Crystallization method of adenylic acid

Abstract

The invention belongs to the technical field of crystallization, and relates to a crystallization method of adenylic acid. A crystallization method of adenylic acid comprises the following steps: mixing an adenylic acid crude product with water, and adjusting the pH value to obtain an adenylic acid aqueous solution; adjusting the temperature and the stirring rotating speed of the adenylic acid aqueous solution crystallization system, adding an acid solution into the crystallization system, stopping adding the acid solution when the crystallization system is turbid, and starting to grow crystals for the first time; in the first-time crystal growing process, the temperature of a crystallization system is reduced, and the stirring rotating speed is synchronously reduced; after the first-time crystal growing is finished, keeping the temperature and the stirring rotating speed unchanged, continuously adding the acid solution into the crystallization system, and stopping adding the acid solution until the pH value of the crystallization system reaches a target pH value; cooling the temperature of the crystallization system, and stirring for secondary crystal growing; after the second time of crystal growing is finished, solid-liquid separation and drying are conducted, adenylic acid crystals are obtained, and the obtained adenylic acid crystals are large in particle, good in fluidity and high in purity.

Description

Technical Field

[0001] The invention belongs to the technical field of crystallization and relates to a crystallization method of adenylic acid. Background Art

[0002] With the development of the biotechnology and pharmaceutical industries, the research and development of nucleotides and their derivatives has become a hot topic, gradually becoming another major industry after amino acids. Nucleotides are a class of high-value-added biochemical substances with a wide range of applications, supporting the development of several major industries, such as high-end dairy and pharmaceuticals.

[0003] Adenosine mononucleotide (AMP) is one of the four main mononucleotides that make up ribonucleic acid in animal cells. It is clinically used to treat disseminated sclerosis, porphyria, pruritus, liver disease, and varicose ulcer complications, exhibiting significant peripheral vasodilation and antihypertensive effects. Adenosine mononucleotide (AMP) is an ingestible substance and can be used as an intermediate in the production of nucleic acid-based pharmaceuticals, health foods, and biochemical reagents. It is also used in the manufacture of adenosine triphosphate (ATP) and cyclic AMP (cyclic AMP). Industrially produced adenosine mononucleotide (AMP) has a relatively small particle size, is prone to aggregation, and is difficult to centrifuge. Salt impurities carried over from the mother liquor may not be completely removed, and the product is prone to harboring impurities and difficult to dry, resulting in the finished product being too fine and appearing as a fine powder. Consequently, the adenosine mononucleotide product content and yield obtained using traditional recrystallization methods are also relatively low. Therefore, it is particularly important to develop a method for preparing nucleotide crystals that can produce large, fluid, and high-purity nucleotides. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a preparation method for nucleotide crystals with large particles, good fluidity and high purity, in response to the problems existing in the adenylate crystallization process in the prior art.

[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 method for crystallizing adenylic acid, comprising the following steps: (1) Mixing crude adenylic acid with water and adjusting the pH to obtain an adenylic acid aqueous solution; (2) Adjusting the temperature and stirring speed of the adenylic acid aqueous solution crystallization system, while adding an acidic solution to the crystallization system. When the crystallization system becomes turbid, stop adding the acidic solution and start the first crystal growth. During the first crystal growth process, cool the crystallization system and simultaneously reduce the stirring speed. (3) After the first crystal growth is completed, keep the temperature and stirring speed unchanged and continue to add acidic solution to the crystallization system until the pH of the crystallization system reaches the target pH value, then stop adding acidic solution; (4) The temperature of the crystallization system is lowered and stirred for a second crystal growth; after the second crystal growth is completed, the solid-liquid separation and drying are performed to obtain adenylate crystals.

[0006] In some embodiments, in step (1), the pH is adjusted to 6.0-8.0 using an aqueous sodium hydroxide solution; and / or the concentration of the crude adenylate relative to the aqueous adenylate solution is 100-400 g / L.

[0007] In some embodiments, preferably, in step (1), the pH is adjusted to 7.0 using an aqueous sodium hydroxide solution; and / or the concentration of the crude adenylate relative to the aqueous adenylate solution is 200-300 g / L, more preferably 250 g / L.

[0008] The concentration of sodium hydroxide in the sodium hydroxide aqueous solution used is 1-10 mol / L, preferably 1-5 mol / L, more preferably 2-4 mol / L, and even more preferably 3 mol / L.

[0009] In some embodiments, in step (2), the temperature and stirring speed of the adenylic acid aqueous solution crystallization system are adjusted to adjust the temperature of the adenylic acid aqueous solution crystallization system to 30-45° C., and the stirring speed of the adenylic acid aqueous solution crystallization system is adjusted to 150-300 rpm.

