to provide a composition containing 2-O-α-D-maltosyl-L-ascorbic acid, which is non-greasy and has excellent moisturizing property and skin wettability.

As a result of diligent research, the present inventors among 2-O-α-D-glycosyl-L-ascorbic acid represented by the following general formula (1).

(In the formula, n indicates an integer of 1 or more.)
We have found that 2-O-α-D-martosyl-L-ascorbic acid, which has not been considered to be useful until now, is particularly excellent in moisturizing property and skin wettability, and completed the present invention. .. That is, the present invention is as shown below.

(1) The following general formula (1)

(In the formula, n indicates an integer of 1 or more.)
A composition containing 2-O-α-D-glycosyl-L-ascorbic acid or a salt thereof, which is represented by 70 mol% or more of the 2-O-α-D-glycosyl-L-ascorbic acid. 2-O-α-D-maltosyl-L-ascorbic acid-containing composition, characterized in that is 2-O-α-D-maltosyl-L-ascorbic acid (n = 2).
(2)
90 mol% or more of the 2-O-α-D-glycosyl-L-ascorbic acid is 2-O-α-D-maltosyl-L-ascorbic acid (n = 2). The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition according to 1).
(3)
The proportion of 2-O-α-D-glycosyl-L-ascorbic acid having n = 4 or more in the 2-O-α-D-glycosyl-L-ascorbic acid is 1 mol% or less. 2. The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition according to (1) or (2).
(4)
The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition according to any one of (1) to (3), which is a powder.
(5)
An external skin preparation containing the 2-O-α-D-maltosyl-L-ascorbic acid-containing composition according to any one of (1) to (4).
(6)
2-O-α-D-maltosyl-L-ascorbic acid or a salt thereof.
(7)
(A) The following general formula (1)

(In the formula, n indicates an integer of 1 or more.)
A step of preparing a mixture of 2-O-α-D-glycosyl-L-ascorbic acid represented by 2 and containing all of 2-O-α-D-glycosyl-L-ascorbic acid having n = 1 to 7. ,
(B) A step of allowing β-amylase to act on the mixture, and
(C) 2-O-α-, which comprises a step of purifying the mixture on which β-amylase is allowed to act to obtain a 2-O-α-D-maltosyl-L-ascorbic acid-containing composition. A method for producing a D-maltosyl-L-ascorbic acid-containing composition.

According to the present invention, it is possible to provide a 2-O-α-D-maltosyl-L-ascorbic acid-containing composition which is excellent in moisturizing property and wettability of the skin and is useful as a skin external preparation such as cosmetics.

<2-O-α-D-glycosyl-L-ascorbic acid>
In the present specification, 2-O-α-D-glycosyl-L-ascorbic acid is the following general formula (1):

(In the formula, n indicates an integer of 1 or more.)
It is one kind of 2-O-α-D-glycosyl-L-ascorbic acid represented by or a mixture thereof. N in the general formula (1) is an integer of 1 or more meaning the number of sugars (glucose) bound to the α-position of the glucose residue bound to the 2-position of L-ascorbic acid. The 2-O-α-D-glycosyl-L-ascorbic acid of the present invention is 2-O-α-D-glucopyranocil-L-ascorbic acid (n = 1), 2-O-α-D-maltosyl-L. -Ascorbic acid (n = 2), 2-O-α-D-maltotriosyl-L-ascorbic acid (n = 3), 2-O-α-D-maltotetraosyl-L-ascorbic acid (n) = 4), 2-O-α-D-maltopentaosyl-L-ascorbic acid (n = 5), 2-O-α-D-maltohexaosyl-L-ascorbic acid (n = 6), Either 2-O-α-D-maltoheptaosyl-L-ascorbic acid (n = 7) or 2-O-α-D-maltooctaosyl-L-ascorbic acid (n = 8) or It may be a mixture thereof.

