A multistage continuous crystallization process for glycine crystals

Abstract

The application discloses a glycine crystal multistage continuous crystallization method, which realizes controllable nucleation and growth of glycine crystals through a multistage series connection crystallization system and gradient temperature control, and obtains glycine crystals with high purity, large particle size, uniform distribution, excellent anti-caking performance and the like, and simultaneously realizes recycling of mother liquor and reduction of production cost.

Description

Technical Field

[0001] This invention belongs to the field of chemical engineering crystallization technology, and relates to a method for refining and crystallizing glycine, specifically a multi-stage continuous crystallization method that can obtain glycine crystals with high purity, large particle size and uniform distribution. Background Technology

[0002] Glycine, chemically known as aminoacetic acid, is the simplest naturally occurring amino acid with the molecular formula C2H5NO2. It is non-toxic, highly water-soluble, and chemically stable, making it widely used in pharmaceuticals, food, feed, and chemical industries. In the pharmaceutical industry, it is used as a drug synthesis intermediate, buffer, and infusion formulation ingredient. In the food industry, it serves as a flavoring agent, preservative, and nutritional fortifier. In the chemical industry, it is used to synthesize surfactants, electroplating additives, and other fine chemicals. The mainstream industrial production methods for glycine include ammonolysis of chloroacetic acid, the Strecker process, and bio-fermentation. Regardless of the process route, crystallization is the core step in achieving product purification and separation. However, current glycine crystallization technologies generally employ intermittent crystallization, which easily leads to problems such as impure crystal form, irregular crystal habit, uneven particle size distribution, and a tendency to agglomerate. Specific technical shortcomings are analyzed below: CN120172866A discloses a method for preparing glycine using an aqueous phase, employing an aqueous solution of ammonium carbonate or ammonium bicarbonate as the ammonium source. The mixture undergoes an ammoniation reaction with chloroacetic acid and ammonia under the catalysis of hexamethylenetetramine. Through two cooling crystallization processes, the glycine product is separated from the ammonium chloride byproduct at temperature ranges of 48–53 °C and 10–15 °C, respectively. While this method simplifies the solvent system, the crystallization process lacks precise parameter control, resulting in insufficient product particle size uniformity.

[0003] CN118580155A discloses a method for producing pharmaceutical-grade glycine. Using an alkanoic organic solvent as the reaction medium, crude glycine is prepared through a two-step reaction. The crude product is then dissolved in pure water, decolorized with pharmaceutical-grade activated carbon, and crystallized by cooling to obtain the final product. The crystallization process employs a single-stage cooling mode, reducing the temperature from 75-90℃ to below 10℃ at a rate of 5-10℃ / h, followed by centrifugation and filtration. While this method meets pharmaceutical-grade purity requirements, the intermittent single-stage cooling mode makes it difficult to achieve stable control over crystal form and particle size.

[0004] CN119775154A discloses a method for preparing high-purity glycine, using monoethanolamine and water as raw materials to prepare crude glycine under the catalysis of heavy metal-modified molecular sieves, followed by purification by recrystallization in an alcohol-ether mixed solvent. The crystallization process involves stirring at 15-25°C, relying on solvent system optimization to improve purity; however, it does not involve the control of crystallization kinetic parameters, and the product's crystal habit and particle size distribution still have the risk of fluctuation.

[0005] CN222445508U discloses a purification system for glycine containing impurities. The system removes impurities through pretreatment with a decolorizing agent and an adsorbent, followed by low-temperature crystallization at 0-40℃ (optimal 10℃). Combined with mother liquor recycling, it improves resource utilization, resulting in a final product with a purity ≥99%. However, this method focuses on impurity removal and resource recovery, without optimizing key crystallization parameters such as cooling rate and crystal growth time. Therefore, it fails to address the core issues of uncontrollable crystal form and easy agglomeration.

[0006] In summary, existing glycine crystallization technologies all employ intermittent operations (including single-stage cooling crystallization and solvent recrystallization), which generally suffer from drawbacks such as uncontrollable crystal form, irregular crystal habit, wide particle size distribution, high moisture content, and easy product agglomeration. This leads to increased storage and transportation costs and makes it difficult to meet the efficiency and stability requirements of large-scale industrial production. Furthermore, although excipient-based techniques for controlling crystal habit have been applied in the crystallization of other salts, the introduction of exogenous additives into glycine, a food-grade and pharmaceutical-grade product, poses a purity risk, limiting the applicability of such technologies.

