METHOD FOR PREPARING DISODIUM 5'-GUANYLATE HEPTAHYDRATE CRYSTAL

Abstract

A method is provided for preparing disodium 5'-guanylate heptahydrate crystals from an aqueous solution of 5'-guanylic acid.

Description

METHOD FOR PREPARING DISODIUM 5'-GUANYLATE HEPTAHYDRATE CRYSTAL Field of Invention This description relates to a method for preparing disodium 5'-guanylate heptahydrate crystals. In particular, this description relates to a method for obtaining disodium 5'-guanylate heptahydrate crystals by concentration crystallization without the use of an organic solvent. Background of the Invention Disodium 5'-guanylate crystals are generally known to exist in an amorphous form, a plate-like tetrahydrate form, and a pillar-like heptahydrate form. Since the amorphous crystals are difficult to separate, transport, and store using solid-liquid separation methods, the heptahydrate form is primarily used in industry. One method for industrially obtaining the crystals employs a hydrophilic organic solvent such as methanol, ethanol, etc., which is an alcohol-based antisolvent. The crystallization method using an organic solvent leads to crystals that have a residual hydrophilic organic solvent in them. Qezfrnn / zznz / E / YiAi Ref. 332744 after drying, which makes users anxious. In addition, it is necessary to obtain the organic solvent with high purity in a process to recover the hydrophilic organic solvent used in the process, which requires high costs including investment in a distillation column and related utility costs, and generates costs for explosive environments for worker safety. Accordingly, the present inventors have conducted experiments to improve the above method and have discovered that disodium 5'guanylate heptahydrate crystals can be obtained without using an organic solvent, thus completing the present description. Summary of the Invention TECHNICAL PROBLEM One aspect provides a method for preparing disodium 5'-guanylate heptahydrate crystals, the method includes mixing an aqueous saline solution and an aqueous solution of 5'-guanylic acid to form amorphous solids in a mixed solution; and adding seed crystals to the mixed solution to form disodium 5'-guanylate heptahydrate crystals, wherein the addition of the seed crystals is carried out while maintaining the temperature from 25°C to 45°C. Qezfrnn / zznz / E / YiAi SOLUTION TO THE PROBLEM One aspect provides a method for preparing disodium 5'-guanylate heptahydrate crystals, the method includes mixing an aqueous saline solution and an aqueous solution of 5'-guanylic acid to form amorphous solids in a mixed solution; and adding seed crystals to the mixed solution to form disodium 5'-guanylate heptahydrate crystals, wherein the addition of the seed crystals is carried out while maintaining the temperature from 25°C to 45°C. In this method, the aqueous saline solution can be at a pH of 7 to 10. The addition can be made while the temperature of the mixed solution is maintained from 25°C to 45°C. The aqueous saline solution can have any salt concentration so that it mixes with the aqueous 5'-guanylic acid solution to form the mixed solution having a salt concentration of 160 g / L to 360 g / L. For example, the aqueous saline solution can be an aqueous saline solution of 200 g / L to 400 g / L. An aqueous solution of 5'-guanylic acid can be prepared by adding 5'-guanylic acid to water. The aqueous solution of 5'-guanylic acid can range in concentration from 50 g / L to 400 g / L. The aqueous solution of 5'-guanylic acid may include a salt. For example, it could be an aqueous solution of disodium 5'-guanylate. The aqueous solution of 5'-guanylic acid may include those obtained by means of a microbial culture. Those obtained by means of a microbial culture may be a supernatant obtained by removing cells from a microbial culture containing 5'-guanylic acid. Those obtained by means of a microbial culture may be those obtained by purifying the supernatant using ion-exchange chromatography or activated carbon. Purification using activated carbon may involve mixing activated carbon and the culture to allow impurities to bind to the activated carbon and removing the activated carbon to which the impurities bind from the mixture. In this method, the aqueous 5'-guanylic acid solution is mixed until the salt concentration in the mixed solution increases from 160 g / L to 360 g / L. The NaCl concentration in the mixed solution also increases from 160 g / L to 360 g / L. In this method, the formation of amorphous solids may involve drying the mixed solution to increase the salt concentration from 160 g / L to 360 g / L. Mixing the aqueous 5'-guanylic acid solution may involve adding the solution in portions. The addition may be dropwise. The addition may be carried out over