KR950000259B1 - Process for purifying 5'-sodium guanylate - Google Patents

Abstract

A solvent of methanol or ethanol is added to a solution of 5'-sodium guanylate of 8.4-8.6 pH, and concentration is 25-30 % when coming to 37-40 (v/v)% as concentration that can crystallize. After adding, a rise of concentration is stopped and again solution of guanylic acid is independently added to this. The guanosine 5'-monophosphate, disodium salt hydrate (I) is crystallized. The obtd. cpd. is useful as additives of foods.

Description

Crystallization of 5'-Sodium Guanylate

1 is a micrograph of powdered 5'-guanylate, which was concentrated and crystallized in a conventional aqueous solution,

2 is a crystal photograph of sodium 5'-guanylate produced by the conventional reverse addition,

3 is a micrograph of sodium 5'-guanylate crystallized by the addition method in the state where a conventional inorganic salt coexisted,

4 is a micrograph of the 5'- sodium guanylate crystal produced by the present invention,

5 is a graph showing the process steps in the crystallization method of sodium 5'-guanylate of the present invention.

The present invention relates to crystallization of sodium 5'-guanylate used in food additives, and more particularly, crystallization by adding an organic solvent to a predetermined level of an aqueous 5'- guanylate solution until the organic solvent concentration that can be crystallized is reached. When the addition of the organic solvent is stopped at the organic solvent concentration possible (stopping the increase in the concentration of the system), the process of adding only the 5'-sodium guanylate aqueous solution alone is repeatedly performed to obtain industrially good sodium 5'-guanylate 7H. ₂ O relates to obtaining a decision.

Sodium 5'-Guanylate is a substance that has a strong taste of shiitake mushrooms. It is 2,3 times more flavor than sodium 5'-Guanylate and has a synergistic effect when combined with sodium L-Glutamate. Availability is increasing day by day.

Sodium 5'-guanylate (hereinafter referred to as GMP 2Na) is extremely difficult to crystallize out of solution and is unlikely to be produced amorphous. Therefore, conventionally, the precipitate was dried to obtain only GMP 2Na in powder form (see FIG. 1). However, the obtained GMP 2Na is difficult to separate solid-liquid and has many limitations in quality improvement and industrial production. .

Thereafter, there has been a case of successful crystallization of a good columnar form of GMP 2Na by adding certain salts on a specific organic solvent (Japanese Patent Publication No. 52-45778). Since then, this purification method has been further developed and several methods of crystallization are known. However, these methods may include adding GMP 2Na aqueous solution to the organic solvent (reverse addition) (Figure 2), adding specific organic solvents to the GMP 2Na aqueous solution (corrective method) (Figure 3), or organic solvents and GMP. As a method of adding 2Na aqueous solution simultaneously, each method had a limited number of elements, which was inconvenient for industrial production. That is, in the case of the reverse addition, since the GMP 2Na aqueous solution having a predetermined condition is crystallized at the moment of being added to the organic solvent, fine needle-shaped crystals are produced (FIG. 2), but it takes a long time even if not. On the other hand, in the case of the positive addition, the crystallization depends on the content of impurities in the aqueous solution of GMP 2Na, and it takes a long time to decompose the target substance GMP 2Na, and in the case of simultaneous addition, compared to the reverse addition A rather good crystal was obtained, but had many disadvantages due to manufacturing complexity.

In order to solve this problem, the present inventors, after a long study, found that fixing the concentration of an organic solvent in the presence of a small amount of inorganic salts can mass produce GMP 2Na.7H ₂ O crystals (Fig. 4). The crystallization method was completed.

The present invention stops the addition of an organic solvent at a concentration capable of crystallization by adding an organic solvent until a crystallable concentration is reached in a GMP 2Na aqueous solution of a certain level (stopping the concentration increase of the system), and again only the GMP 2Na aqueous solution alone. by carrying out the step of repeatedly adding to a method for obtaining a good GMP 2Na · 7H ₂ O crystals industrially.

The present invention is greatly industrially advantageous in the following points.

1. By reducing the crystallization time and reducing the decomposition rate, the recovery rate is increased and thus the quality is improved.

2. Crystallization is possible under the influence of impurities in GMP 2Na aqueous solution.

3. Large crystal (figure 4) makes it easy to separate solid-liquid and improve quality.

4. It can do the maximum production with little space and automate the equipment.

Hereinafter, the present invention will be described in detail.

In order to crystallize by the method of the present invention, the following main conditions necessary must be met.

<end. pH condition>

Crystallization results according to the pH of the solution by the crystallization method by a specific method from GMP 2Na aqueous solution is shown in Table 1 below.