[0007] Therefore, developing a continuous glycine crystallization method that requires no exogenous additives, can stably control crystal form and particle size, has high production efficiency, and is environmentally friendly has become an urgent technical need to be addressed in this field. Summary of the Invention

[0008] To address the problems of impure crystal form, uneven particle size distribution, low production efficiency, and easy product agglomeration in existing glycine crystallization technologies, this invention provides a multi-stage continuous crystallization method for glycine crystals. Through a multi-stage tandem crystallization system and gradient temperature control, controllable nucleation and growth of glycine crystals are achieved, resulting in high-purity glycine crystals with large and uniform particle size distribution and excellent anti-agglomeration properties. At the same time, the mother liquor is recycled, reducing production costs.

[0009] To achieve this objective, the present invention adopts the following technical solution: One objective of this invention is to provide a multi-stage continuous crystallization method for glycine crystals, the continuous crystallization method comprising the following steps: (1) Under stirring conditions, glycine raw material is dissolved in deionized water and circulating mother liquor to obtain glycine raw material solution; (2) The glycine raw material solution is transported to the 3rd or 4th stage crystallization tank for crystallization. The crystal slurry suspension is discharged from the crystallization tank and enters the solid-liquid separation system. (3) In the solid-liquid separation system, the separated solids are discharged from the solid-liquid separation system, and the mother liquor enters the dissolving tank to continue to circulate.

[0010] This invention employs a multi-stage continuous crystallization process to prepare glycine crystals. By optimizing the crystal habit, achieving a narrow particle size distribution, and reducing moisture content, it effectively shortens drying time, significantly improves product flowability and bulk density, and simultaneously ensures the directional formation of the glycine α-crystal form and the maintenance of high purity. This method fully leverages the technical advantages of continuous crystallization, significantly reducing batch-to-batch variations and minimizing energy losses caused by repeated temperature fluctuations during intermittent operations, aligning with the development needs of green production and energy conservation.

[0011] This invention, for the first time, custom-designs a multi-stage continuous crystallization process specifically for the polymorphic characteristics and low viscosity of glycine. Compared to the intermittent or single-stage continuous crystallization conventionally used for other amino acids, it offers advantages such as high equipment integration, simple operation, high production efficiency, low labor costs, and significantly reduced energy consumption. Simultaneously, the product exhibits outstanding characteristics including strong stability, good batch consistency, complete and regular crystal structure, uniform and controllable particle size, and excellent application adaptability. It solves key problems in traditional glycine crystallization processes such as easy crystal agglomeration, poor growth controllability, and low efficiency in large-scale production. It meets the stringent requirements of food-grade and pharmaceutical-grade products without the need for exogenous additives, making it more suitable for large-scale industrial application.

[0012] In this invention, the method is applicable to continuous crystallization processes with 3 to 4 crystallizer stages. The number of crystallizer stages can be optimized according to actual conditions. To prevent excessive temperature gradients from causing rapid changes in supersaturation, which could lead to an increase in the aspect ratio and uneven particle size distribution of glycine crystals, a higher number of continuous crystallization stages was used in the experiment. This effectively controls the supersaturation gradient during crystallization, resulting in a higher quality product.

[0013] Preferably, when the crystallization reactor has three stages, the crystallization in step (2) includes: A1. Control the temperature of the first crystallization vessel to 25-35℃ within 1.5-3.5 h. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 h. The crystal slurry is discharged from the first crystallization vessel and enters the second crystallization vessel. A2. Control the temperature of the second crystallization vessel to 25-35℃ within 1.5-3.5 h. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 h. Then, lower the temperature to 30-40℃ within 2-4 h. The crystal slurry is discharged from the second crystallization vessel and enters the third crystallization vessel. A3. Control the temperature of the third crystallization vessel to 25-35℃ within 1.5-3.5 hours. When solids precipitate, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 15-25℃ within 5-7 hours. The crystal slurry is discharged from the third crystallization vessel.