The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition of the present invention means a composition containing 2-O-α-D-maltosyl-L-ascorbic acid or a salt thereof. The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition of the present invention has 2-O-α-D-glycosyl-glycosyl in the composition from the viewpoint of moisturizing property, stickiness and wettability to the skin. Of L-ascorbic acid, 50 mol% or more, 60 mol% or more, 70 mol% or more, 80 mol% or more, 90 mol% or more, 95 mol% or more are 2-O-α-D-maltosyl-L-ascorbic. It is preferably an acid. 2-O-α-D-glycosyl-L-ascorbic acid other than the composition containing 2-O-α-D-maltosyl-L-ascorbic acid is a 2-O-α-D-glucopyranocil-L-ascorbic acid ( n = 1) and / or 2-O-α-D-maltotriosyl-L-ascorbic acid (n = 3) are preferred. 2-O-α-D-glycosyl-L-ascorbic acid having n = 4 or more is preferably 10 mol% or less, 5 mol% or less, 1 mol% or less, 0.1 mol% or less, and is substantially. It is preferable not to include it.

2-O-α-D-glycosyl-L-ascorbic acid can be produced by a known method, for example, the method described in Patent Document 1.
A composition containing 2-O-α-D-maltosyl-L-ascorbic acid and substantially free of 2-O-α-D-glycosyl-L-ascorbic acid having n = 4 or more. , 2-O-α-D-glycosyl-L-ascorbic acid mixture can be obtained by reacting β-amylase.
The 2-O-α-D-maltosyl-L-ascorbic acid-containing composition of the present invention can be obtained, for example, by the following steps.
(1) Glycosyltransferase is allowed to act on a solution containing L-ascorbic acid and an α-glucopyranosyl sugar compound, and 2-O-α-D-glycosyl-L-ascorbic acid (n = 1 to 7) is mixed. A solution is obtained, and then β-amylase is allowed to act on the mixed solution to cleave the sugar chain having n = 4 or more, and 2-O-α-D-glycosyl-L-ascorbic acid (n = 1-3). Make a containing solution.
(2) Purify the 2-O-α-D-glycosyl-L-ascorbic acid (n = 1-3) -containing solution by removing unreacted L-ascorbic acid and saccharides using an ion exchange resin or the like. do.
(3) The solvent is removed to obtain powdered 2-O-α-D-glycosyl-L-ascorbic acid (n = 1 to 3).
The content ratio of 2-O-α-D-maltosyl-L-ascorbic acid can be controlled by the conditions at the time of production in step (2).

<2-O-α-D-glycosyl-L-ascorbic acid metal salt>
2-O-α-D-glycosyl-L-ascorbic acid other than 2-O-α-D-maltosyl-L-ascorbic acid and 2-O-α-D-maltosyl-L-ascorbic acid of the present invention is a salt. It may be, preferably a metal salt. By reacting 2-O-α-D-glycosyl-L-ascorbic acid with a metal salt, a metal salt of 2-O-α-D-glycosyl-L-ascorbic acid can be produced.
Metal ions of the metal salt of 2-O-α-D-glycosyl-L-ascorbic acid include alkali metals such as sodium ion and potassium ion; metal ions of group 2 elements such as magnesium ion and calcium ion; It may be a metal ion selected from the group consisting of transition metal ions such as iron ion and copper ion; and other metal ions such as zinc ion and aluminum ion, or a combination thereof.
Metal salts to react with 2-O-α-D-glycosyl-L-ascorbic acid include magnesium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium chloride, sodium chloride, potassium chloride, calcium chloride, etc. Examples thereof include magnesium sulfate, sodium sulfate, potassium sulfate, sodium nitrate, sodium carbonate, sodium hydrogencarbonate, potassium carbonate and sodium phosphate. Metal hydroxide salts such as magnesium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide are particularly preferred because the by-product of the reaction is water.

