Crystallization method of disodium guanylate
By removing impurities through electrodialysis and controlling the temperature and stirring speed during the crystallization process, the problems of low purity and bulk density of disodium guanylate crystals in traditional methods are solved, and the preparation of high-purity and high-bulk-density disodium guanylate crystals is achieved, which is suitable for large-scale production.
Patent Information
- Application Number
- CN202510924111.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-04
- Publication Date
- 2025-09-05
AI Technical Summary
It is difficult to obtain high-purity, high-quality disodium guanylate crystals through traditional dissolution crystallization methods in the existing technology, especially in controlling the crystallization process.
After impurities are removed by electrodialysis, impurity ions are removed by electrodialysis in combination with the cation exchange membrane and anion exchange membrane in the electrodialysis device. Then, an antisolvent is added during the crystallization process and the temperature and stirring speed are controlled to cool the product at a uniform rate to grow the crystals. Finally, disodium guanylate crystals are obtained by solid-liquid separation.
The preparation of disodium guanylate crystals with high bulk density, good fluidity and high purity is achieved. The method is simple and easy to operate and is suitable for large-scale industrial application.
Smart Images
Figure CN120590451A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of crystallization and relates to a crystallization method of disodium guanylate. Background Art
[0002] Disodium guanylate is a food additive that appears as colorless to white crystals or a white crystalline powder. It contains approximately 7 molecules of water of crystalline water and has a savory flavor, with an umami threshold of 0.0125 g / 100 mL and an umami intensity 2.3 times that of sodium inosinate. It exhibits a strong synergistic effect when used in combination with monosodium glutamate. It is non-hygroscopic, soluble in water, and its aqueous solution is stable. It is degraded by phosphatases in acidic solutions and decomposes at temperatures between 190°C and 200°C. It is slightly soluble in ethanol and virtually insoluble in ether. Disodium guanylate is also used in the nutritional supplement and pharmaceutical industries for the preparation of nutritional supplements, metabolic regulators, and mood stabilizers. With growing domestic demand, the demand for its product quality is also increasing.
[0003] Disodium guanylate is a polyhydroxyl polar compound that tends to associate into larger molecules in alcohol-water, making the crystallization process difficult to control. Currently, traditional dissolution crystallization methods are no longer sufficient to obtain high-purity, high-quality disodium guanylate from a disodium guanylate solution. Summary of the Invention
[0004] The technical problem to be solved by the present invention is to provide a crystallization method of disodium guanylate in view of the deficiencies in the prior art, and to provide a preparation method of disodium guanylate crystals with high bulk density, good fluidity, high purity and high yield.
[0005] In order to solve the above technical problems, the technical solutions adopted by the present invention are as follows: The present invention discloses a crystallization method of disodium guanylate, comprising the following steps: (1) Mixing crude disodium guanylate with water to prepare an aqueous solution of crude disodium guanylate; (2) electrodialyzing the crude aqueous solution of disodium guanylate through an electrodialysis device. After the electrodialysis is completed, collecting the solution in the desalination chamber; (3) The solution collected in the desalination chamber is evaporated and concentrated, and the obtained solution to be crystallized is placed in a crystallizer. The temperature and stirring speed of the crystallization system are adjusted, and an anti-solvent is added to the crystallization system at the same time. When the crystallization system becomes turbid, the addition of the anti-solvent is stopped and the first crystal growth is started. During the first crystal growth process, the temperature of the crystallization system is cooled down and the stirring speed is kept constant. (4) After the first crystal growth is completed, keep the temperature and stirring speed unchanged and continue to add anti-solvent to the crystallization system until the total amount of anti-solvent added reaches 2.0~3.0 times the volume of the solution to be crystallized, then stop adding anti-solvent; (5) The temperature of the crystallization system is lowered, and the mixture is stirred for a second crystal growth. After the second crystal growth is completed, the solid-liquid separation and drying are performed to obtain disodium guanylate crystals.
[0006] In some embodiments, in step (1), the concentration of crude disodium guanylate in the crude disodium guanylate aqueous solution is 1 wt% to 5 wt%.