[0014] Preferably, when the crystallization reactor has four stages, the crystallization in step (2) includes: A1. Control the temperature of the first crystallization vessel to drop to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and keep it at that temperature for 1-2 hours. The crystal slurry is discharged from the first crystallization vessel and enters the second crystallization vessel. A2. Control the temperature of the second crystallization vessel to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 35-45℃ within 1-3 hours. The crystal slurry is discharged from the second crystallization vessel and enters the third crystallization vessel. A3. Control the temperature of the third crystallization vessel to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 25-35℃ within 3-5 hours. The crystal slurry is discharged from the third crystallization vessel and enters the fourth crystallization vessel. A4. Control the temperature of the fourth crystallization vessel to 25-35℃ within 1-3 hours. When solids precipitate, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 15-25℃ within 5-7 hours. The crystal slurry is discharged from the fourth crystallization vessel.

[0015] Preferably, the stirring rate in step (1) is 200~400 r / min.

[0016] Preferably, the concentration of glycine in the glycine raw material solution in step (1) is 30-36 wt%.

[0017] Preferably, the temperature of the glycine raw material solution in step (1) is 75-85℃.

[0018] In this invention, stirring is achieved by a stirring paddle. The current stirring rate is designed for crystallizers with a volume of 1-5 L. In practical applications, the stirring rate is no longer specifically limited; the value of the stirring rate can be matched according to the volume of the specific crystallizer. The same applies to other stirring rates in this invention.

[0019] Preferably, the crystallization in step (2) is carried out under stirring conditions, and the stirring rate is 200-400 r / min.

[0020] Preferably, in step (2), the temperature rise in the first crystallizing vessel after the material is added via the dissolving vessel does not exceed 5°C; Preferably, in step (2), the temperature rise of the second, third, and fourth crystallizing vessels after the materials are added from the previous stage vessel does not exceed 3°C.

[0021] Preferably, step (3) further includes washing and vacuum drying the solid obtained from solid-liquid separation in sequence; the solvent used for washing is ethanol; the temperature of vacuum drying is 40-50℃, the time is 4-8 h, and the vacuum degree is 0.05-0.1MPa.

[0022] In this invention, the glycine crystals are in the bulk α-crystal form with a crystal purity of 100%; the average particle size is 500~800μm; and the particle size distribution Span≤1.0.

[0023] Compared with the prior art, the present invention has the following beneficial effects: (1) This invention adopts a four-stage series continuous crystallization process. Through mother liquor circulation, the overall yield of glycine can reach 100%. At the same time, by strictly controlling the operating parameters and temperature rise of each crystallizer, the blocky α crystal form of glycine is stably obtained with a crystal purity of 100%. Continuous production eliminates the parameter differences between batches. The XRD characteristic peak consistency of different batches of products is ≥99%, and the crystal stability is significantly better than that of the batch process.

[0024] (2) The glycine crystals obtained by this invention have an average particle size of 500~800μm (only 400~500μm in batch process), and a narrow particle size distribution (Span=(Dv(90)-Dv(10)) / Dv(50)≤1.0). The large-sized uniform crystals form a loose filter cake in the solid-liquid separation stage, with a filter cake moisture content of only 3-6% (7-10% in batch process), and the subsequent drying time is shortened to 60-90min (120-150min in batch process). At the same time, the uniform particle size avoids problems such as sieving blockage and uneven packaging caused by fine crystal accumulation, and the product has excellent flowability.

[0025] (3) The large particle size and narrow distribution characteristics fundamentally solve the problem of agglomeration during the drying and storage of glycine: First, the large-particle crystals adsorb less moisture and impurities on their surface, and the van der Waals forces and hydrogen bonds between particles are significantly weakened; second, the uniform particle size avoids the tight packing structure of fine crystals filling the gaps between coarse crystals, and the crystals form natural pores when stacked, reducing liquid bridge adhesion caused by moisture condensation. Experimental verification shows that the glycine product of this invention has a reduced agglomeration rate of 10~20% after drying (25~35% for batch processes), and under storage conditions of 30℃ and 45% relative humidity, after several humidity cycles, the agglomeration hardness is <1N.