a period of 1 minute to 1000 minutes. The mixing of the aqueous 5'-guanylic acid solution may be performed under stirring. As used in this document, the term amorphous solid refers to a white solid that does not have any crystalline form like a crystal, but precipitates randomly. Amorphous solids float in a solution and have a non-transparent, irregular, and opaque shape because they are amorphous. When this amorphous solid dries, it can be identified as an anhydride in hydrate analysis. In this method, the addition of seed crystals can be performed while maintaining the temperature of the mixed solution between 25°C and 45°C. The seed crystals may include disodium 5'-guanylate heptahydrate crystals. The addition of the seed crystals can be performed while stirring a reactor. The addition of the seed crystals can be done in portions or dropwise. The addition can be carried out over a period of 1 minute to 1000 minutes. The amount of seed crystals added can be based on the weight of 5'-guanylate in the mixed solution of aqueous 5'-guanylic acid and the solution. Qezfrnn / zznz / E / YiAi aqueous saline. The amount of seed crystals added can be from 0.1 parts by weight to 5.5 parts by weight or from 0.1 parts by weight to 5.0 parts by weight, based on 100 parts by weight of 5'-guanylate. The 5'-guanylate can be, for example, disodium 5'-guanylate. The method may also include cooling the solution containing the crystals formed after the disodium 5'-guanylate heptahydrate crystals have formed. Cooling can be carried out at 25°C or lower, for example, from 4°C to 25°C, 4°C to 20°C, 4°C to 15°C, 4°C to 10°C, 10°C to 25°C, 15°C to 25°C, or 10°C to 20°C. The method may also include separating the crystals from the solution, including the crystals formed after the disodium 5'-guanylate heptahydrate crystals have formed. Separation can be performed by centrifugation or filtration. Centrifugation can be carried out at 100 g to 1000 g for 1 to 30 minutes. Filtration can be performed using a 0.22 µm to 200 µm filter. In this method, the aqueous saline solution can be an aqueous solution of a metal salt. In other words, the salt in the aqueous saline solution can be a metal salt. The metal salt can include an alkali metal salt. The alkali metal salt can be a salt containing sodium. The alkali metal salt can be NaCl, Qezfrnn / zznz / E / YiAi KC1, Na2CO3, NaHCO3 or Na2CO3. One embodiment provides a method for preparing disodium 5'-guanylate heptahydrate crystals. The method involves forming amorphous solids in a mixed solution by blending an aqueous saline solution and an aqueous 5'-guanylic acid solution such that the salt concentration in the mixed solution ranges from 160 g / L to 360 g / L. The method further involves forming disodium 5'-guanylate heptahydrate crystals by adding seed crystals to the mixed solution, where the temperature of the mixed solution can range from 25°C to 45°C. The aqueous saline solution can be an aqueous saline solution of 200 g / L to 400 g / L. The aqueous 5'-guanylic acid solution can be an aqueous 5'-guanylic acid solution of 50 g / L to 400 g / L. The aqueous saline solution can be at a pH of 7 to 10. The seed crystals can be disodium 5'-guanylate heptahydrate crystals. The aqueous 5'-guanylic acid solution can include those obtained by microbial culture.The aqueous solution of 5'-guanylic acid may include a culture obtained from a microbial culture, a culture supernatant obtained by removing cells from the culture, or purified 5'-guanylic acid from the culture. The microbe may be capable of producing 5'-guanylic acid. The amount of seed crystals added may be from 0.1 parts by weight to 5.5 parts by weight. Qezfrnn / zznz / E / YiAi based on 100 parts by weight of the 5'-guanylate formed in the mixed solution. The salt may be NaCl. The 5'-guanylate may be, for example, disodium 5'-guanylate. One embodiment provides a method for preparing disodium 5'-guanylate heptahydrate crystals. The method includes forming amorphous solids in a mixed solution prepared by mixing an aqueous solution of NaCl and an aqueous solution of 5'-guanylic acid such that the salt concentration in the mixed solution becomes from 160 g / L to 360 g / L. The method further involves forming disodium 5'-guanylate heptahydrate crystals by adding, to the mixed solution, disodium 5'-guanylate heptahydrate crystals as seed crystals in an amount of 0.1 to 5.5 parts by weight based on 100 parts by weight of 5'-guanylate formed in the mixed solution. The temperature of the mixed solution can be from 25°C to 45°C. The aqueous saline solution can be an aqueous saline solution of 200 g / L to 400 g / L. The aqueous solution of 5'-guanylic acid can be an aqueous solution of 50 g / L to 400 g / L. The aqueous saline solution can be at a pH