[0007] In some embodiments, preferably, in step (1), the concentration of crude disodium guanylate in the crude disodium guanylate aqueous solution is 1 wt% to 3 wt%, more preferably 2 wt%.
[0008] In some embodiments, in step (2), the electrodialysis voltage is 10-50 V; and / or, the electrodialysis current is 1.0-5.0 A; and / or, during the electrodialysis process, the volume ratio of the solution in the desalination chamber and the concentration chamber of the electrodialysis device is 1:(0.5-5); and / or, when the conductivity of the solution in the desalination chamber of the electrodialysis device is less than 1.0 ms / cm, the electrodialysis is stopped and the electrodialysis ends.
[0009] The purpose of the electrodialysis is to remove impurity ions in the crude aqueous solution of disodium guanylate.
[0010] Wherein, in the electrodialysis device, the cation exchange membrane is a sulfonic acid type electrodialysis cation exchange membrane, and the anion exchange membrane is a quaternary ammonium type electrodialysis anion exchange membrane.
[0011] In some embodiments, preferably, in step (2), the electrodialysis voltage is 10-30V, more preferably 20V.
[0012] In some embodiments, preferably, in step (2), the electrodialysis current is 1.0-3.0 A, more preferably 2.5 A.
[0013] In some embodiments, preferably, in step (2), during the electrodialysis process, the volume ratio of the solution in the desalting compartment and the concentrating compartment of the electrodialysis device is 1:(1-3), and more preferably 1:2.
[0014] In some embodiments, in step (3), the evaporation concentration is performed at a temperature of 30°C to 60°C; and / or, the evaporation concentration is performed at a pressure of -0.099 MPa to -0.090 MPa; and / or, in the solution to be crystallized, the concentration of the crude disodium guanylate relative to the solution to be crystallized is 25 wt% to 40 wt% based on the crude disodium guanylate.
[0015] In some embodiments, preferably, in step (3), the evaporation concentration is carried out at a temperature of 40°C to 50°C, more preferably 45°C.
[0016] In some embodiments, preferably, in step (3), the evaporation concentration has a concentration pressure of -0.095 MPa.
[0017] In some embodiments, preferably, in step (3), in the solution to be crystallized, the concentration of crude disodium guanylate relative to the solution to be crystallized is 25 wt% to 35 wt%, more preferably 30 wt%.
[0018] In some embodiments, in step (3), the temperature and stirring speed of the crystallization system are adjusted to adjust the temperature of the crystallization system of the solution to be crystallized to 20°C~45°C, and the stirring speed of the crystallization system of the solution to be crystallized to 100 rpm~300 rpm.
[0019] In some embodiments, preferably, in step (3), the temperature and stirring speed of the crystallization system are adjusted, and the temperature of the crystallization system of the solution to be crystallized is adjusted to 25°C~35°C, and the stirring speed of the crystallization system of the solution to be crystallized is adjusted to 150rpm~250rpm.
[0020] In some embodiments, it is further preferred that in step (3), the temperature and stirring speed of the crystallization system are adjusted, the temperature of the crystallization system of the solution to be crystallized is adjusted to 30° C., and the stirring speed of the crystallization system of the solution to be crystallized is adjusted to 200 rpm.
[0021] In some embodiments, in step (3), the anti-solvent is any one or a combination of methanol, ethanol, isopropanol and n-butanol; and / or, the anti-solvent is added at a rate of 5% to 15% of the volume of the solution to be crystallized / h.
[0022] Wherein, in step (3), the anti-solvents are all anhydrous solvents.
[0023] In some embodiments, preferably, in step (3), the anti-solvent is ethanol.
[0024] In some embodiments, preferably, in step (3), the anti-solvent is added at a rate of 8% to 12% of the volume of the solution to be crystallized per hour.
[0025] In some embodiments, it is further preferred that in step (3), the anti-solvent is added at a rate of 10% of the volume of the solution to be crystallized / h.
[0026] In some embodiments, in step (3), during the first crystal growing process, the temperature of the crystallization system is cooled down while the stirring speed is kept constant. Specifically, the temperature of the crystallization system is cooled down at a uniform rate to 5°C to 18°C while the stirring speed is kept constant; and / or, the crystal growing time for the first crystal growing is 2 h to 8 h.