[0010] In some embodiments, preferably, in step (2), the temperature and stirring speed of the adenylic acid aqueous solution crystallization system are adjusted to adjust the temperature of the adenylic acid aqueous solution crystallization system to 30-35° C., and the stirring speed of the adenylic acid aqueous solution crystallization system to 200-300 rpm.

[0011] In some embodiments, it is further preferred that in step (2), the temperature and stirring speed of the adenylic acid aqueous solution crystallization system are adjusted to adjust the temperature of the adenylic acid aqueous solution crystallization system to 30-33° C., and the stirring speed of the adenylic acid aqueous solution crystallization system is adjusted to 220-280 rpm.

[0012] In some embodiments, it is further preferred that in step (2), the temperature and stirring speed of the adenylic acid aqueous solution crystallization system are adjusted to adjust the temperature of the adenylic acid aqueous solution crystallization system to 32° C., and the stirring speed of the adenylic acid aqueous solution crystallization system to 250 rpm.

[0013] In some embodiments, in step (2), the acidic solution is any one of a hydrochloric acid aqueous solution or a sulfuric acid aqueous solution, or a combination of both; and / or, the concentration of the acid in the acidic solution is 1 to 5 mol / L.

[0014] In some embodiments, preferably, in step (2), the acidic solution is an aqueous hydrochloric acid solution; and / or the concentration of the acid in the acidic solution is 2-5 mol / L, more preferably 3 mol / L.

[0015] Wherein, in step (2), the acidic solution is added to the crystallization system at a rate of 1-10 mL / h, preferably 2-6 mL / h, more preferably 3-5 mL / h, and even more preferably 4 mL / h.

[0016] In some embodiments, in step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled down to 5-18°C and the stirring speed is uniformly reduced to 100-150 rpm.

[0017] In some embodiments, preferably, in step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled down to 10-18°C and the stirring speed is uniformly reduced to 100-150 rpm.

[0018] In some embodiments, it is further preferred that in step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled down to 13-18°C and the stirring speed is uniformly reduced to 100-120 rpm.

[0019] In some embodiments, it is further preferred that in step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled down to 15°C and the stirring speed is simultaneously uniformly reduced to 100 rpm.

[0020] Wherein, in step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled from 30~45°C to 5~18°C within 2~8 hours, and the stirring speed is uniformly reduced from 150~300 rpm to 100~150 rpm within 2~8 hours.

[0021] In some embodiments, in step (2), the first crystal growing time is 2 to 8 hours.

[0022] In some embodiments, preferably, in step (2), the first crystal growing time is 2 to 5 h, more preferably 2 to 4 h, and even more preferably 3 h.

[0023] In some embodiments, in step (3), the acidic solution is any one of a hydrochloric acid aqueous solution or a sulfuric acid aqueous solution, or a combination of both; and / or the concentration of the acid in the acidic solution is 1 to 5 mol / L; and / or the target pH value is 1.6 to 2.4.

[0024] In some embodiments, preferably, in step (3), the acidic solution is an aqueous hydrochloric acid solution; and / or the concentration of the acid in the acidic solution is 2-5 mol / L; and / or the target pH value is 1.6-2.2.

[0025] In some embodiments, it is further preferred that in step (3), the acidic solution is an aqueous hydrochloric acid solution; and / or the concentration of the acid in the acidic solution is 3 mol / L; and / or the target pH value is 1.8.

[0026] Wherein, in step (3), the temperature and stirring speed are kept unchanged, the temperature is 5~18°C, and the stirring speed is 100~150 rpm.

[0027] Wherein, preferably, in step (3), the temperature and stirring speed are kept unchanged, the temperature is 10~18°C, and the stirring speed is 100~150 rpm.

[0028] Among them, it is further preferred that in step (3), the temperature and stirring speed are kept unchanged, the temperature is 13~18°C, and the stirring speed is 100~120 rpm.

[0029] Among them, it is further preferred that in step (3), the temperature and stirring speed are kept unchanged, the temperature is 15° C., and the stirring speed is 100 rpm.

[0030] In some embodiments, in step (4), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 0~10°C.

[0031] In some embodiments, preferably, in step (4), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 4-10°C.

[0032] In some embodiments, it is further preferred that in step (4), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 6-10°C.

[0033] In some embodiments, it is further preferred that in step (4), the temperature of the crystallization system is cooled, and the specific operation is: cooling the temperature of the crystallization system to 8°C.

[0034] Wherein, in step (4), 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.

