JPS59106494A - Purification of phosphorylated ascorbic acid - Google Patents

Abstract

PURPOSE:Phosphorylated ascorbic acid or its salt is dissolved in water and treated with a carrier such as activated carbon to effect decoloration and a lower alcohol is added to the filtrate, then the precipitate is filtered off and dried to produce the titled compound used as a drug without coloration in high yield inexpensively. CONSTITUTION:After phosphorylated ascorbic acid or its salt such as magnesium 2-phosphorylated L-ascorbate is dissolved in water, at least one of carriers such as activated carbon, kiezelghur, acidic clay is used to effect adsorption treatment for decoloration, then filtered and the filtrate is combined with an organic solvent such as a lower alcohol such as methanol or a ketone. Then the precipitate formed is separated by filtration, rinsed with the organic solvent and dried to give the objective purified compound.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for purifying phosphorylated ascorbic acid or its salts.

Conventionally, ascorbic acid has been used in pharmaceuticals, foods, cosmetics, and various other industrial fields due to its excellent physiological effects. It has drawbacks such as easy coloring.

Various derivatives have been synthesized for the purpose of improving this. Among these, phosphorylated esters of ascorbic acid and their salts have the characteristic of being easily converted into ascorbic acid in vivo, and are more stable in wet products containing water than other derivatives currently available. It is said that it is also excellent.

However, even with these phosphorylated ascorbic acid compounds, for example, in the case of industrial products using ascorbic acid phosphate ester magnesium salt, in a system where water is present,
Coloration tends to progress gradually over time. Even when the ascorbic acid phosphate ester magnesium salt itself is analyzed or quantified, no decrease in its content is observed. Therefore, it is considered that a side reaction occurs during the process of producing ascorbic acid phosphate magnesium salt synthesized using ascorbic acid as a starting material, and as a result of this, trace amounts of inert substances are mixed.

The present inventor has conducted intensive research in order to remove such impurities and obtain a purified phosphorylated ascorbic acid compound without coloring in a high yield and economically, and as a result, has finally completed the objective of the present invention. That's what happened.

That is, the present invention relates to a method for purifying phosphorylated ascorbic acid or its salts, and its characteristics are as follows:
Phosphorized ascorbic acid or its salts are dissolved in water and decolorized by adsorption onto one or more carriers selected from activated carbon, diatomaceous earth, acid clay, etc., and lower alcohols or Adding one or more organic solvents of ketones to precipitate the product, allowing the product to settle, and then washing with the organic solvent,
It is characterized by drying.

Next, the novel purification method according to the present invention will be explained in detail using ascorbic acid phosphate magnesium salt as an example. Crude ascorbic acid phosphate magnesium salt is dissolved in water and 0.1 to 10 g (by weight) is dissolved in water. Then, a column method or a patch method is used to adsorb it on a carrier such as activated carbon, diatomaceous earth, acid clay, etc., preferably activated carbon, and perform a decolorization treatment (by elution with water) to remove trace amounts of colored substances and impurities. In order to remove the fine carrier powder, if necessary, filtration treatment is performed using a Milboa filter (Milboa Corporation) or the like. A type of alcohol selected from lower alcohols such as methanol, ethanol, impropatol, butanol, and imbutanol, and ketones such as acetone and nato-2-hydrofuran is applied to the obtained column-filtered liquid or patch-treated filtrate. Or two or more organic solvents for 20~
The ascorbic acid phosphate magnesium salt is precipitated by adding it to a concentration of 55% (by volume) and leaving it at room temperature for 10 hours or more, at 40°C for 1 hour or more, or at 5°C for 4 hours or more. This is filtered, washed with at least one of the above organic solvents, preferably methanol, ethanol, acetone, etc., and then dried and dehydrated by an appropriate method to obtain purified ascorbic acid phosphate magnesium salt in the form of a white powder. get.

The same method was used for phosphorylated ascorbic acid compounds other than those mentioned above, but the desired purified products were obtained.