[0027] Wherein, in step (3), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is kept unchanged. The specific operation is: the temperature of the crystallization system is cooled down from 20°C~45°C to 5°C~18°C at a uniform rate, while the stirring speed is kept unchanged, and the stirring speed is 100 rpm~300 rpm.
[0028] In some embodiments, preferably, in step (3), during the first crystal growing process, the temperature of the crystallization system is cooled down while the stirring speed is kept constant. Specifically, the temperature of the crystallization system is cooled down at a uniform rate to 10°C to 18°C while the stirring speed is kept constant; and / or, the crystal growing time for the first crystal growing is 2 h to 6 h.
[0029] In some embodiments, it is further preferred that in step (3), during the first crystal growing process, the temperature of the crystallization system is cooled down while the stirring speed is kept constant. Specifically, the temperature of the crystallization system is cooled down to 15°C at a uniform rate while the stirring speed is kept constant; and / or, the crystal growing time for the first crystal growing is 4 h.
[0030] In some embodiments, in step (4), the anti-solvent is any one or a combination of methanol, ethanol, isopropanol and n-butanol; and / or, the anti-solvent is added to the crystallization system at a rate of 5% to 15% of the volume of the solution to be crystallized / h.
[0031] Wherein, in step (4), the anti-solvents are all anhydrous solvents.
[0032] Wherein, in step (4), the total amount of the anti-solvent added reaches 2.0 to 3.0 times the volume of the solution to be crystallized, and the total amount of the anti-solvent added is the total volume of the anti-solvent added in steps (3) and (4).
[0033] In some embodiments, preferably, in step (4), the anti-solvent is ethanol.
[0034] In some embodiments, preferably, in step (4), the anti-solvent is added at a rate of 8% to 12% of the volume of the solution to be crystallized per hour.
[0035] In some embodiments, it is further preferred that in step (4), the anti-solvent is added at a rate of 10% of the volume of the solution to be crystallized / h.
[0036] In some embodiments, in step (5), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 0°C~10°C.
[0037] Wherein, in step (5), the temperature of the crystallization system is cooled down, and the cooling can be directly reduced. For example, the temperature is set to the target temperature, and the cooling device of the crystallizer is used to directly and quickly reduce the temperature without considering the cooling rate.
[0038] In some embodiments, preferably, in step (5), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 6°C~10°C.
[0039] In some embodiments, it is further preferred that in step (5), the temperature of the crystallization system is cooled, and the specific operation is: cooling the temperature of the crystallization system to 8°C.
[0040] Wherein, in step (5), the crystal growing temperature in the second crystal growing is always lower than the crystal growing temperature in the first crystal growing.
[0041] In some embodiments, in step (5), the stirring speed is 100 rpm to 300 rpm; and / or the second crystal growing time is 1 h to 10 h.
[0042] In some embodiments, preferably, in step (5), the stirring speed is 150 rpm to 250 rpm; and / or the second crystal growing time is 1 h to 6 h.
[0043] In some embodiments, it is further preferred that in step (5), the stirring speed is 150 rpm to 250 rpm; and / or the second crystal growing time is 1 h to 4 h.
[0044] In some embodiments, it is further preferred that in step (5), the stirring speed is 200 rpm; and / or the second crystal growing time is 2 h.
[0045] Beneficial effects: (1) In the crystallization method of crude disodium guanylate provided by the present invention, impurities are removed by electrodialysis and the crystals are grown by uniformly cooling during the crystallization process, thereby obtaining disodium guanylate crystals with high bulk density, good fluidity and high purity.
[0046] (2) The method provided by the present invention is simple and easy to operate, and is simple to industrially scale up and transform, and is suitable for large-scale industrial application. BRIEF DESCRIPTION OF THE DRAWINGS
[0047] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more apparent.
[0048] Figure 1This is a representative image of the disodium guanylate crystal product prepared in an embodiment of the present invention. DETAILED DESCRIPTION
[0049] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.
[0050] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials are commercially available unless otherwise specified.