[0035] Wherein, in step (4), the crystal growing temperature in the second crystal growing is always lower than the crystal growing temperature in the first crystal growing.

[0036] In some embodiments, in step (4), the stirring is performed for the second crystal growth, and the stirring speed is 100~150rpm.

[0037] In some embodiments, preferably, in step (4), the stirring is performed for the second crystal growth, and the stirring speed is 100-120 rpm.

[0038] In some embodiments, it is further preferred that in step (4), the stirring is performed for the second crystal growth, and the stirring speed is 100 rpm.

[0039] In some embodiments, in step (4), the second crystal growing time is 1 to 10 hours.

[0040] In some embodiments, preferably, in step (4), the second crystal growing time is 1 to 5 hours.

[0041] In some embodiments, it is further preferred that in step (4), the second crystal growing time is 1 to 3 hours.

[0042] In some embodiments, more preferably, in step (4), the second crystal growing time is 2 hours.

[0043] Beneficial effects: (1) In the crystallization method of crude adenylate provided by the present invention, a variable temperature and variable stirring speed crystal growing method is introduced during the adenylate crystallization process, and the obtained adenylate crystals have large particles, good fluidity and high purity.

[0044] (2) The crystallization method of adenylate crystals provided by the present invention is simple and easy to operate, and the industrial scale-up conversion is simple, and is suitable for large-scale industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] 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.

[0046] Figure 1 This is an electron microscope image of the adenylate crystals prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0047] 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.

[0048] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials are commercially available unless otherwise specified.

[0049] The crude adenylate used in the examples of the present invention was obtained from Nanjing Tongkai Zhaoye Biotechnology Co., Ltd., with an average particle size of 68 μm and a purity of 95.6%.

[0050] Method for detecting the average particle size of crystals: detection by particle size distribution instrument.

[0051] Crystal purity detection method: high performance liquid chromatography.

[0052] Example 1: 200 g of crude adenylic acid was mixed with water, and the pH was adjusted to 7.0 with a 3 mol / L sodium hydroxide aqueous solution. The mixture was stirred and dissolved, and water was added to the volume to prepare 800 mL of a 250 g / L adenylic acid aqueous solution, which was placed in a crystallizer. The temperature of the adenylic acid aqueous solution crystallization system was adjusted to 32° C., the stirring speed was 250 rpm, and 3 mol / L hydrochloric acid aqueous solution was added dropwise to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution became turbid, the addition of hydrochloric acid aqueous solution was stopped and the first crystal growth was started for 3 h. During this first crystal growth period, the temperature of the crystallization system was uniformly cooled from 32° C. to 15° C. (completed in 3 h), and the stirring speed was simultaneously reduced from 250 rpm to 100 rpm (completed in 3 h). After the first crystal growth was completed, 3 mol / L hydrochloric acid aqueous solution was continued to be added dropwise to the crystallization system at a temperature of 15° C. and a stirring speed of 100 rpm at a rate of 4 mL / h. mol / L hydrochloric acid aqueous solution was added until the pH of the crystallization system reached 1.8, after which the addition of the hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 100 rpm for 2 h for the second crystal growth. After the second crystal growth was completed, the solid-liquid separation was performed and the product was dried at 40°C for 4 h to obtain the adenylate crystal product.

[0053] The adenylate crystal sample was tested and found to have an average particle size of 172 μm and a purity of 99.6%.

[0054] The electron microscope image of the adenylate crystals prepared in Example 1 is as follows: Figure 1 shown.

[0055] Example 2: 200 g of crude adenylic acid was mixed with water, and the pH was adjusted to 7.0 with a 3 mol / L sodium hydroxide aqueous solution. The mixture was stirred and dissolved, and water was added to the volume to prepare 800 mL of a 250 g / L adenylic acid aqueous solution, which was placed in a crystallizer. The temperature of the adenylic acid aqueous solution crystallization system was adjusted to 32° C., the stirring speed was 250 rpm, and 3 mol / L hydrochloric acid aqueous solution was added dropwise to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution became turbid, the addition of hydrochloric acid aqueous solution was stopped and the first crystal growth was started for 2 h. During this first crystal growth period, the temperature of the crystallization system was uniformly cooled from 32° C. to 15° C. (completed in 2 h), and the stirring speed was simultaneously uniformly reduced from 250 rpm to 100 rpm (completed in 2 h). After the first crystal growth was completed, 3 mol / L hydrochloric acid aqueous solution was continued to be added dropwise to the crystallization system at a temperature of 15° C. and a stirring speed of 100 rpm at a rate of 4 mL / h. mol / L hydrochloric acid aqueous solution was added until the pH of the crystallization system reached 1.8, after which the addition of the hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 100 rpm for 2 h for the second crystal growth. After the second crystal growth was completed, the solid-liquid separation was performed and the product was dried at 40°C for 4 h to obtain the adenylate crystal product.