TABLE 1

* Inorganic salt quantity is constant use (Inorganic salt wt / GMP 2Na wt)

* Method of crystallization: Jeongseok

As seen in the table above, the pH at crystallization was the highest in 8.5 ± 0.1 and the cause was thought to be due to the balance of 2Na / GMP 2Na and the relationship could be explained.

In addition, by lowering the viscosity of the solution (VISCOSITY) it is thought that the faster the mass transfer rate, the faster the adsorption rate of GMP 2Na, the target substance to the crystal nucleus, the gentle crystallization proceeded.

Therefore, it is preferable that the aqueous solution of GMP 2Na used in the present invention has a pH of 8.5 ± 0.1, and when the pH is low, needle-shaped long crystals are generated, resulting in poor mother liquor separation and poor yield.

<I. Concentration of GMP 2Na Aqueous Solution>

Since the produced GMP 2Na crystal or GMP 2Na crystal added during crystallization adsorbs and grows GMP 2Na in a dissolved state, crystallization at low concentrations is not suitable for obtaining large crystals. In addition, in the case of a high concentration of solution, amorphous GMP 2Na produced by cooling, etc. is present, which makes it difficult to handle the solution. Specifically, in the case of 25% to 30% of the solution, it did not affect the crystallization according to the present invention in a completely dissolved state, and even a low concentration of the solution of 25% or less is possible to crystallize, but the amount of discharge into the mother liquor reduces the recovery rate, In the present invention, it is preferable to use 25 to 30% of GMP 2Na aqueous solution.

<All. Crystalline Temperature>

When crystallized by the crystallization method of the present invention, the GMP 2Na crystal form was changed according to temperature, and columnar crystals (GMP 2Na · 7H ₂ O) were formed at 45 ° C. or lower, but plate-shaped crystals (GMP 2 Na ·. Since 4H ₂ O) has been produced, the crystallization temperature is preferably selected to be 40 ° C. ± 5 ° C. standard.

<la. Concentration of organic solvent>

As a result of adding and observing a seed while slowly adding a specific organic solvent to the GMP 2Na aqueous solution, it was found that the crystallization proceeds only when the concentration of the organic solvent is constant. Several experiments showed that the concentration of organic solvent at the starting point of crystal formation was optimal at 37-40 v / v% when the other conditions (pH, temperature, concentration) were constant. Therefore, in the crystallization method of this invention, it is preferable to make the density | concentration of an organic solvent into 37 to 40%, and it is preferable to use alcohol, such as methanol and ethanol, as an organic solvent.

The crystallization method of the present invention is a method of crystallizing continuously by the mutual salting effect of inorganic salts and GMP 2Na in a certain concentration of an organic solvent, even if a small amount of inorganic salts is used than the amount of inorganic salts used in conventionally known methods. Crystallization is possible, so the quality of the crystal is good. In the crystallization method of the present invention, inorganic salts containing Na as an additive are used. Preferably Na ₂ HPO ₄ is used.

The crystallization method of the present invention stops the addition of the organic solvent on the organic solvent concentration that can be crystallized by adding the organic solvent to the GMP 2Na aqueous solution described above until the organic solvent concentration that can be crystallized (concentration of the system) As a method of repeatedly performing the step of adding the only GMP 2Na aqueous solution alone again to stop the rise, the principle is described with reference to FIG.

In FIG. 5, A and B are saturation curves and C and D are supersaturation curves. When organic solvent is added to GMP 2Na aqueous solution with C1 concentration, GMP 2Na is poorly soluble in organic solvent and the system gradually increases to reach S1 point on saturation curve. At this time, the concentration of the organic solvent is called O1, and if the concentration of the organic solvent is continuously increased, the saturation point S'1 is reached. Crystallization of the material which can be crystallized by cooling and evaporation crystals will proceed at any point between S1-S'2, but in the case of crystallization of GMP 2Na by organic solvents under certain conditions, an amorphous form is continuously produced.

Crystallization proceeded when the concentration of organic solvent was increased to reach O3, and the concentration of the system was lowered to reach the point S3. It was found that the amount of crystal formed was the mass of (P1-P3), and crystallization proceeded almost instantaneously at the point O3, at which time it crystallized more than 80%.

Subsequently, the organic solvent is added to the concentration of O4, and crystallization proceeds again, at which time the concentration of the mother liquor becomes P4. Small amounts of impurities contained in the aqueous solution are also coprecipitated or liberated in S3-S'3. Therefore, in the case of GMP Na, solute crystallization time (crystal growth time) is very short, so it can be seen that these causes are obstacles to the formation of large crystals. For this reason, in the present invention, only the solution is added at the point P2 (without the addition of an organic solvent) to prevent the rapid decrease of the GMP 2Na concentration to the point of rapid adsorption, that is, the concentration of the system to the point S'2. After increasing the crystallization, the concentration of the organic solvent lowered by the added solution increases the concentration to 40% linear. As a result of maintaining the crystal system stepwise, it is possible to obtain crystals of good columnar GMP 2Na.7H ₂ O, and succeed in crystallization with the least effect of impurities in the GMP 2Na aqueous solution. In this case, the inorganic salts in the solution phase do not crystallize, so crystallization is possible even with a small amount of inorganic salts. do.