What is important in the present invention is that the concentration of the organic solvent in the purification process is 20-55% by volume, preferably 30-4%.
This can be achieved by maintaining the capacity within the range of 5. If the volume exceeds 55 cm, impurities will precipitate together with the ascorbic acid phosphate magnesium salt, making it difficult to obtain the desired purification effect. If it is less than 20 volumes, the yield will drop significantly and it will not be practical as an industrial product. The concentrations of these organic solvents are
The amount may be increased or decreased depending on the type of phosphorylated ascorbic acid compound targeted.

Furthermore, it is necessary that the weight ratio of phosphorylated ascorbic acid and carrier (adsorbent) such as activated carbon be in the range of 1:5 to 1:0.1 (
Preferably, the ratio is 1:1 to 1:0.2). When the amount of carrier is more than 1:5, the recovery rate decreases significantly,
If the ratio of 1:0.1 carrier is small, it is difficult to obtain a purification effect.

Next, examples of the purification method of the present invention will be shown.

Example 1 10.0.9 of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) is dissolved in 500 of purified water. Add 10.0% of activated carbon powder to this solution. ! i' was added, stirred at room temperature for 30 minutes, and left to stand for 6 hours to be adsorbed onto activated carbon and decolorized. Filtered by suction filtration and purified water 100ml
Wash twice and combine the filtrate and washing liquid. Add this liquid to 0.
Filter using a 22 micron Millipore filter.

Add 5501 nl of methanol to the filtrate with stirring, and leave it at room temperature overnight. The resulting L-ascorbic acid-2,-
The white precipitate of magnesium phosphate ester salt is filtered, washed with acetone and dehydrated. Then, it was air-dried and left in a silica gel desiccator for one week to obtain 7.5 g of the desired purified product. (Yield: 75 cm) Example 2 L-ascorbic acid-2-phosphate ester magnesium salt (unrefined product) 20. Dissolve [[' in 500 ml of purified water. Add 1[1,0 g of diatomaceous earth (Wako) and 10.0 g of activated carbon powder to this solution and stir for 6 D minutes at room temperature. The mixture was left for 1 hour to be adsorbed onto diatomaceous earth and activated carbon, decolorized, and then filtered with suction. 100 d of purified water on the carrier on the paper
Wash twice. The P solution and the washing solution are combined and filtered using a 122 micron Millipore filter. After adding 400 tnl of acetone to the F solution with stirring, the mixture is kept at 40°C for 1 hour to ripen the precipitate. This was filtered, washed with acetone, dehydrated, and dried under reduced pressure to obtain 16.0 g of the desired white purified product.

(Yield: 80.0) Example 6 L-ascorbic acid-2-! Magnesium chloride ester salt (unrefined product) 20. Dissolve Cl in 400 ml of purified water. Add this to an activated carbon column (activated carbon 50 for Wako chromatography).
10.0 g of mesh was dispersed in water, poured into a glass column (filled with a diameter of 5α), allowed to pass through, and adsorbed onto activated carbon for decolorization treatment. The column is eluted with purified water, and the elution is terminated when the total volume of the column-passing liquid reaches 1000. 0.2
The column passing liquid is filtered using a 2 micron Millipore filter to remove activated carbon particles. While stirring the lachrymal fluid, 600% of ethanol was added and allowed to stand overnight to precipitate L-ascorbic acid-2-phosphate magnesium salt. Then, after filtering it, ethanol (1
The desired purified product 14 is obtained by washing and drying under reduced pressure.
．． 7g was obtained. (Yield: 76.5%) Example 4 30.0 g of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) was dissolved in 500 g of purified water. This is injected into an activated carbon column (20 g of 50 mesh of activated carbon for Wako chromatography is dispersed in water and packed into a glass column with an inner diameter of 5 crIL), allowed to pass through, and adsorbed onto the activated carbon for decolorization. The column is eluted with purified water, and the elution is terminated when the total volume of the column-passing liquid reaches 1000. 0.2
The column passing liquid is filtered using a 2 micron Millipore filter to remove activated carbon particles. While stirring the furnace liquid, 650 yd of grade 51 acetone was added, and the mixture was left at 5° C. for 4 hours to precipitate L-ascorbic acid-2-phosphate magnesium salt. Next, this is filtered, washed with acetone, stirred and dried under a nitrogen stream to obtain the desired purified product 2.
3.8, li' was obtained. (Yield: 793 cm) By adding the purified phosphorylated ascorbic acid or its salts obtained as described above to various aqueous solutions, an aqueous solution containing a stable phosphorylated ascorbic acid compound without coloration is provided. It is. In order to further improve stability, one or two organic acids such as citric acid, tartaric acid, and malic acid may be added. The appropriate amount of such an organic acid is 0.1 to 6 parts per 100 parts of an aqueous solution of 0.1 to 5% (weight %) of the phosphorylated ascorbic acid compound.