[0056] The adenylate crystal sample was tested and found to have an average particle size of 163 μm and a purity of 99.2%.

[0057] Example 3: 200 g of crude adenylic acid was mixed with water, and the pH was adjusted to 7.0 with a 3 mol / L sodium hydroxide aqueous solution. The mixture was stirred and dissolved, and water was added to the volume to prepare 800 mL of a 250 g / L adenylic acid aqueous solution, which was placed in a crystallizer. The temperature of the adenylic acid aqueous solution crystallization system was adjusted to 32° C., the stirring speed was 250 rpm, and 3 mol / L hydrochloric acid aqueous solution was added dropwise to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution became turbid, the addition of hydrochloric acid aqueous solution was stopped and the first crystal growth was started for 4 h. During this first crystal growth period, the temperature of the crystallization system was uniformly cooled from 32° C. to 15° C. (completed in 4 h), and the stirring speed was simultaneously reduced from 250 rpm to 100 rpm (completed in 4 h). After the first crystal growth was completed, 3 mol / L hydrochloric acid aqueous solution was continued to be added dropwise to the crystallization system at a temperature of 15° C. and a stirring speed of 100 rpm at a rate of 4 mL / h. mol / L hydrochloric acid aqueous solution was added until the pH of the crystallization system reached 1.8, after which the addition of the hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 100 rpm for 2 h for the second crystal growth. After the second crystal growth was completed, the solid-liquid separation was performed and the product was dried at 40°C for 4 h to obtain the adenylate crystal product.

[0058] The adenylate crystal sample was tested and found to have an average particle size of 162 μm and a purity of 99.3%.

[0059] Comparative Example 1: Growing crystals without lowering the temperature or stirring 200 g of crude adenylic acid was mixed with water, and the pH was adjusted to 7.0 with a 3 mol / L sodium hydroxide aqueous solution. The solution was stirred and dissolved, and water was added to the volume to prepare 800 mL of a 250 g / L adenylic acid aqueous solution, which was placed in a crystallizer. The temperature of the adenylic acid aqueous solution crystallization system was adjusted to 32°C, the stirring speed was 250 rpm, and 3 mol / L hydrochloric acid aqueous solution was added dropwise to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution became turbid, the addition of hydrochloric acid aqueous solution was stopped and the first crystal growth was started for 3 h. During this first crystal growth period, the temperature and stirring speed of the crystallization system remained unchanged (temperature 32°C, stirring speed 250 rpm). After the first crystal growth was completed, 3 mol / L hydrochloric acid aqueous solution was continued to be added dropwise to the crystallization system at a rate of 4 mL / h at a temperature of 32°C and stirring at 250 rpm until the pH of the crystallization system reached 1.8, after which the addition of hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 250 rpm for 2 h. h for the second crystal growth; after the second crystal growth, the solid-liquid separation was carried out and the product was dried at 40 ° C for 4 h to obtain the adenylate crystal product.

[0060] The adenylate crystal sample was tested and found to have an average particle size of 93 μm and a purity of 97.2%.

[0061] Comparative Example 2: Only lowering the temperature during crystal growth Take 200 g of crude adenylic acid and mix it with water, adjust the pH to 7.0 with 3 mol / L sodium hydroxide aqueous solution, stir to dissolve, add water to make up to 800 mL of adenylic acid aqueous solution with a concentration of 250 g / L, and place it in a crystallizer; adjust the temperature of the adenylic acid aqueous solution crystallization system to 32°C, stir at a speed of 250 rpm, and at the same time, add 3 mol / L hydrochloric acid aqueous solution to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution becomes turbid, stop adding hydrochloric acid aqueous solution and start the first crystal growth for 3 hours. During this first crystal growth period, the temperature of the crystallization system is uniformly cooled from 32°C to 15°C (completed in 3 hours), and the stirring speed remains unchanged (stirring speed 250 rpm); after the first crystal growth is completed, continue to add 3 mol / L hydrochloric acid aqueous solution to the crystallization system at a rate of 4 mL / h at a temperature of 15°C and a stirring speed of 250 rpm. mol / L hydrochloric acid aqueous solution was added until the pH of the crystallization system reached 1.8, after which the addition of hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 250 rpm for 2 h for the second crystal growth. After the second crystal growth was completed, the solid-liquid separation was performed and the product was dried at 40°C for 4 h to obtain adenylate crystal product.