[0051] 1. In the following embodiments, the method for detecting the parameters of the crystal is as follows: (1) Crystal bulk density detection method: Take a sufficient amount of powder to complete the test and pass it through a sieve with a pore size greater than 1.0 mm. Place it into a dry, graduated 250 mL graduated cylinder (readable to 2 mL) and gently, without compacting, introduce approximately 100 g (m) of the test sample to an accuracy of 0.1%. Spread the powder carefully without compacting it and read the unit volume (V) to the nearest untreated graduation. Bulk density = m / V g / mL.
[0052] 2. The bulk density and purity parameters of the crude disodium guanylate used in the following examples of the present invention are as follows: the bulk density of the crude disodium guanylate is 0.23 g / mL, and the purity is 95.3%.
[0053] 3. In the electrodialysis device used in the embodiment of the present invention, Hefei Kejia sulfonic acid type cation exchange membrane (CJMC-3, Na type) and quaternary ammonium type strong base anion exchange membrane (CJMA-3, Cl type) were selected.
[0054] Example 1: 300 g of crude disodium guanylate was taken to prepare a 2 wt % aqueous solution of crude disodium guanylate, which was stirred and dissolved. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The disodium guanylate aqueous solution obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095 MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 hours. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (4 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0055] The bulk density of the disodium guanylate crystal sample was 0.64 g / mL, the purity was 99.4%, and the yield was 97.4%.
[0056] Example 2: Changing the volume ratio of the solutions in the desalination and concentration compartments Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:1. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The aqueous solution of disodium guanylate obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095 MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (4 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0057] The bulk density of the disodium guanylate crystal sample was 0.62 g / mL, the purity was 98.9%, and the yield was 97.2%.
[0058] Example 3: Changing the volume ratio of the solutions in the desalination and concentration compartments Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:3. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The aqueous solution of disodium guanylate obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (4 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0059] The bulk density of the disodium guanylate crystal sample was 0.58 g / mL, the purity was 98.1%, and the yield was 96.5%.
[0060] Example 4: Changing the crystal growth time Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The aqueous solution of disodium guanylate obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095 MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 2 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (2 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0061] The bulk density of the disodium guanylate crystal sample was 0.60 g / mL, the purity was 98.5%, and the yield was 97.3%.
[0062] Example 5: Changing the crystal growth time Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The aqueous solution of disodium guanylate obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095 MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 6 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (6 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0063] The bulk density of the disodium guanylate crystal sample was 0.60 g / mL, the purity was 98.9%, and the yield was 97.0%.
[0064] Example 6: Changing the crystallization temperature Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The disodium guanylate aqueous solution obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (4 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 10°C, and the temperature was maintained at 10°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0065] The bulk density of the disodium guanylate crystal sample was 0.61 g / mL, the purity was 99.0%, and the yield was 96.2%.
[0066] Example 7: Changing the crystallization temperature Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The disodium guanylate aqueous solution obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 h. During the first crystal growth, the stirring was maintained at 200 rpm, and the temperature of the crystallization system was uniformly cooled from 30°C to 15°C (4 h to complete); after the first crystal growth, anhydrous ethanol was continuously added dropwise to the crystallization system at a rate of 100 mL / h at a temperature of 15°C and a stirring speed of 200 rpm. The addition of anhydrous ethanol was stopped when the total volume of the added anhydrous ethanol reached 2500 mL. The temperature of the crystallization system was then rapidly and directly cooled to 6°C and maintained at 6°C and 200 rpm for 2 h for the second crystal growth. After the second crystal growth, solid-liquid separation and drying (40°C, 4 h) were performed to obtain disodium guanylate crystal products.
[0067] The bulk density of the disodium guanylate crystal sample was 0.57 g / mL, the purity was 98.2%, and the yield was 97.4%.