[0026] (4) By recycling the mother liquor, the raw material consumption is reduced by 15% to 20% and the production cost is reduced by 25% to 30%. The continuous production efficiency is 3 to 5 times higher than that of the intermittent process, and the annual processing capacity can reach more than 5,000 tons. No external additives or organic solvents are required, and the wastewater discharge is reduced by 40% to 50%, which meets the needs of green chemical development. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the four-stage continuous crystallization process of glycine in Example 1; Figure 2 This is a schematic diagram of the three-stage continuous crystallization process of glycine in Example 4; Figure 3 An optical microscope image of the glycine crystal prepared in Example 1; Figure 4 Here is a scanning electron microscope image of the glycine crystals prepared in Example 1; Figure 5 The powder X-ray diffraction pattern of the glycine crystals prepared in Example 1; Figure 6 The particle size and particle size distribution of the glycine crystals prepared in Example 1 are shown in the figure. Figure 7 An optical microscope image of the glycine crystal prepared in comparison. Figure 8 Here is a scanning electron microscope image of the glycine crystals prepared in comparison. Figure 9 Powder X-ray diffraction pattern of glycine crystals prepared in comparison; Figure 10 The particle size and particle size distribution of glycine crystals prepared in the comparative example are shown in the figure. Figure 11 Photos of glycine products after drying, showing clumping, for Examples 1, 4, and the comparative examples; Figure 12 The results show the agglomeration strength of Examples 1, 4, and the comparative examples after storage in a constant temperature and humidity chamber for several temperature cycles. Detailed Implementation

[0028] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following embodiments are merely simple examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims. Example 1 This embodiment provides a four-stage continuous crystallization method for glycine crystals, such as... Figure 1 As shown, it includes the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, then into the third-stage reactor, and finally into the fourth-stage reactor. The crystal slurry in the fourth-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution was added from the dissolving tank to the first, second, third and fourth stage crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank was 33 wt% and the temperature of glycine solution was 80℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2 hours. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for 1.5 hours to dissolve some of the precipitated crystals. The temperature is then kept at that temperature and the process continues. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2 hours. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for 1.5 hours. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 40°C over 2 hours and kept at that temperature until the solids are released. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2 hours. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for 1.5 hours. Then, the temperature of the glycine solution in the third stage vessel is slowly reduced to 30°C over 4 hours and kept at that temperature until the crystallization vessel is ready. (5) Fourth stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2 hours. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for 1.5 hours. Then, the temperature of the glycine solution in the fourth stage vessel is slowly reduced to 20°C over 6 hours. (6) After all four crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, connect the outlet of the second-stage vessel to the inlet of the third-stage vessel, and connect the outlet of the third-stage vessel to the inlet of the fourth-stage vessel. (7) Solid-liquid separation: The crystal slurry suspension discharged from the fourth stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0029] Figure 3 and Figure 4 The images shown are optical microscope images (Olympus, CKX53, Japan) and scanning electron microscope (SEM) images (TM3000, Hitachi, Japan) of the glycine product obtained under the above operating conditions. It can be seen that the product has a large and uniform particle size, good morphology, and obvious crystal characteristics.

[0030] Figure 5 The powder diffraction pattern of the glycine product obtained under the above operating conditions (model D / MAX 2500, Japan) shows that all the obtained products are in the α crystal form.

[0031] Figure 6The particle size and particle size distribution of the glycine product obtained under the above operating conditions (MASTER SIZER3000, UK) show that the average particle size Dv(50) of the obtained product can reach 704 μm, and the particle size distribution is narrow (Span = (1100-439) / 704 = 0.94 < 1).

