KR101047833B1 - Method for preparing 5'-guanylate crystal using salt additive - Google Patents

Abstract

In the method for preparing 5'-guanylate crystals according to the present invention, a salt containing calcium is added to the mixed solution formed by adding an alcohol-based antisolvent to a 5'-guanylic acid solution to add a salt containing calcium as a additive. It is characterized by obtaining the 5'-guanylate hexahydrate. Methanol or ethanol may be used as the alcohol-based antisolvent. The alcoholic antisolvent is preferably added to the 5'-guanylic acid solution to account for 50% (V / V) of the mixed solution. As the salt containing calcium, calcium chloride (CaCl ₂ ) or calcium carbonate (CaCO ₃ ) is preferably used. It is preferable that the salt containing calcium is added to the mixed solution at 0.05 to 5% by mass. According to the present invention, since the antisolvent (methanol) is added at once without dividing the antisolvent, the antisolvent input time is greatly shortened. As a salt additive that grows the size of the guanylate crystal, a salt containing Ca is newly used instead of a salt containing Na, which is about 2 times larger than the conventional one without adding a seed. 5'-guanylate having a crystal size of 400 μm can be obtained with high purity (99.9%).

5'-guanylate, calcite crystallization, calcium chloride, calcium carbonate, methanol

Description

Method for fabricating guanosine 5'-monophosphate salt hydrate crystal using salt additive}

The present invention relates to a method for preparing 5'-guanylate crystals using salt additives, and more particularly, to a method for preparing high purity (more than 99.9%) 5'-guanylate crystals having a crystal size of 400 um.

5'-Guanylate is a white powdery solid that is widely used as seasoning for food additives with strong shiitake mushroom taste. 5'-guanylate is obtained in crystal form by drowning-out crystallization using alcoholic antisolvents (methanol, ethanol, and acetone). In particular, as shown in Korean Patent Application Nos. 1986-0000048, 1984-0007088, and 1991-0019655, when the crystallization temperature is room temperature, 5'-guanylate in the form of a heptahydrate is obtained. Form 5'-guanylate is obtained. Crystalline 5'-guanylate (7-hydrate) is produced by agolite crystallization at room temperature, and more specifically, amorphous 5'-guanylate is first formed during crystallization, and over time amorphous 5'-guanylate The salt is redissolved and acts as a driving force for nucleation and crystal growth of the crystalline form (7-hydrate), resulting in phase transformation into crystalline 5'-guanylate (7-hydrate).

However, the crystallization method specified in the patent application is divided into small amounts of anti-solvents such as methanol and ethanol in small portions, and the average crystal size of 5'- guanylate (hexahydrate) is about 200 μm, which is small, and due to uneven nucleation. The size distribution of crystals is wide, and the purity of 5'-guanylate is low.

Therefore, the technique of forming large 5'-guanylate crystals of high purity over 300um in the 5'- guanylate separation process has been considered very important, and many studies and prior arts have been reported for a long time.

Korean Patent Application No. 193-0017289 discloses a method of making large crystals of 0.149-0.35 mm by seeding 5'-guanylate (hexahydrate) crystallization, in which case from 0.1 to 0.18 mm There is a disadvantage in that the seed (seed) should be put.

In addition, Korean Patent Application No. 1991-0019655 discloses a crystallization method using Na ₂ HPO ₄ salts and seeds. Specifically, 4.4 g of Na ₂ HPO ₄ was completely dissolved in 500 ml of methanol, followed by stirring for 10-20 minutes in a water bath at 40 ° C., and 25 g of 5′-guanylate (hexahydrate) seed was added thereto. Stir as much as possible. Thereafter, 1000 ml of an aqueous 30% 5'- guanylate (7-hydrate) solution and methanol were repeatedly used and crystallized stepwise for 1.5 hours. It is then disclosed that columnar 5'-guanylate (hexahydrate) with a crystal size of about 200 um with a purity of 99.8% is obtained. However, in this case, there is a disadvantage in that it takes a lot of time according to the divided input of methanol and addition of seeds is required.

Therefore, the problem to be solved by the present invention is to simplify the input of methanol once, significantly reducing the time required by the divided input of methanol, even if the seed (seed) is not added by using a new salt additive that has not been used conventionally The present invention provides a method for preparing 5'-guanylate crystals, in which 5'-guanylate crystals (hexahydrate) having a size of 400 um can be prepared in high purity (99.9% or more).

5'- guanylate crystal production method according to the present invention for achieving the above object, to grow the size of the guanylate crystal in a mixed solution in which the alcohol-based anti-solvent is added to the 5'- guanylic acid solution of the formula (1) It is characterized by obtaining a crystalline 5'- guanylate hexahydrate by adding a salt containing calcium as an additive.

[Formula 1]

Methanol or ethanol may be used as the alcohol-based antisolvent. The alcohol-based antisolvent is added to the 5'-guanylic acid solution in one portion rather than in one portion. The alcoholic antisolvent is preferably added to the 5'-guanylic acid solution to account for 50% (V / V) of the mixed solution.

As the salt containing calcium, calcium chloride (CaCl ₂ ) or calcium carbonate (CaCO ₃ ) is preferably used. The calcium-containing salt is preferably added to the mixed solution at 0.05 to 5% by mass.