[0068] Comparative Example 1: No electrodialysis, no cooling and crystal growth Take 300 g of crude disodium guanylate and prepare 1000 mL of a 30 wt% aqueous solution of crude disodium guanylate (i.e., the concentration of crude disodium guanylate in the feed solution is 300 g / L), stir and dissolve, and place in a crystallizer; adjust the temperature of the aqueous solution to 30°C, stir at 200 rpm, and at the same time, add anhydrous ethanol to the crystallization system at a rate of 100 mL / h; when turbidity appears in the crystallization system, stop adding anhydrous ethanol and start the first crystal growth for 4 hours; during the first crystal growth, keep stirring at 200 rpm and the temperature of the crystallization system at 30°C; after the first crystal growth is completed, at a temperature of 30°C and stirring at 200 rpm, continue to add anhydrous ethanol to the crystallization system at a rate of 100 mL / h, and stop adding anhydrous ethanol when the total volume of anhydrous ethanol added is 2500 mL; then quickly and directly cool the temperature of the crystallization system to 8°C, and maintain it at 8°C and 200 rpm for 2 h for the second crystal growth; after the second crystal growth, solid-liquid separation and drying (40 ° C, 4 h) were carried out to obtain disodium guanylate crystal product.
[0069] The bulk density of the disodium guanylate crystal sample was 0.32 g / mL, the purity was 97.2%, and the yield was 97.2%.
[0070] Comparative Example 2: No electrodialysis Take 300 g of crude disodium guanylate and prepare 1000 mL of a 30 wt% aqueous solution of crude disodium guanylate (i.e., the concentration of crude disodium guanylate in the feed solution is 300 g / L), stir and dissolve, and place in a crystallizer; adjust the temperature of the aqueous solution to 30°C, stir at 200 rpm, and at the same time, add anhydrous ethanol to the crystallization system at a rate of 100 mL / h; when the crystallization system becomes turbid, stop adding anhydrous ethanol and start the first crystal growth for 4 hours; during the first crystal growth, keep stirring at 200 rpm and cool the temperature of the crystallization system from 30°C to 15°C at a uniform rate (completed in 4 hours); after the first crystal growth is completed, at a temperature of 15°C and a stirring speed of 200 rpm, continue to add anhydrous ethanol to the crystallization system at a rate of 100 mL / h, and stop adding anhydrous ethanol when the total volume of anhydrous ethanol added is 2500 mL; then the temperature of the crystallization system is quickly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 hours. h for the second crystal growth; after the second crystal growth, solid-liquid separation and drying (40 ° C, 4h) were carried out to obtain disodium guanylate crystal product.
[0071] The bulk density of the disodium guanylate crystal sample was 0.46 g / mL, the purity was 98.1%, and the yield was 96.8%.
[0072] Comparative Example 3: No Cooling Take 300 g of crude disodium guanylate, prepare a 2 wt% aqueous solution of crude disodium guanylate, and stir to dissolve. Subsequently, electrodialysis was carried out at a voltage of 20 V and a current of 2.5 A, wherein a crude aqueous solution of disodium guanylate was added to the desalination chamber, and water was added to the concentration chamber. The volume ratio of the solutions in the desalination chamber and the concentration chamber was 1:2. During the electrodialysis process, the electrodialysis ended when the conductivity of the solution in the desalination chamber was lower than 1.0 ms / cm. The aqueous solution of disodium guanylate obtained from the desalination chamber was evaporated and concentrated (45°C, -0.095MPa) to a volume of 1000 mL (so that the concentration of disodium guanylate in the feed solution reached 300 g / L) and placed in a crystallizer. The temperature of the aqueous solution was adjusted to 30°C, the stirring speed was 200 rpm, and anhydrous ethanol was added dropwise to the crystallization system at a rate of 100 mL / h. When the crystallization system became turbid, the addition of anhydrous ethanol was stopped and the first crystal growth was started for 4 hours. During the first crystal growth, the stirring was maintained at 200 rpm and the temperature of the crystallization system was 30°C. After the first crystal growth was completed, the temperature was 30°C and the stirring speed was 200 rpm, continue to add anhydrous ethanol to the crystallization system at a rate of 100 mL / h, and stop adding anhydrous ethanol when the total volume of anhydrous ethanol added reaches 2500 mL; then the temperature of the crystallization system is quickly and directly cooled to 8°C, and maintained at 8°C and 200 rpm for 2 h for the second crystal growth; after the second crystal growth is completed, solid-liquid separation and drying (40°C, 4 h) are carried out to obtain disodium guanylate crystal products.
[0073] The bulk density of the disodium guanylate crystal sample was 0.43 g / mL, the purity was 98.4%, and the yield was 95.7%.