of 7 to 10.Aqueous 5'-guanylic acid solutions may include those obtained by means of a microbial culture. Qezfrnn / zznz / E / YiAi microbial culture or a culture supernatant obtained by removing cells from the same, or purified 5'-guanylic acid from the same. The microbe may be capable of producing 5'-guanylic acid. The amount of seed crystals added may be from 0.1 parts by weight to 5.5 parts by weight, based on 100 parts by weight of 5'-guanylate. ADVANTAGEOUS EFFECTS OF THE DESCRIPTION According to a method for preparing disodium 5'-guanylate heptahydrate crystals from an aqueous solution of 5'-guanylic acid according to one aspect of the present description, disodium 5'-guanylate heptahydrate crystals can be efficiently prepared from aqueous solution of 5'-guanylic acid. Specifically, according to the method for preparing disodium 5'-guanylate heptahydrate described herein, disodium 5'-guanylate heptahydrate crystals can be obtained without adding an organic solvent. This preparation method is advantageous in terms of worker safety concerns that may arise from the use of organic solvents, as the final products do not contain any residual organic solvents, thus addressing end-user concerns about organic solvent toxicity. Furthermore, the method is Qezfrnn / zznz / E / YiAi economical because the investment for explosion-proof equipment and the costs for equipment maintenance or the investment for a distillation column and related utility costs to recover used organic solvents with high purity and the cost of utilities used for the operation of the process can be reduced. Brief Description of the Figures FIGURE 1 shows an image of disodium 5'-guanylate heptahydrate crystals obtained according to Example 1, as photographed by a microscope; FIGURE 2 shows an image of plate-like disodium 5'-guanylate tetrahydrate crystals obtained according to Comparative Example 2, as photographed by a microscope; and FIGURE 3 shows an image of disodium 5'-guanylate heptahydrate crystals obtained by means of the use of methanol which is a hydrophilic organic solvent according to Comparative Example 3, as photographed by a microscope. Detailed Description of the Invention Hereafter, this description will be explained in more detail with reference to the Examples. However, the Examples are only to illustrate this description and the scope of this description should not be limited to them. Example 1 In the Example, disodium 5'guanylate heptahydrate crystals were formed from an aqueous solution of disodium 5'-guanylate without using an organic solvent and were isolated. 0.875 L of an aqueous solution of 380 g / L disodium 5'-guanylate was slowly added to 1 L of an aqueous solution of 300 g / L sodium chloride at pH 9 and 40°C in a 3 L flask for 30 minutes. As a result, amorphous solids formed in the mixed solution. The disodium 5'-guanylate was obtained by purifying a fermentation product containing 5'-guanylic acid, which was obtained through the inventor's own microbial fermentation. The pH of the 300 g / L sodium chloride solution was adjusted by adding 2 mL of 50% (w / w) NaOH. The amorphous solids were converted to disodium 5'-guanylate heptahydrate crystals in the mixed solution at a sodium chloride concentration of 160 g / L. While the temperature of the mixed solution of aqueous sodium chloride solution and aqueous disodium 5'-guanylate solution was maintained at 42°C, the crystals of disodium 5'-guanylate heptahydrate as Seed crystals were added to the solution at a concentration of 1% by weight based on the weight of disodium 5'-guanylate formed in the mixed solution, followed by incubation under the same conditions. Within 1 hour of incubation, the amorphous solids converted to disodium 5'-guanylate heptahydrate in pillar form. As a result, the mixed solution was in the form of a thick suspension containing crystals. The term thick suspension refers to a viscous suspension in which solid-phase crystals and a liquid are mixed. The mixed solution containing crystals is hereafter also referred to as a thick crystal suspension. This shows that disodium 5'-guanylate heptahydrate in pillar form can be formed by incubating a mixed solution of aqueous sodium chloride and aqueous 5'-guanylic acid in the presence of disodium 5'-guanylate heptahydrate as seed crystals. This demonstrates that disodium 5'-guanylate heptahydrate in pillar form can be formed by incubating the mixed solution without the use of an organic solvent. This is a remarkable effect that would not have been expected by someone skilled in the field. Immediately, after 1 hour of incubation, the temperature of the thick crystal suspension cooled down. Qezfrnn / zznz / E / YiAi naturally at 25°C or less for two hours. This thick crystal suspension was placed in an H-110FMR basket centrifuge (KOKUSAN Co. Ltd., Japan) and centrifuged at a bowl G-force of 340 x g for 20 minutes. Immediately after centrifugation, the supernatant was removed to obtain a thick crystal suspension. 