[0032] Example 2 This embodiment provides a four-stage continuous crystallization method for glycine crystals, comprising the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, then into the third-stage reactor, and finally into the fourth-stage reactor. The crystal slurry in the fourth-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution is added from the dissolving tank to the first, second, third and fourth stage crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank is 30 wt% and the temperature of glycine solution is 75℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C over 1 hour. When solids are clearly precipitated, the temperature is raised to 45°C and kept at that temperature for 1 hour to dissolve some of the precipitated crystals. The temperature is then kept at that temperature and the process is continued. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C for 1 hour. When solids are clearly precipitated, the temperature is raised to 45°C and kept for 1 hour. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 35°C for 1 hour and kept for a while. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C for 1 hour. When solids are clearly precipitated, the temperature is raised to 45°C and kept for 1 hour. Then, the temperature of the glycine solution in the third stage vessel is slowly reduced to 25°C for 3 hours and kept for waiting. (5) Fourth stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C for 1 hour. When solids are clearly precipitated, the temperature is raised to 45°C and kept for 1 hour. Then, the temperature of the glycine solution in the fourth stage vessel is slowly reduced to 15°C for 5 hours. (6) After all four crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, connect the outlet of the second-stage vessel to the inlet of the third-stage vessel, and connect the outlet of the third-stage vessel to the inlet of the fourth-stage vessel. (7) Solid-liquid separation: The crystal slurry suspension discharged from the fourth stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0033] Example 3 This embodiment provides a four-stage continuous crystallization method for glycine crystals, comprising the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, then into the third-stage reactor, and finally into the fourth-stage reactor. The crystal slurry in the fourth-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution was added from the dissolving tank to the first, second, third and fourth stage crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank was 36 wt% and the temperature of glycine solution was 85℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3 hours. When solids are clearly precipitated, the temperature is raised to 55°C and kept at that temperature for 2 hours to dissolve some of the precipitated crystals. The temperature is then kept at that temperature and the process continues. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3 hours. When solids are clearly precipitated, the temperature is raised to 55°C and kept for 2 hours. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 45°C over 3 hours and kept for a while. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3 hours. When solids are clearly precipitated, the temperature is raised to 55°C and kept for 2 hours. Then, the temperature of the glycine solution in the third stage vessel is slowly reduced to 35°C over 5 hours and kept for a while. (5) Fourth stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3 hours. When solids are clearly precipitated, the temperature is raised to 55°C and kept for 2 hours. Then, the temperature of the glycine solution in the fourth stage vessel is slowly reduced to 25°C over 7 hours. (6) After all four crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, connect the outlet of the second-stage vessel to the inlet of the third-stage vessel, and connect the outlet of the third-stage vessel to the inlet of the fourth-stage vessel. (7) Solid-liquid separation: The crystal slurry suspension discharged from the fourth stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0034] Example 4 This embodiment provides a three-stage continuous crystallization method for glycine crystals, such as... Figure 2 As shown, it includes the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, and the crystal slurry from the second-stage reactor is pumped into the third-stage reactor. The crystal slurry in the third-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution was added from the dissolving tank to the first, second and third stage crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank was 33 wt% and the temperature of glycine solution was 80℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2.5 h. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for more than 1.5 h to dissolve some of the precipitated crystals. Keep the temperature and wait. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2.5 h. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for more than 1.5 h. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 35°C over 3 h and kept at that temperature until the solids are released. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 30°C over 2.5 h. When solids are clearly precipitated, the temperature is raised to 50°C and kept at that temperature for more than 1.5 h. Then, the temperature of the glycine solution in the third stage vessel is slowly reduced to 20°C over 6 h. (5) After all three crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, and connect the outlet of the second-stage vessel to the inlet of the third-stage vessel.

[0035] (6) Solid-liquid separation: The crystal slurry suspension discharged from the third stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0036] Example 5 This embodiment provides a three-stage continuous crystallization method for glycine crystals, including the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, and the crystal slurry from the second-stage reactor is pumped into the third-stage reactor. The crystal slurry in the third-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution is added from the dissolving tank to the first, second and third stage crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank is 30 wt% and the temperature of glycine solution is 75℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C over 1.5 h. When solids are clearly precipitated, the temperature is raised to 45°C and kept at that temperature for more than 1 h to dissolve some of the precipitated crystals. Then, the temperature is kept at that temperature and the process is continued. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C over 1.5 h. When solids are clearly precipitated, the temperature is raised to 45°C and kept at that temperature for more than 1 h. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 30°C over 2 h and kept at that temperature until the crystallization vessel is ready. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 25°C for 1.5 h. When solids are clearly precipitated, the temperature is raised to 45°C and kept for more than 1 h. Then the temperature of the glycine solution in the third stage vessel is slowly reduced to 15°C for 5 h. (5) After all three crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, and connect the outlet of the second-stage vessel to the inlet of the third-stage vessel.