[0074] The present invention provides a method and concept for crystallizing disodium guanylate. There are numerous methods and approaches for implementing this technical solution. The foregoing merely represents a preferred embodiment of the present invention. It should be noted that those skilled in the art may make various improvements and modifications without departing from the principles of the present invention, and such improvements and modifications are also within the scope of protection of the present invention. Any components not specified in this embodiment may be implemented using existing technologies.
Claims
1. A method for crystallizing disodium guanylate, characterized in that: The steps include: (1) Mixing crude disodium guanylate with water to prepare an aqueous solution of crude disodium guanylate; (2) electrodialyzing the crude aqueous solution of disodium guanylate through an electrodialysis device. After the electrodialysis is completed, collecting the solution in the desalination chamber; (3) Evaporating and concentrating the solution collected in the desalination chamber, placing the obtained solution to be crystallized in a crystallizer, adjusting the temperature and stirring speed of the crystallization system, and adding an antisolvent to the crystallization system; When the crystallization system becomes turbid, the addition of the antisolvent is stopped and the first crystal growth is started; during the first crystal growth process, the temperature of the crystallization system is cooled down and the stirring speed is kept constant; (4) After the first crystal growth is completed, keep the temperature and stirring speed unchanged and continue to add anti-solvent to the crystallization system until the total amount of anti-solvent added reaches 2.0~3.0 times the volume of the solution to be crystallized, then stop adding anti-solvent; (5) The temperature of the crystallization system is lowered, and the mixture is stirred for a second crystal growth. After the second crystal growth is completed, the solid-liquid separation and drying are performed to obtain disodium guanylate crystals.
2. The crystallization method according to claim 1, wherein In step (1), the concentration of the crude disodium guanylate in the crude disodium guanylate aqueous solution is 1 wt% to 5 wt%.
3. The crystallization method according to claim 1, wherein In step (2), the electrodialysis voltage is 10-50 V; and / or, the electrodialysis current is 1.0-5.0 A; and / or, during the electrodialysis process, the volume ratio of the solution in the desalination chamber and the concentration chamber of the electrodialysis device is 1:(0.5-5); and / or, when the conductivity of the solution in the desalination chamber of the electrodialysis device is less than 1.0 ms / cm, the electrodialysis is stopped and the electrodialysis ends.
4. The crystallization method according to claim 1, wherein In step (3), the evaporation concentration is performed at a temperature of 30°C to 60°C; and / or the evaporation concentration is performed at a pressure of -0.099 MPa to -0.090 MPa; and / or the concentration of the crude disodium guanylate in the solution to be crystallized is 25 wt% to 40 wt% based on the crude disodium guanylate relative to the solution to be crystallized.
5. The crystallization method according to claim 1, wherein In step (3), the temperature and stirring speed of the crystallization system are adjusted, the temperature of the crystallization system of the solution to be crystallized is adjusted to 20°C~45°C, and the stirring speed of the crystallization system of the solution to be crystallized is adjusted to 100 rpm~300 rpm.
6. The crystallization method according to claim 1, characterized in that In step (3), the anti-solvent is any one or a combination of methanol, ethanol, isopropanol and n-butanol; and / or the anti-solvent is added at a rate of 5% to 15% of the volume of the solution to be crystallized / h.
7. The crystallization method according to claim 1, characterized in that In step (3), during the first crystal growing process, the temperature of the crystallization system is cooled down while the stirring speed is kept constant. Specifically, the temperature of the crystallization system is cooled down at a uniform rate to 5°C to 18°C while the stirring speed is kept constant; and / or, the crystal growing time for the first crystal growing is 2 h to 8 h.
8. The crystallization method according to claim 1, wherein In step (4), the anti-solvent is any one or a combination of methanol, ethanol, isopropanol and n-butanol; and / or, the anti-solvent is added to the crystallization system at a rate of 5% to 15% of the volume of the solution to be crystallized / h.
9. The crystallization method according to claim 1, wherein In step (5), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 0°C~10°C.
10. The crystallization method according to claim 1, characterized in that In step (5), the stirring speed is 100 rpm to 300 rpm; and / or the second crystal growing time is 1 h to 10 h.