<Method for producing powder of 2-O-α-D-glycosyl-L-ascorbic acid>
By preparing a solution in which the 2-O-α-D-glycosyl-L-ascorbic acid is dissolved in a solvent and spray-drying the solution, 2-O-α-D-glycosyl-L-ascorbic acid is used. A powder of 2-O-α-D-glycosyl-L-ascorbic acid can be produced by a method including the step of powdering the acid.
As the solvent, a known solvent can be freely used as long as it dissolves 2-O-α-D-glycosyl-L-ascorbic acid, but it is preferably water and / or alcohol, and particularly preferably water. Is. Ethanol is preferable as the alcohol.
The spray drying can be performed using, for example, a spray dryer. The spray drying is preferably performed at the inlet temperature of the spray dryer of 140 to 180 ° C.
If the temperature is lower than 140 ° C., the solvent may not be sufficiently evaporated, so that a dry powder may not be obtained. On the other hand, if the temperature is higher than 180 ° C., 2-O-α-D-glycosyl-L-ascorbic acid may be decomposed or volatilized during the process. Further, it is preferable that the outlet temperature of the spray dryer is 50 to 100 ° C.

The 2-O-α-D-maltosyl-L-ascorbic acid of the present invention and the composition containing the same are excellent in surface activity and moisturizing property, low stickiness, and excellent wettability to the skin.
The 2-O-α-D-maltosyl-L-ascorbic acid of the present invention and the composition containing it can be used alone or in combination with other components as foods and drinks, external preparations for skin and the like. ..
The external skin preparation means a composition applied to the outer skin, and includes, for example, cosmetics, pharmaceuticals, and quasi-drugs. The rind includes hair and nails.
As the external skin preparation, known bases and carriers generally used in the preparation of external preparations for skin can be appropriately selected and applied according to the purpose of use, the characteristics of the preparation and the form of use.
In addition, if necessary, other components such as surfactants, skin absorption promoters, antioxidants, auxiliaries, UV absorbers, thickeners, bulking agents, stabilizers, colorants, flavoring agents, etc. It can be used in combination with preservatives, fungicides, etc.
The external skin preparation is appropriately selected as a dosage form such as an ointment, a cream, a spray, a lotion, a powder, a gel, a sol, an aerosol, a pap, a tape, etc., depending on the purpose of use and the form of use. , Can be prepared.
In the external preparation for skin of the present invention, 2-O-α- of 0.001 to 50% by weight, 0.01 to 20% by weight, preferably 0.1% by weight to 10% by weight, based on the whole external preparation for skin. Contains D-glycosyl-L-ascorbic acid. The ratio of 2-O-α-D-maltosyl-L-ascorbic acid in 2-O-α-D-glycosyl-L-ascorbic acid is preferably as described above.

The present invention will be described in more detail in the following examples, but the present invention is not limited thereto.
Other terms and concepts in the present invention are based on the meanings of terms commonly used in the art, and the various techniques used to carry out the present invention are those of particular origin. Except for this, those skilled in the art can easily and surely carry out the procedure based on known documents and the like. In addition, various analyzes were performed by applying the methods described in the analytical instruments or reagents used, the instruction manuals for the kits, catalogs, and the like mutatis mutandis.
The contents of the prior art documents, patent gazettes and patent application specifications cited in the present specification shall be referred to as the description contents of the present invention.