285 g of disodium 5'-guanylate heptahydrate crystals were obtained from the resulting thick crystal suspension. The H-110FMR centrifuge has a perforated basket installed and connected to an external rotation power supply. The perforated basket is made of a polyamide multifilament fiber filter fabric, and the filter's air permeability is 250 L / m² / sa at 2 mbar. The filtered crystals were dried at room temperature for 24 hours. The purity and concentration of the separated disodium 5'-guanylate heptahydrate crystals were analyzed using HPLC. Specifically, 1.0 g of the dry disodium 5'-guanylate heptahydrate crystal and the disodium 5'-guanylate heptahydrate standard crystal (Sigma, >99.0% (w / w) (HPLC)) were dissolved in 1 L of tertiary distilled water to prepare 1.0 g / L of the sample solution and 1.0 g / L of the standard solution, respectively. The purity of the disodium 5'-guanylate heptahydrate in the standard solution was confirmed using the certificate of the Qezfrnn / zznz / E / YiAi manufacturer of the standard reagent. Then, the concentration of disodium 5'-guanylate in the standard product was calculated by means of 1.0000 g / L x [purity of the standard product]. µL of the sample solution and the standard solution were loaded onto a column in an Agilent 1260 InfinityMR Quaternary LC system (Agilent Technology Inc.). The column was a Shiseido CAPCELL PAK C18 ACRMR (150 mm x 4.6 mm, 3 µm). Then, while applying a 2% (v / v) acetonitrile / 98% (v / v) phosphate buffer (pH 2.4) to the column at a flow rate of 1 mL / min, the absorbance at 254 nm was measured for an eluate flow rate. The phosphate buffer consisted of 2 g / L ammonium phosphate, 0.2 g / L tetrabutylammonium phosphate, and 0.82 g / L phosphoric acid. The temperature at this time was 35°C. These HPLC conditions were also used to measure the concentration of 5'-GMP in the filtrate. As a result, the purity was calculated according to the following formula. Purity = Amount of 5'-GMP / Total weight of solids x 100 In addition, 5 uL of the sample solution and the standard solution were placed respectively in a rectangular cell of a CARY 100 UV-VISMR instrument (Agilent Technology Inc.) and the transmittance was measured at 420 nm. Consequently, dried crystals of disodium 5'-guanylate heptahydrate were obtained by drying The resulting thick crystal suspension was naturally dried at 25°C for 12 hours. The dried crystals had a residual moisture content of 23.6% (w / v). The dried crystals obtained from disodium 5'-guanylate heptahydrate had a weight of 261 g, a yield of 78.0%, and a purity of 95.0%. As specified for the 5% (w / v) aqueous crystal solution, the % transmittance (T) was 95.0%, and the pH was 7.0 to 8.5. Figure 1 shows an image of the disodium 5'-guanylate heptahydrate crystals obtained according to Example 1, as photographed by a microscope. In Figure 1, the disodium 5'-guanylate crystals are the pillar shown, indicating that the crystals obtained according to Example 1 were disodium 5'-guanylate heptahydrate. Comparative Example 1 The experiments were performed in the same manner as in Example 1, except that 1.3 L of the 380 g / L aqueous solution of disodium 5'-guanylate was added instead of 0.875 L, and the sodium chloride concentration in the mixed solution was 130.4 g / L. As a result, although seed crystals were added and observed for 6 hours, no conversion of the amorphous solids to disodium 5'-guanylate heptahydrate was observed. When the temperature of the mixed solution was slowly cooled to 25°C or lower, the reaction continued. Qezfrnn / zznz / E / YiAi for two hours, the amorphous solids remained as they were and thus could not be separated by centrifugation using a basket separator. Comparative Example 2 When 0.875 L of an aqueous solution at 380 g / L of disodium 5'-guanylate was slowly added to 1 L of an aqueous solution at 300 g / L of sodium chloride at a temperature of 40°C, the pH of which was adjusted to 9 by means of 0.3 g of 5% NaOH, the non-crystalline, i.e., amorphous crystals converted to plate-like tetrahydrate crystals at a sodium chloride concentration of 160 g / L. 1% by weight of seed crystals based on the weight of disodium 5'-guanylate were added to the mixed solution of the aqueous saline and the aqueous disodium 5'-guanylate solution, while maintaining the internal temperature of the mixed solution at approximately 52°C, and crystal conversion was completed within 1 hour. However, the crystals obtained were not pillar-type heptahydrate crystals but plate-like tetrahydrate crystals. FIGURE 2 shows an image