JPH0350758B2 - - Google Patents

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 disadvantages 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 systems 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 found. Therefore, side reactions probably occur during the process of producing ascorbic acid phosphate magnesium salt, which is synthesized using ascorbic acid as a starting material.
It is thought that this is the reason why a small amount of impurities are mixed. As a result of intensive research, the present inventor has conducted extensive research in order to remove such impurities and obtain a purified phosphorylated ascorbic acid compound without coloration in a high yield and economically.
At last, the objective of the present invention was completed. That is, the present invention relates to a method for purifying phosphorylated ascorbic acid or its salts, which is characterized in that phosphorylated ascorbic acid or its salts are dissolved in water, and a method for purifying phosphorylated ascorbic acid or its salts is carried out using activated carbon, diatomaceous earth, acid clay, etc. The resulting liquid is adsorbed onto one or more types of carriers and decolorized, and the resulting liquid is added with one or more organic solvents selected from lower alcohols, ketones, tetrahydrofuran, etc. to form the product. The method is characterized in that it is precipitated, filtered, washed with the organic solvent, and dried. Next, the novel purification method according to the present invention will be explained in detail using ascorbic acid phosphate magnesium salt as an example.
(wt%), and a carrier such as activated carbon, diatomaceous earth, or acid clay is preferably adsorbed onto activated carbon (by elution with water) using a column method or a batch method, and then decolorized (by elution with water) to remove trace amounts of colored substances and Remove impurities. At this time, in order to remove carrier fine powder if necessary, use a Milpore filter (Millepore Co., Ltd.).
etc. to perform overprocessing. One or more types selected from lower alcohols such as methanol, ethanol, isopropanol, butanol, isobutanol, ketones such as acetone, tetrahydrofuran, etc. organic solvent 20-55
% (volume %) at room temperature for more than 10 hours, at 40°C for more than 1 hour, or at 5°C for more than 4 hours.
Leave to stand for more than an hour to precipitate ascorbic acid phosphate magnesium salt. Let this pass,
Washing with at least one of the above organic solvents, preferably methanol, ethanol, acetone, etc.,
Next, it is dried and dehydrated by an appropriate method to obtain purified magnesium salt of ascorbic acid phosphate ester in the form of a white powder. The same method was used for phosphorylated ascorbic acid peroxides 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 above purification process is maintained in the range of 20 to 55% by volume, preferably 30 to 45% by volume.
If it exceeds 55% by weight, 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% by volume, the yield will drop significantly and it will not be practical as an industrial product. The concentration of these organic solvents may be increased or decreased depending on the type of phosphorylated ascorbic acid compound targeted. What is further required is that the weight ratio of phosphorylated ascorbic acid and activated carbon carrier (adsorbent) is in the range of 1:5 to 1:0.1 (preferably 1:1 to 1).
0.2). When the amount of carrier is more than 1:5, the recovery rate decreases significantly, and when the amount of carrier is less than 1:0.1, 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 g of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) is dissolved in 500 ml of purified water. 10.0 g of activated carbon powder was added to this solution, stirred at room temperature for 30 minutes, and left to stand for 3 hours to be adsorbed onto the activated carbon and decolorized. Filter by suction, wash twice with 100 ml each of purified water, and combine the liquid and washing liquid.
This solution is filtered using a 0.22 micron Millipore filter. Add 550 ml of methanol to the solution while stirring, and leave it at room temperature overnight. The resulting white precipitate of L-ascorbic acid-2-phosphate magnesium salt is filtered, washed with acetone, and dehydrated.
Next, 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%) Example 2 20.0 g of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) is dissolved in 500 ml of purified water. Add 10.0g of diatomaceous earth (Wako) to this solution.
and 10.0 g of activated carbon powder, and stirred at room temperature for 30 minutes. The solution was left for 1 hour to be adsorbed onto diatomaceous earth and activated carbon, decolorized, and then filtered with suction. Purified water 100
Wash twice with ml each. The solution and washing solution are combined and the solution is filtered through a 0.22 micron Millipore filter over the carrier on paper. 400ml of acetone in the liquid
After adding with stirring, keep at 40℃ for 1 hour,
Heat the precipitate. After passing through this, the mixture was washed with acetone, dehydrated, and dried under reduced pressure to obtain 16.0 g of the desired white purified product. (Yield: 80.0%) Example 3 20.0 g of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) is dissolved in 400 ml of purified water. This is injected into an activated carbon column (10.0 g of activated carbon for Wako chromatography dispersed in water and packed into a glass column with a diameter of 5 cm) and allowed to pass through, where it is adsorbed onto the activated carbon and decolorized. Elute with purified water, and end the elution when the total volume of the column-passing liquid reaches 1000 ml. Filter the column flow through a 0.22 micron Millipore filter to remove activated carbon particles. Add ethanol while stirring the liquid.
Add 600ml and leave it overnight to dissolve L-ascorbic acid.
2-Phosphate ester magnesium salt is precipitated. After passing through this, the residue was washed with ethanol (first grade) and dried under reduced pressure to obtain 14.7 g of the desired purified product. (Yield 73.5%) Example 4 30.0 g of L-ascorbic acid-2-phosphate magnesium salt (unpurified product) is dissolved in 500 ml of purified water. This is injected into an activated carbon column (20 g of activated carbon for Wako chromatography dispersed in water and packed into a glass column with an inner diameter of 5 cm) and allowed to pass through, where it is adsorbed onto the activated carbon and decolorized. Elute with purified water, and end the elution when the total volume of the column-passing liquid reaches 1000 ml. Filter the column flow through a 0.22 micron Millipore filter to remove activated carbon particles. While stirring the solution, 650 ml of primary acetone was added, and the mixture was allowed to stand at 5°C for 4 hours to precipitate the magnesium salt of primary acetone L-ascorbic acid-2-phosphate. Next, the mixture was filtered, washed with acetone, and dried under a nitrogen stream while stirring to obtain 23.8 g of the desired purified product. (Yield 79.3%) 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 3 parts per 100 parts of an aqueous solution of 0.1 to 5% (wt%) phosphorylated ascorbic acid compound. The results of stability tests of aqueous solutions of the purified phosphorylated ascorbic acid compound and the unpurified phosphorylated ascorbic acid compound of the present invention are shown in Table 1 (high temperature stability) and Table 2 (temporal stability) below. gender). In addition, the samples in Tables 1 and 2 were pH-treated with NaOH (1-N) and HCl (1-N).
It has been adjusted 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 phosphate ester magnesium salt content (residual rate %): The content of ascorbic acid phosphate ester magnesium salt is measured by the iron salt colorimetric method, and is a unified value when the time of sample preparation (untreated) is set as 100. Shown as value (%).