(Production Example 1) Preparation of powder containing 2-O-α-D-glycosyl-L-ascorbic acid (n = 1 to 3)
(1) Synthesis of 2-O-α-D-glycosyl-L-ascorbic acid 125 g of liquefied starch and 50 g of L-ascorbic acid were added to 1000 g of water and dissolved to adjust the pH to 5. To this, 20 g of a cyclomaltodexstring lucanotransferase enzyme preparation (Toruzyme 3.0L, manufactured by Novozimes) was added and reacted at 50 ° C. for 48 hours to cause 2-O-α-D-glucopyranocil-L-ascorbic acid. , 2-O-α-D-maltosyl-L-ascorbic acid, 2-O-α-D-maltotriosyl-L-ascorbic acid, 2-O-α-D-maltotetraosyl-L-ascorbic acid A reaction solution containing 2-O-α-D-glycosyl-L-ascorbic acid such as 2-O-α-D-glycosyl-L-ascorbic acid was obtained.
After inactivating the enzyme by heating the obtained reaction solution to stop the reaction, 0.7 g of β-amylase enzyme preparation (β-amylase F "Amano", manufactured by Amano Enzyme Co., Ltd.) was added. By reacting at 50 ° C. for 2 hours, 2-O-α-D-glucopyranosyl-L-ascorbic acid, 2-O-α-D-maltosyl-L-ascorbic acid, 2-O-α-D-malt A reaction solution containing triosyl-L-ascorbic acid was obtained. After the reaction, the enzyme was inactivated by heating to stop the reaction.
(2) Purification of 2-O-α-D-glycosyl-L-ascorbic acid Activated carbon was added to the obtained reaction solution for decolorization and filtration. The filtrate is passed through a column packed with an H-type cation exchange resin to remove metal ions, and then passed through a column filled with an OH-type anion exchange resin to pass 2-O-α-D-glucopyranosyl-L. -Ascorbic acid, 2-O-α-D-maltosyl-L-ascorbic acid, 2-O-α-D-maltotriosyl-L-ascorbic acid were adsorbed. The adsorbed anion exchange resin was washed with water to remove unreacted saccharides, and then 0.1N sodium hydroxide was passed through to pass 2-O-α-D-glucopyranosyl-L-ascorbic acid, 2-O. -Α-D-maltosyl-L-ascorbic acid and 2-O-α-D-maltotriosyl-L-ascorbic acid were separated and eluted. At this time, a fraction containing 2-O-α-D-maltosyl-L-ascorbic acid with high purity is recovered, and the recovered fraction is changed to obtain a purified liquid having each composition shown in Table 1 below. rice field.

(The unit of the numerical value in the table is mol%)
Further, the purified liquid of the composition containing 2-O-α-D-glycosyl-L-ascorbic acid from which metal ions have been removed by passing each purified liquid through a column filled with an H-type cation exchange resin. Got
(3) Spray drying of 2-O-α-D-glycosyl-L-ascorbic acid Each aqueous solution containing 2-O-α-D-glycosyl-L-ascorbic acid was heated and concentrated under reduced pressure to a solid content of about 15%. After that, activated carbon was added to perform decolorization and purification, and the mixture was filtered. The filtrate is spray-dried with a spray dryer (B-290, manufactured by Nippon Buch) at an inlet temperature of 160 ° C and an outlet temperature of 75 ° C to contain 2-O-α-D-glycosyl-L-ascorbic acid. The powder of the composition to be used was obtained.

(Production Example 2) Preparation of powder containing 2-O-α-D-glycosyl-L-ascorbic acid (n = 1 to 7)
(1) Synthesis of 2-O-α-D-glycosyl-L-ascorbic acid 125 g of liquefied starch and 50 g of L-ascorbic acid were added to 1000 g of water and dissolved to adjust the pH to 5. To this, 20 g of a cyclomaltodexstring lucanotransferase enzyme preparation (Toruzyme 3.0L, manufactured by Novozimes) was added and reacted at 50 ° C. for 48 hours to cause 2-O-α-D-glucopyranosyl-L-ascorbic acid. , 2-O-α-D-maltosyl-L-ascorbic acid, 2-O-α-D-maltotriosyl-L-ascorbic acid, 2-O-α-D-maltotetraosyl-L-ascorbic acid , 2-O-α-D-maltopentaosyl-L-ascorbic acid, 2-O-α-D-maltohexaosyl-L-ascorbic acid, 2-O-α-D-maltoheptaosyl- A reaction solution containing 2-O-α-D-glycosyl-L-ascorbic acid such as L-ascorbic acid was obtained.
After the reaction, the enzyme was inactivated by heating to stop the reaction.
(2) Purification of 2-O-α-D-glycosyl-L-ascorbic acid Activated carbon was added to the obtained reaction solution for decolorization and filtration. The filtrate is passed through a column packed with an H-type cation exchange resin to remove metal ions, and then passed through a column filled with an OH-type anion exchange resin to pass 2-O-α-D-glycosyl-L. -Ascorbic acid was adsorbed. After washing the adsorbed anion exchange resin with water to remove unreacted sugars, 2-O-α-D-glycosyl-L-ascorbic acid was eluted by passing 0.1 N sodium hydroxide through the solution. ..
The composition ratios of the obtained purified liquids of 2-O-α-D-glycosyl-L-ascorbic acid are shown in Table 2 below.