According to the present invention, since the antisolvent (methanol) is added at once without dividing the antisolvent, the antisolvent input time is greatly shortened. As a salt additive that grows the size of the guanylate crystal, a salt containing Ca is newly used instead of a salt containing Na, which is about 2 times larger than a conventional seed without adding a seed. 5'-guanylate having a crystal size of 400 μm can be obtained with high purity (99.9%). Conventionally, high-purity 5'-guanylate hexahydrate crystals of 99.9% or more could not be obtained while forming crystals having a size of 400 μm or more.

Hereinafter, with reference to the accompanying drawings, preferred embodiments of the present invention will be described in detail. The following embodiments are only presented to understand the content of the present invention, and those skilled in the art may make many modifications within the technical spirit of the present invention. Therefore, the scope of the present invention should not be construed as limited to these embodiments.

1 is a view for explaining the separation step for the molten crystallization method according to the present invention. The following embodiment will be described with reference to FIG. 1.

Example 1

At room temperature of 25 ° C., 250 ml of prepared 5'-guanylate 10% aqueous solution is prepared, and 250 ml of methanol having a purity of 99.5% is mixed in a 500 ml batch crystallizer at a rate of 50% (V / V) at a time. If amorphous forms in the entire solution, ca 0.25 g of CaCl ₂ is mixed after about 10 seconds and wait until the system is equilibrated. After crystallization, crystals of the 5'- guanylate hexahydrate columnar type were obtained, and the average crystal size at this time was 411 um. HPLC analysis showed that the purity was 99.9%.

[Example 2]

At room temperature of 25 ° C., 250 ml of prepared 5'-guanylate 12% aqueous solution is prepared, and 250 ml of methanol having a purity of 99.9% is mixed in a 500 ml batch crystallizer at a rate of 50% (V / V) at a time. If amorphous forms throughout the solution, mix 0.2 g of CaCl ₂ after about 3 seconds and wait until the system is equilibrated. After crystallization, crystals of 5'-guanylate hexahydrate columnar type were obtained, and the average crystal size was 438 um. HPLC analysis showed that the purity was 99.9%.

Example 3

At room temperature of 25 ° C., 250 ml of prepared 5'-guanylate 10% aqueous solution is prepared, and 250 ml of methanol having a purity of 99.9% is mixed in a 500 ml batch crystallizer at a rate of 50% (V / V) at a time. When amorphous forms throughout the solution, after about 1 minute, 0.05 g of CaCl ₂ is mixed and wait until the system is equilibrated. After crystallization, crystals of 5'-guanylate hexahydrate columnar type were obtained, and the average crystal size was 438 um. HPLC analysis showed that the purity was 99.9%.

2. How to measure purity and crystal size

Purity of 5′-guanylate was measured using HPLC (using a C-18 column) and crystal size was measured using a particle size analyzer and a microscope.

According to the present invention, since the methanol is added at one time without dividing the methanol, the methanol input time is greatly shortened. And calcium salts (Ca) instead of Na salts, such as Na ₂ HPO ₄ [National Patent Application No. 199-0019655] and Na ₂ HCO ₃ [National Patent Application No. 1990-0013563], which have conventionally been used as salt additives. By using a new salt additive to obtain a high purity (99.9%) of 5'-guanylate having a crystal size of 400 um, which is about 2 times larger than the conventional one without seeding (seed).

Figure 2 is a photograph showing the crystal size of the conventional 5'- guanylate prepared by the addition of Na ₂ HPO ₄ salt (x250), Figure 3 is a 5'- according to the present invention prepared by the addition of Ca ₂ CO ₃ salt This is a picture showing the crystal size of guanylate (x100). 2 and 3, the 5'-guanylate salt manufacturing method according to the present invention in which Ca salt is added is larger in crystal size than the conventional 5'-guanylate (hexahydrate) manufacturing method in which Na salt is added. You can see that it is larger.

1 is a view for explaining a separation step for the molten crystallization method according to the present invention;

Figure 2 is a photograph (x250) showing the crystal size of the conventional 5'- guanylate prepared by the addition of Na ₂ HPO ₄ salt;

Figure 3 is a photograph showing the crystal size of 5'- guanylate according to the present invention prepared by adding Ca ₂ CO ₃ salt (x100).

Claims (7)

A crystalline 5'-guanylate hexahydrate is obtained by adding a salt containing calcium as an additive for growing the size of guanylate crystals to a mixed solution in which an alcoholic antisolvent is added to a 5'-guanylic acid solution. 5'- guanylate crystal preparation method. The method for preparing 5'-guanylate crystals according to claim 1, wherein the alcoholic antisolvent is methanol or ethanol. The method of claim 1, wherein the mixed solution is added to the alcohol-based anti-solvent by adding the alcohol antisolvent to the 5'-guanylic acid solution in a single input. The method of claim 1, wherein the alcoholic antisolvent is added to the 5'-guanylic acid solution to account for 50% (V / V) of the mixed solution. The method of claim 1, wherein the salt containing calcium is calcium chloride (CaCl ₂ ) or calcium carbonate (CaCO ₃ ). The method of claim 1, wherein the calcium-containing salt is added to the mixed solution at 0.05 to 5% by mass. The method of claim 1, wherein the crystalline 5′-guanylate hexahydrate has a crystal size of 400 μm to 500 μm and has a purity of 99.9 to 99.99%.

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