Hereinafter, the present invention will be described in detail by way of examples.

Example 1

After dissolving 40% of Na ₂ HPO _{4 in} 500 ml of methanol and completely dissolving, 25 g of GMP 2Na.7H ₂ O seed was added thereto while stirring for 10 to 20 minutes in a water bath at 40 ° C. (120 REV / MIN). After completely equilibrated, 1000 ml of 30% GMP 2Na aqueous solution and methanol were repeatedly stabilized for 1.5 hours, and then dehydrated and dried to obtain 293 g of columnar crystals of GMP 2Na · 7H ₂ O. 99.8% and 90% yield. 1,000 ml of methanol was used for crystallization.

Example 2

After dissolving 40% of 12.5 g of Na ₂ HPO _{4 in} 500 ml of methanol and completely dissolving, 25 g of GMP 2Na · 7H ₂ O seed was added thereto while stirring for 10 to 20 minutes in a water bath at 40 ° C. (120 REV / MIN). After fully equilibrated, 1500 ml of 30% GMP 2Na aqueous solution and methanol were repeatedly stepwise crystallized for 2 hours, followed by dehydration and drying to obtain 419 g of columnar crystals of GMP 2Na · 7H ₂ O. 99.9% and yield 91.11%. In crystallization, 1,330 ml of methanol was used.

Example 3

After dissolving 40% of Na ₂ HPO _{4 in} 500 ml of methanol and completely dissolving, 25 g of GMP 2Na · 7H ₂ O seed was added thereto while stirring for 10-20 minutes in a water bath at 35 ° C. (120 REV / MIN). After completely equilibrated, 1000 ml of 25% GMP 2Na aqueous solution and methanol were repeatedly stepwise crystallized for 2 hours, and then dehydrated and dried to obtain 220 g of GMP 2Na · 7H ₂ O columnar crystals. 99.9% and 88% yield. 1,000 ml of methanol was used for crystallization.

Example 4

After dissolving 40% of 12.5 g of Na ₂ HPO _{4 in} 500 ml of methanol and completely dissolving, 25 g of GMP 2Na · 7H ₂ O seed was added thereto while stirring for 10 to 20 minutes in a water bath at 35 ° C. (120 REV / MIN). After fully equilibrated, 1500 ml of 25% GMP 2Na aqueous solution and methanol were repeatedly stepped for 2.0 hours, and dehydrated and dried to obtain 335 g of columnar crystals of GMP 2Na · 7H ₂ O. 99.9% and yield 89.3%. In crystallization, 1,300 ml of methanol was used.

Example 5

666ml of methanol was added to 1000ml of 30% GMP 2Na aqueous solution at 38 ° C, and crystallized. When the alcohol concentration was 40%, the system was made stepwise by repeatedly adding 1500ml of GMP 2Na 30% aqueous solution and methanol and dehydrated and dried for 1 hour. 695 g of GMP 2Na.7H ₂ O was obtained, and the crystal analysis result was 20.6% moisture and 99.8% purity. In crystallization, 1,445 ml of methanol was used, and the yield was 92.7%.

Example 6

627ml of methanol was added to 1000ml of 25% GMP 2Na aqueous solution at 38 ℃, and crystallized. When the alcohol concentration was 40%, the system was made stepwise by repeatedly adding 1500ml of GMP 2Na 25% aqueous solution and methanol. 557.8 g of GMP 2Na.7H ₂ O was obtained. The crystal result was 21.2% moisture and 99.9% purity. 1,445 ml of methanol was used for crystallization, and the yield was 88.96%.

Claims (4)

The organic solvent was added to an aqueous solution of 5'- sodium guanylate (hereinafter referred to as GMP 2Na) until the concentration of the organic solvent capable of crystallization was reached and the addition of the organic solvent was stopped at the organic solvent concentration capable of crystallization. A method for crystallizing sodium 5'-guanylate, characterized by stopping the increase in concentration and repeatedly adding only GMP 2Na aqueous solution alone. The method for crystallizing sodium 5'-guanylate according to claim 1, wherein the concentration of the organic solvent is kept constant at 37 to 40% (v / v). The crystallization method of sodium 5'-guanylate according to claim 1 or 2, wherein an aqueous solution of GMP 2Na having a pH of 8.4 to 8.6 and a concentration of 25 to 30% is used together with inorganic salts containing Na. The method of claim 1 or 2, wherein the organic solvent is alcohol such as methanol or ethanol.