(The unit of the numerical value in the table is mol%)
Further, the purified liquid was passed through a column packed with an H-type cation exchange resin to obtain a purified liquid of 2-O-α-D-glycosyl-L-ascorbic acid from which metal ions had been removed.
(3) Spray drying of 2-O-α-D-glycosyl-L-ascorbic acid An aqueous solution of 2-O-α-D-glycosyl-L-ascorbic acid is heated and concentrated under reduced pressure to a solid content of about 15%, and then activated carbon is activated carbon. Was added to perform decolorization and purification, and the mixture was filtered. The filtrate is spray-dried with a spray dryer (B-290, manufactured by Nippon Buch) at an inlet temperature of 160 ° C and an outlet temperature of 75 ° C to form a powder of 2-O-α-D-glycosyl-L-ascorbic acid. Got

(Production Example 3) Preparation of 2-O-α-D-glycosyl-L-ascorbic acid potassium salt and powder thereof (1) With respect to 2-O-α-D-glycosyl-L-ascorbic acid of composition 1 described above. Then, 1 mol equivalent of potassium hydroxide was added, and the mixture was stirred at 40 ° C. for 1 hour to obtain an aqueous solution of 2-O-α-D-glycosyl-L-potassium ascorbic acid.
(2) An aqueous solution of 2-O-α-D-glycosyl-L-potassium ascorbic acid was concentrated under reduced pressure by heating to a solid content of about 15%, activated carbon was added, decolorization and purification were performed, and the mixture was filtered. The filtrate is spray-dried with a spray dryer (B-290, manufactured by Nippon Buch) at an inlet temperature of 160 ° C and an outlet temperature of 75 ° C to carry out 2-O-α-D-glycosyl-L-potassium ascorbate salt. Powder (composition 1K salt) was obtained.
Regarding 2-O-α-D-glycosyl-L-ascorbic acid of compositions 2 to 7 described above, the powder of 2-O-α-D-glycosyl-L-ascorbic acid potassium salt (composition) is the same as that of composition 1. 2-7K salt) was obtained.

(Production Example 4) Preparation of 2-O-α-D-glycosyl-L-ascorbate sodium salt and its powder Production except that 1 molar equivalent of sodium hydroxide was used instead of 1 molar equivalent of potassium hydroxide. In the same manner as in Example 3, a powder of 2-O-α-D-glycosyl-L-sodium ascorbate salt (composition 1-8Na salt) was obtained.

(Production Example 5) Preparation of 2-O-α-D-glycosium-L-ascorbic acid magnesium salt and its powder A 0.5 molar equivalent of magnesium hydroxide was used instead of 1 molar equivalent of potassium hydroxide. A powder of 2-O-α-D-glycosyl-L-magnesium ascorbic acid salt (composition 1 to 8 Mg salt) was obtained in the same manner as in Production Example 3 except for the above.