The results of a stability test of aqueous solutions of the purified phosphorylated ascorbic acid compound of the present invention and the unpurified phosphorylated ascorbic acid compound are shown in Table 1 (high temperature stability) and Table 2 (temporal stability). gender). Furthermore, the table-
The samples in Table 1 and Table 2 are Na0H (1-N) and HC.
'! (1-N) to adjust the pH to 8.0.

Measurement of coloration: The degree of coloration was measured by the absorbance of the sample at 360 nm (cell length 1 cm).

Data were expressed as absorbance.

Ascorbic acid sulfate ester magnesium salt content (
Residual rate (%): The content of ascorbic acid phosphate magnesium salt was measured by the iron salt colorimetric method.
Relative value (shown as (6)) when non-treated) is set as 100.

(Shisumi #, coloring unrefined coloring is recognized from the beginning, but it is 100%
Due to the treatment at ℃, it was intensely colored and had a bad odor. On the other hand, refined products have only a small amount of wear.
No odor was observed even after treatment at -6 hours.

Although the addition of citric acid was found to be effective in reducing odor and coloration in purified and unrefined products, this alone was not sufficient to prevent odor and coloration. In another experiment, it was found that organic acids such as tartaric acid and malic acid had the same effect as citric acid.

Even in the aging test at 40°C and room temperature, the purified product was hardly or only slightly colored, and a remarkable purification effect was observed.

However, the ascorbic acid phosphate magnesium salt content hardly changed, and it is presumed that the cause of the coloring was a small amount of coexisting impurities.

Furthermore, Table 6 shows the influence of solvent concentration, etc. during purification of the phosphorylated ascorbic acid compound.

The lower the ethanol concentration, the higher the fif production effect. In general, solvent concentrations of 55% (vol%) or less were effective for purification. In other experiments, similar effects were found with methanol, lower alcohols such as Improper Tools, and ketones such as acetone. However, the solvent concentration is 20 yen (volume%)
) is not industrially practical due to the low recovery rate.

Specifically, the phosphorylated ascorbic acid compounds purified by the present invention include L-ascorbic acid-3-1t ester, L-ascorbic acid-2-phosphoric ester magnesium salt, calcium salt, and sodium salt. ,L-
These include ascorbic acid birophosphate magnesium salt and various other compounds.

As detailed above, the present invention relates to a novel method for purifying phosphorylated ascorbic acid or its salts, which produces various stable phosphorylated ascorbic acid compounds without coloration in good yields.
Supplied in high purity. The purified phosphorylated ascorbic acid compound obtained by the present invention is applied to various industrial fields, and in particular, in cosmetics, it is useful not only for producing color-free products in aqueous solutions such as lotions, but also for creams, milky lotions, etc. ,
The present invention provides an ascorbic acid compound that can be used in gels, powders, etc., and has unprecedented quality characteristics and physiological activity.

Patent applicant: POLA CHEMICAL INDUSTRIES, INC.

Claims (1)

[Claims] 1. Dissolve phosphorylated ascorbic acid or its salts in water and adsorb it on one or more carriers selected from activated carbon, diatomaceous earth, acid clay, etc. for decolorization, and add lower alcohol to the resulting tear fluid. Phosphated ascorbin, characterized in that the product is precipitated by adding one or more organic solvents of the above-mentioned or ketones, and the product is filtered, washed with the organic solvent, and dried. Method for purifying acids or their salts.