[0037] (6) Solid-liquid separation: The crystal slurry suspension discharged from the third stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0038] Example 6 This embodiment provides a three-stage continuous crystallization method for glycine crystals, including the following steps: The raw material is pumped from the dissolving tank into the first-stage reactor. The crystal slurry from the first-stage reactor is pumped into the second-stage reactor, and the crystal slurry from the second-stage reactor is pumped into the third-stage reactor. The crystal slurry in the third-stage reactor is then transported to the filtration and separation section via pumps. The specific operation is as follows: (1) Preparation of initial base solution: Glycine raw material solution was added from the dissolving tank to the first, second and third crystallization kettles as initial base solution, wherein the mass concentration of glycine solution in the dissolving tank was 36 wt% and the temperature of glycine solution was 85℃; (2) First stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3.5 h. When solids are clearly precipitated, the temperature is raised to 55°C and kept at that temperature for more than 2 h to dissolve some of the precipitated crystals. Then, the temperature is kept at that temperature and the process is continued. (3) Second stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3.5 h. When solids are clearly precipitated, the temperature is raised to 55°C and kept at that temperature for more than 2 h. Then, the temperature of the glycine solution in the second stage vessel is slowly reduced to 40°C over 4 h and kept at that temperature until the solids are released. (4) Third stage crystallization: The temperature of the glycine solution in the crystallization vessel is slowly reduced to 35°C over 3.5 h. When solids are clearly precipitated, the temperature is raised to 55°C and kept for more than 2 h. Then, the temperature of the glycine solution in the third stage vessel is slowly reduced to 25°C over 7 h. (5) After all three crystallization vessels have reached the specified temperature, connect the outlet of the first-stage vessel to the inlet of the second-stage vessel, and connect the outlet of the second-stage vessel to the inlet of the third-stage vessel.

[0039] (6) Solid-liquid separation: The crystal slurry suspension discharged from the third stage reactor is separated by a solid-liquid separator to obtain glycine crystals, which are then dried to obtain glycine crystal products.

[0040] Comparative Example The traditional cooling crystallization process uses a crystallization vessel, and the specific steps are as follows: a 33wt% glycine solution is prepared into the crystallization vessel and heated to dissolve it. The temperature is controlled at 80℃ to obtain a clear liquid. Then, it is slowly cooled to 20℃ for 4 hours to obtain a glycine crystal slurry suspension. After passing through a solid-liquid separator, glycine crystals are obtained. After drying, glycine crystal products are obtained.

[0041] Figure 7 and Figure 8 The images shown are optical microscope images and scanning electron microscope (SEM) images of the glycine products obtained under the above operating conditions. It can be seen that the product has a small particle size and uneven distribution, poor morphology, and obvious agglomeration of small crystals.

[0042] Figure 9 The powder diffraction pattern of the glycine product obtained under the above operating conditions shows that the product is an α+γ mixed crystal, and most of it is γ crystal form.

[0043] Figure 10 The particle size and particle size distribution of the glycine product obtained under the above operating conditions show that the average particle size Dv(50) of the obtained product is only 443 μm, and the particle size distribution is wide (Span = (771-231) / 443 = 1.22>1).

[0044] Figure 11 The images show agglomeration photos of the glycine products after drying, for Examples 1, 4, and the comparative example, respectively. The agglomeration rates of the products after filtration were 3.31%, 16.23%, and 30.25%, respectively. Example 1 exhibits excellent crystallinity, large particle size, and narrow particle size distribution, significantly reducing the moisture content of the filter cake and demonstrating strong anti-agglomeration properties. Furthermore, the agglomerates formed during the drying process are very loose, and the tumbling and stirring operations during the drying process ensure that the final product is free of agglomeration.

[0045] Figure 12 The agglomeration strength results for Examples 1, 4, and the comparative example after several temperature cycles in a constant temperature and humidity chamber (30°C, 45% relative humidity) are shown. The Max value represents the pressure applied when the press crushes the agglomerated product; higher pressure indicates a stronger agglomerate, meaning the product is more prone to agglomeration. The figure shows that the pressures measured for Examples 1, 4, and the comparative example are 0.7, 1.0, and 2.3, respectively. This indicates that the agglomeration phenomenon in Example 1 is significantly reduced compared to the comparative example.