of plate-like disodium 5'-guanylate tetrahydrate crystals obtained according to Comparative Example 2, as Qezfrnn / zznz / E / YiAi were photographed by a microscope. Comparative Example 3: Crystal prepared by means of the use of an organic solvent 4.4 g of Na₂P₄ were added and completely dissolved in 1.5 L of a 200 g / L disodium 5'-guanylate solution, followed by stirring at 120 rpm at 38°C for 10 to 20 minutes. After adding 0.2 L of methanol at a flow rate of 3.4 mL / min, disodium 5'-guanylate heptahydrate seed crystals were added at a concentration of 1% by weight based on the weight of disodium 5'-guanylate in the solution. Once the system was fully equilibrated, 1 L of methanol was repeatedly added at 3.4 mL / min for a total of 5 hours to obtain pillar crystals, which weighed 259 g after dehydration. The resulting crystals were naturally dried at 25°C for 12 hours to obtain dry crystals of disodium 5'-guanylate heptahydrate. The dried crystals had a residual moisture content of 23.6% (w / v). Table 1 shows the amount of methanol used in the methods described in Example 1 and Comparative Example 3, the purity of the disodium 5'-guanylate heptahydrate crystals produced with these methods, and the remaining methanol content. In Table 1, the amount of methanol used is based on 100 g of Qezfrnn / zznz / E / YiAi 5'-guanylate disodium heptahydrate obtained. In addition, the purity (%) of the 5'-guanylate disodium heptahydrate was measured according to the method described in Example 1. The residual methanol content represents the methanol remaining in the 5% (w / v) aqueous crystal solution. Qezfrnn / zznz / E / YiAi Table 1 Amount of methanol used (g) Purity of disodium 5'-guanylate heptahydrate (%) Amount of residual methanol (ppm) Comparative Example 3 270 95.06 850 Example 1 0 95.00 Not detected As shown in Table 1, the crystals of Example 1 maintained a purity of 95% or more, which was similar to that of Comparative Example 3. Furthermore, in Comparative Example 3, 270 g of methanol were used as an organic solvent to obtain 100 g of disodium 5'-guanylate heptahydrate crystals, but no organic solvent was used in Example 1. FIGURE 3 shows an image of disodium 5'-guanylate heptahydrate crystals obtained by using methanol, a hydrophilic organic solvent according to Comparative Example 3, as photographed by a microscope. Example Assessment 1. Effect of salt concentration in the mixed solution on crystal formation In this section, the experiments were carried out in the same way as in Example 1, except that an aqueous solution of sodium chloride at 400 g / L was used instead of an aqueous solution of sodium chloride at 300 g / L and different amounts of aqueous solution of disodium 5' guanylate were added so that the concentrations of NaCl in the mixed solution were from 120 g / L to 380 g / L. As a result, the amorphous solids or crystals formed in the mixed solution were observed through a microscope. The results are shown in Table 2. Table 2 Sodium chloride concentration (g / L) Morphology of solid material Conversion time (min) 120 Amorphous solid - 140 Amorphous solid - 160 Pillar-shaped heptahydrate crystal 30 200 Pillar-shaped heptahydrate crystal 25 300 Pillar-shaped heptahydrate crystal 25 360 Pillar-shaped heptahydrate crystal 25 380 Pillar-shaped heptahydrate crystal, but the crystal is small and mixed with sodium chloride 25 As shown in Table 2, when the sodium chloride concentration in the mixed solution was 160 g / L or higher, the amorphous solid form of disodium 5'-guanylate converted to the heptahydrate. Meanwhile, when the sodium chloride concentration in the mixed solution exceeded 360 g / L, smaller crystals were obtained mixed with the sodium chloride, making it difficult to separate the disodium 5'-guanylate from the thick crystal suspension. The larger the crystal size, the easier it is to separate the disodium 5'-guanylate crystals from the thick crystal suspension. Therefore, based on the results presented in Section 2 below, it was confirmed that the disodium 5'-guanylate heptahydrate formed at salt concentrations of 160 g / L to 360 g / L in the mixed solution. Example Assessment 2. Solubility of 5'guanylic acid in the mixed solution The solubility of 5'-guanylic acid was examined by adding aqueous 5'-guanylic acid solutions to different concentrations of aqueous sodium chloride solutions at temperatures of 40°C and 25°C. Specifically, the aqueous solution of 5'-guanylic acid was sufficiently dissolved in each of the aqueous sodium chloride solutions at 40°C and 25°C, respectively, to prepare saturated solutions. As a result, saturated solutions of 160 g / L to 360 g / L of sodium chloride were prepared. As shown in Tables 3 and 4, sodium chloride crystals precipitated in Qezfrnn / zznz / E / YiAi solutions that included 400 g / L or more of sodium chloride in the mixed solution. Then, the concentrations (g / L) of 5'-guanylic acid were measured in supernatants obtained by centrifuging each of the saturated solutions, i.e., 5 of the mixed solutions. Table 3 and Table 4 show the concentrations of disodium 5'-guanylate heptahydrate in aqueous sodium chloride solutions at 40°C and 25°C, respectively. Table 3 Qezfrnn / zznz / E / YiAi Sodium chloride concentration (g / L) 160 200 230 280 300 310 350 360 400 higher than 400 5'Guanilic acid concentration in mixed solution (g / L) 86.5 62.7 57.1 50.1 49.9 49.5 48.9 49.8 49.6 Precipitated sodium chloride crystals 48.7 Precipitated sodium chloride crystals Table 4 Sodium chloride concentration (g / L) 160 200 230 280 300 310 350 360 400 420 5'Guanilic acid concentration in the mixed solution (g / L) 40.1 26.4 22.2 19.2 18.1 18.2 18.2 18.2 18.3 Sodium chloride crystals precipitated 18.2 Sodium chloride crystals precipitated As shown in Tables 3 and 4, it was confirmed that disodium 5'-guanylate heptahydrate has low solubility in each aqueous sodium chloride solution of 160 g / L to 360 g / L, for example, from 160 g / L to 360 g / L. Meanwhile, disodium 5'-guanylate heptahydrate dissolved in each aqueous sodium chloride solution less than 160 g / L without maintaining the pillar shape. Example Assessment 3. Effect of the temperature of the mixed solution on crystal formation To 1 L of an aqueous solution at 300 g / L sodium chloride, the pH of which was adjusted to 9 by adding 0.3 g of 5% NaOH, 0.875 L of an aqueous solution at 380 g / L disodium 5'-guanylate was slowly added. In the mixed solution, which had a sodium chloride concentration of 160 g / L and a disodium 5'-guanylate concentration of 200 g / L, with the internal temperature maintained as shown in Table 5 below, seed crystals were added at a rate of 1% by weight, based on the weight of disodium 5'-guanylate. The crystals were examined under a microscope for the conversion of amorphous sodium 5'-guanylate solids to heptahydrate crystals. Table 5 shows the crystals obtained according to the temperature of the mixed solution. Qezfrnn / zznz / E / YiAi Table 5 Temperature (°C) Crystal Morphology Conversion Time (min) 20 Pillar Heptahydrate Crystal 180 25 Pillar Heptahydrate Crystal 80 30 Pillar heptahydrate crystal 60 35 Pillar heptahydrate crystal 42 40 Pillar heptahydrate crystal 30 45 Pillar heptahydrate crystal 25 50 Plate-like tetrahydrate crystal 30 Qezfrnn / zznz / E / YiAi As shown in Table 5, the conversion of pillar-type heptahydrate crystals was observed even at 20 °C, but it took some time. Rapid conversion of amorphous solids to heptahydrate was observed starting at 25 °C or higher. Meanwhile, amorphous solids converted to tetrahydrate at temperatures higher than 45 °C. Example Assessment 4. Effect of the amount of seed crystal added on crystal formation To 1 L of an aqueous solution at 300 g / L of sodium chloride, the pH of which was adjusted to 9 by using 0.3 g of 5% NaOH, 0.875 L of an aqueous solution at 380 g / L of disodium 5'-guanylate were slowly added. In the mixed solution, the concentration of sodium chloride was 160 g / L, the concentration of 5'-guanylic acid was 200 g / L, and the temperature of the mixed solution was 40°C. After the amorphous solids formed, seed crystals were added as shown in Table 6 below, and the rate of crystal formation was observed using a microscope. Table 6 shows the crystals according to the amount of seed crystals added to the mixed solution. Qezfrnn / zznz / E / YiAi Table 6 Weight of seed crystal (based on 100 parts by weight of sodium 5'-guanylate) Crystal morphology Conversion time (min) 0.05 Pillar heptahydrate crystal 80 0.1 Pillar heptahydrate crystal 60 0.5 Pillar heptahydrate crystal 40 1.0 Pillar heptahydrate crystal 30 2.5 Pillar heptahydrate crystal 30 5.0 Pillar heptahydrate crystal 25 5.5 Pillar heptahydrate crystal 25 As shown in Table 6, as the amount of seed crystals added increased, the time required for disodium 5'-guanylate to convert from the amorphous solid to the pillar heptahydrate tended to decrease. However, it was confirmed that when the amount of seed crystals added exceeded 5.0 parts by weight, the conversion time did not decrease further. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A method for preparing disodium 5'-guanylate heptahydrate crystals, characterized in that it comprises: mixing an aqueous saline solution and an aqueous solution of 5'-guanylic acid to form amorphous solids in a mixed solution; and adding seed crystals to the mixed solution to form disodium 5'-guanylate heptahydrate crystals, wherein the addition of the seed crystals is carried out while maintaining the temperature from 25°C to 45°C.