[0062] The adenylate crystal sample was tested and found to have an average particle size of 127 μm and a purity of 98.5%.

[0063] Comparative Example 3: Only the stirring speed is reduced during the crystal growth process 200 g of crude adenylic acid was mixed with water and the pH was adjusted to 7.0 with 3 mol / L sodium hydroxide aqueous solution. The mixture was stirred and dissolved, and water was added to the volume to prepare 800 mL of adenylic acid aqueous solution with a concentration of 250 g / L, which was placed in a crystallizer. The temperature of the adenylic acid aqueous solution crystallization system was adjusted to 32°C, the stirring speed was 250 rpm, and 3 mol / L hydrochloric acid aqueous solution was added dropwise to the crystallization system at a rate of 4 mL / h. When the adenylic acid aqueous solution became turbid, the addition of hydrochloric acid aqueous solution was stopped and the first crystal growth was started for 3 h. The temperature was kept constant at 32°C, and the stirring speed was uniformly reduced from 250 rpm to 100 rpm (completed in 3 h). After the first crystal growth was completed, 3 mol / L hydrochloric acid aqueous solution was continued to be added dropwise to the crystallization system at a rate of 4 mL / h at a temperature of 32°C and stirring at 100 rpm until the pH of the crystallization system reached 1.8, after which the addition of hydrochloric acid aqueous solution was stopped. The temperature of the crystallization system was then directly and rapidly cooled to 8°C and maintained at 8°C and 100 rpm for 2 h. h. Carry out the second crystal growth; after the second crystal growth is completed, separate the solid and liquid and dry to obtain the adenylate crystal product.

[0064] The adenylate crystal sample was tested and found to have an average particle size of 32 μm and a purity of 98.7%.

[0065] The present invention provides a method and concept for crystallizing adenosine monophosphate. Numerous methods and approaches exist 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 adenylic acid, characterized in that: The steps include: (1) Mixing crude adenylic acid with water and adjusting the pH to obtain an adenylic acid aqueous solution; (2) Adjust the temperature and stirring speed of the adenylic acid aqueous solution crystallization system, and add acidic solution to the crystallization system at the same time. When the crystallization system becomes turbid, stop adding acidic solution and start the first crystal growth; During the first crystal growth process, the temperature of the crystallization system is lowered and the stirring speed is simultaneously reduced; (3) After the first crystal growth is completed, keep the temperature and stirring speed unchanged and continue to add acidic solution to the crystallization system until the pH of the crystallization system reaches the target pH value, then stop adding acidic solution; (4) The temperature of the crystallization system is lowered and stirred for a second crystal growth; after the second crystal growth is completed, the solid-liquid separation and drying are performed to obtain adenylate crystals.

2. The method according to claim 1, characterized in that In step (1), the pH is adjusted to 6.0-8.0 using a sodium hydroxide aqueous solution; and / or the concentration of the crude adenylate relative to the adenylate aqueous solution is 100-400 g / L.

3. The method according to claim 1, characterized in that In step (2), the temperature and stirring speed of the adenylic acid aqueous solution crystallization system are adjusted to adjust the temperature of the adenylic acid aqueous solution crystallization system to 30-45° C., and the stirring speed of the adenylic acid aqueous solution crystallization system is adjusted to 150-300 rpm.

4. The method according to claim 1, wherein In step (2), the acidic solution is any one of a hydrochloric acid aqueous solution or a sulfuric acid aqueous solution, or a combination of both; and / or, the concentration of the acid in the acidic solution is 1 to 5 mol / L.

5. The method according to claim 1, wherein In step (2), during the first crystal growing process, the temperature of the crystallization system is cooled down and the stirring speed is simultaneously reduced. The specific operation is: the temperature of the crystallization system is uniformly cooled to 5~18°C and the stirring speed is uniformly reduced to 100~150 rpm.

6. The method according to claim 1, characterized in that In step (2), the first crystal growing time is 2 to 8 hours.

7. The method according to claim 1, characterized in that In step (3), the acidic solution is any one of a hydrochloric acid aqueous solution or a sulfuric acid aqueous solution, or a combination of both; and / or the acid concentration in the acidic solution is 1 to 5 mol / L; and / or the target pH value is 1.6 to 2.

4.

8. The method according to claim 1, characterized in that In step (4), the temperature of the crystallization system is lowered, and the specific operation is: lowering the temperature of the crystallization system to 0~10°C.

9. The method according to claim 1, characterized in that In step (4), the stirring is performed for the second crystal growth, and the stirring speed is 100-150 rpm.

10. The method according to claim 1, characterized in that In step (4), the second crystal growing time is 1 to 10 hours.

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