[0046] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A multi-stage continuous crystallization method for glycine crystals, characterized in that, The multi-stage continuous crystallization method includes the following steps: (1) Under stirring conditions, glycine raw material is dissolved in deionized water and circulating mother liquor to obtain glycine raw material solution; (2) The glycine raw material solution is transported to the 3-4 stage crystallization kettle for crystallization. The crystal slurry suspension is discharged from the crystallization kettle and enters the solid-liquid separation system. (3) In the solid-liquid separation system, the separated solids are discharged from the solid-liquid separation system, and the mother liquor enters the dissolving tank to continue to circulate.

2. The multi-stage continuous crystallization method according to claim 1, characterized in that, When the crystallization vessel has three stages, the crystallization in step (2) includes: A1. Control the temperature of the first crystallization vessel to 25-35℃ within 1.5-3.5 h. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 h. The crystal slurry is discharged from the first crystallization vessel and enters the second crystallization vessel. A2. Control the temperature of the second crystallization vessel to 25-35℃ within 1.5-3.5 h. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 h. Then, lower the temperature to 30-40℃ within 2-4 h. The crystal slurry is discharged from the second crystallization vessel and enters the third crystallization vessel. A3. Control the temperature of the third crystallization vessel to 25-35℃ within 1.5-3.5 hours. When solids precipitate, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 15-25℃ within 5-7 hours. The crystal slurry is discharged from the third crystallization vessel.

3. The multi-stage continuous crystallization method according to claim 1, characterized in that, When the crystallization vessel has four stages, the crystallization in step (2) includes: A1. Control the temperature of the first crystallization vessel to drop to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and keep it at that temperature for 1-2 hours. The crystal slurry is discharged from the first crystallization vessel and enters the second crystallization vessel. A2. Control the temperature of the second crystallization vessel to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 35-45℃ within 1-3 hours. The crystal slurry is discharged from the second crystallization vessel and enters the third crystallization vessel. A3. Control the temperature of the third crystallization vessel to 25-35℃ within 1-3 hours. When solid precipitates, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 25-35℃ within 3-5 hours. The crystal slurry is discharged from the third crystallization vessel and enters the fourth crystallization vessel. A4. Control the temperature of the fourth crystallization vessel to 25-35℃ within 1-3 hours. When solids precipitate, raise the temperature to 45-55℃ and hold for 1-2 hours. Then, lower the temperature to 15-25℃ within 5-7 hours. The crystal slurry is discharged from the fourth crystallization vessel.

4. The multi-stage continuous crystallization method according to claim 1, characterized in that, The stirring rate in step (1) is 200-400 r / min; Preferably, the concentration of glycine in the glycine raw material solution in step (1) is 30-36 wt%; Preferably, the temperature of the glycine raw material solution in step (1) is 75-85℃.

5. The multi-stage continuous crystallization method according to claim 1, characterized in that, The crystallization in step (2) is carried out under stirring conditions, and the stirring rate is 200-400 r / min.

6. The multi-stage continuous crystallization method according to claims 1-3, characterized in that, The temperature rise in the first crystallization vessel after the material is added via the dissolving vessel does not exceed 5°C; the temperature rise in the second, third, and fourth crystallization vessels after the material is added via the previous stage vessel does not exceed 3°C.

7. The multi-stage continuous crystallization according to claim 1, characterized in that, Step (3) further includes washing and vacuum drying the solid obtained from solid-liquid separation in sequence; Preferably, the cleaning solvent is ethanol; Preferably, the vacuum drying temperature is 40-60℃, the time is 4-8 h, and the vacuum degree is 0.05-0.1 MPa.

8. Preparation of glycine crystals by multi-stage continuous crystallization according to any one of claims 1-7; The glycine crystals are in bulk α-crystal form with a crystal purity of 100%. The glycine crystals have an average particle size of 500-800 μm; The glycine crystals have a particle size distribution of Span ≤ 1.

0.

9. The application of glycine according to claim 8 in drug preparation and food additives.

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