2. The method according to claim 1, characterized in that the salt concentration in the mixed solution is from 160 g / 1 to 360 g / 1.

3. The method according to claim 1, characterized in that the aqueous saline solution is at a pH of 7 to 10.

4. The method according to claim 1, characterized in that the salt concentration in the aqueous saline solution is from 200 g / L to 400 g / L. Qezfrnn / zznz / E / YiAi 5. The method according to claim 1, characterized in that the concentration of 5'-guanylic acid in the aqueous solution of 5'guanylic acid is from 50 g / 1 to 400 g / 1.

6. The method according to claim 1, characterized in that the aqueous solution of 5'-guanylic acid comprises those obtained by means of a microbial culture.

7. The method according to claim 1, characterized in that the seed crystals comprise disodium 5'guanylate heptahydrate crystals.

8. The method according to claim 1, characterized in that the amount of seed crystals added is from 0.1 parts by weight to 5.5 parts by weight based on 100 parts by weight of 5'guanylate.

9. The method according to claim 1, characterized in that it further comprises cooling a solution comprising the crystals formed after forming the disodium 5'guanylate heptahydrate crystals.

10. The method according to claim 9, characterized in that the cooling is carried out at 25°C or less.

11. The method according to claim 1, characterized in that the salt comprises an alkali metal salt.

12. The method according to claim 1, characterized in that the salt comprises NaCl.