(Comparative example)
As a comparative example, composition 9: 2-O-α-D-glucopyranosyl-L-ascorbic acid, composition 9K salt: 2-O-α-D-glucopyranosyl-L-ascorbic acid potassium salt, composition 9Na salt: 2-O. -Α-D-Glucopyranocil-L-ascorbic acid sodium salt, composition 9Mg salt: 2-O-α-D-glucopyranocil-L-ascorbic acid magnesium salt, and composition 10: L-ascorbic acid were prepared.

<Evaluation of moisturizing property>
A glass bottle having a capacity of 50 ml containing 20 g of a 10% aqueous solution of each composition of compositions 1 to 10 and a metal salt thereof was placed in a desiccator having a temperature of 25 ° C. and a humidity of 35%. Was evaluated.
<Sensory evaluation>
A 10% aqueous solution of each composition was prepared and applied to the forearms of a total of 10 subjects, 5 males and 5 females aged 20 to 40 years, and 30 minutes after application, the skin was moisturized. The subjects were evaluated based on the following evaluation criteria, the scores were totaled, and then the total score was divided by 10 of the number of people to obtain the average score.
Evaluation criteria 2 points: The skin is moisturized than before application.
1 point: The skin is slightly moisturized than before application.
0 points: Same as before application.

The results are shown in Table 3 below.

(In the table, the unit of moisturizing property is mg / cm ² · hr)
As a result of the moisturizing test, the composition containing 2-O-α-D-maltosyl-L-ascorbic acid or a salt thereof (compositions 1 to 8 or a salt thereof) is 2-O-α-D-glucopyranocil-L. -It was clarified that the ascorbic acid alone has a higher moisturizing property and an excellent wettability of the skin as compared with the case of only ascorbic acid (composition 9 or a salt thereof). Surprisingly, it was found that the composition 8 or a salt thereof containing a sugar chain having n = 4 or more is inferior in moisturizing property. It was found that 2-O-α-D-maltosyl-L-ascorbic acid with n = 2 or a salt thereof is superior in moisturizing property and skin wettability to compounds having n = 1 or n = 4 or more. ..

The present invention provides 2-O-α-D-maltosyl-L-ascorbic acid, which has high moisturizing properties, is not sticky, and has excellent skin wettability, and a composition containing the same. The 2-O-α-D-maltosyl-L-ascorbic acid of the present invention is particularly useful as a skin external preparation for cosmetics and the like.

Claims (5)

The following general formula (1):

(In the formula, n indicates an integer of 1 or more.)
A composition containing 2-O-α-D-glycosyl-L-ascorbic acid or a salt thereof, which is represented by 70 mol% or more of the 2-O-α-D-glycosyl-L-ascorbic acid. For external use on the skin, which comprises 2-O-α-D-maltosyl-L-ascorbic acid-containing composition, which is 2-O-α-D-maltosyl-L-ascorbic acid (n = 2). Agent. Claimed that 90 mol% or more of the 2-O-α-D-glycosyl-L-ascorbic acid is 2-O-α-D- maltosyl -L-ascorbic acid (n = 2). Item 1. The external skin preparation according to Item 1. The proportion of 2-O-α-D-glycosyl-L-ascorbic acid having n = 4 or more in the 2-O-α-D-glycosyl-L-ascorbic acid is 1 mol% or less. The external skin preparation according to claim 1 or 2. The external skin preparation according to any one of claims 1 to 3, wherein the 2-O-α-D-maltosyl-L-ascorbic acid-containing composition is a powder. (A) The following general formula (1)

(In the formula, n indicates an integer of 1 or more.)
A step of preparing a mixture of 2-O-α-D-glycosyl-L-ascorbic acid represented by 2 and containing all of 2-O-α-D-glycosyl-L-ascorbic acid having n = 1 to 7. ,
(B) A step of allowing β-amylase to act on the mixture, and
(C) 2-O-α-, which comprises a step of purifying the mixture on which β-amylase is allowed to act to obtain a 2-O-α-D-maltosyl-L-ascorbic acid-containing composition. A method for producing a D-maltosyl-L-ascorbic acid-containing composition.