[Table] The unrefined product was considerably colored from the beginning, but the treatment at 100°C resulted in severe coloration and a foul odor. On the other hand, the purified product showed only a slight amount of coloring and did not develop any odor even after being treated at 100°C for 3 hours. Although the addition of citric acid has a considerable effect on purified and unrefined products, it alone was not able 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.

[Table] 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 3 shows the influence of solvent concentration, etc. during purification of the phosphorylated ascorbic acid compound.

[Table] The lower the ethanol concentration, the higher the purification effect. In general, solvent concentrations below 55% (volume %) were effective for purification. In other experiments, similar effects were observed with lower alcohols such as methanol and isopropanol, and ketones such as acetone. However, if the solvent concentration is less than 20% (volume %), the recovery rate will be low and it is not industrially practical. Specifically, the phosphorylated ascorbic acid compounds purified by the present invention include L-ascorbic acid-3-phosphate, L-ascorbic acid-2
-Phosphate ester magnesium salt, same calcium salt, same sodium salt, L-ascorbic acid pyrophosphate 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, and provides various stable phosphorylated ascorbic acid compounds without coloration in good yield and 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.

Claims (1)

[Claims] 1 Dissolve phosphorylated ascorbic acid or its salts in water and decolorize it by adsorbing it on at least one type of carrier selected from activated carbon, diatomaceous earth, acid clay, etc., and lower alcohols, At least one organic solvent selected from ketones, tetrahydrofuran, etc.
A method for purifying phosphorylated ascorbic acid or its salts, which comprises adding the product to a concentration of 20 to 55% by volume to precipitate the product, filtering it, washing it with the organic solvent, and drying it. .