A creatine glycine salt and its preparation method

Abstract

This invention belongs to the field of organic synthesis technology, specifically relating to a creatine glycinate and its preparation method, comprising the following steps: pretreatment, drying creatine monohydrate, passing glycine through a 100-mesh sieve and storing it in a desiccator for later use, and selecting a reaction solvent; raw material dissolution, adding the reaction solvent to a reaction vessel, starting stirring and heating, adding creatine monohydrate, and stirring at a constant temperature until completely dissolved, finally obtaining a creatine solution; complexation reaction, adding glycine, increasing the stirring rate and heating after the addition is complete, maintaining the temperature for the complexation reaction, using staged stirring until the complexation reaction is complete; after the reaction is complete, using a gradient cooling method; crystallization and ripening, followed by constant temperature and low-speed stirring for 2 hours, then allowing the crystals to settle completely; after filtration, vacuum drying is performed to finally obtain creatine glycinate. This application solves the problems of uneven reaction, poor crystal quality, and low purity and yield in existing processes, achieving efficient and high-quality preparation of creatine glycinate.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a creatine glycinate and its preparation method. Background Technology

[0002] Creatine, as an important fatigue recovery agent, is widely used in food, health products, and medicine. However, pure creatine has a bitter taste, and its solubility and crystallization stability need to be improved. Glycine, on the other hand, is the simplest natural amino acid with a sweet taste and good water solubility. It can form a complex with creatine glycinate, which can improve the taste and physicochemical properties of creatine and expand its application scenarios.

[0003] Existing processes for preparing creatine glycinate mainly involve simple raw material mixing, isothermal reaction, and direct cooling crystallization. These processes have several problems, such as hygroscopicity of creatine monohydrate and glycine agglomeration leading to uneven reaction; lack of control over stirring and heating rates during the reaction, which can easily trigger local side reactions; and direct cooling crystallization which can cause crystal agglomeration and irregular crystal forms, affecting product filtration and drying efficiency. Furthermore, existing processes lack precise design for solvent system ratios and application scenarios, making it difficult to meet the production requirements of different grades of products.

[0004] Therefore, there is an urgent need for a creatine glycine salt and its preparation method to solve the above problems. Summary of the Invention

[0005] To achieve the above objectives, this application employs the following technical solution: A method for preparing creatine glycine salt includes the following steps: Step 1, Pretreatment: Dry creatine monohydrate at 40~45℃ until the moisture content is ≤0.5%, pass it through an 80-mesh sieve, and glycine through a 100-mesh sieve. Place them in a desiccator for later use. At the same time, select a reaction solvent and the solid-liquid mass ratio of creatine monohydrate to the reaction solvent is 1:4. Step 2: Dissolve the raw materials. Add the reaction solvent to the reaction vessel, start stirring at 200-250 r / min, heat to 45-50℃, add creatine monohydrate, and stir at a constant temperature for 30 min until completely dissolved to obtain a creatine solution. Step 3, complexation reaction: add pretreated glycine to the creatine solution. The mass ratio of creatine monohydrate to glycine is 2:1. After the addition is completed, increase the stirring speed to 250~300 r / min and heat up. Keep the complexation reaction at this temperature for 2 hours. Stir in stages until the complexation reaction is complete. Step 4: Gradual cooling. After the reaction is complete, a gradient cooling process is adopted, with a total cooling time of 18-22 hours. Step 5: Crystallization and ripening, then maintain a constant temperature of 0~5℃ and stir at a low speed of 150r / min for 2 hours, then let stand for 10 minutes to allow the crystals to settle completely. Step 6: Filter, dry and sieve. After filtration, vacuum dry to finally obtain creatine glycine salt. Furthermore, the reaction solution in step 1 is one or more of water, methanol, and ethanol mixed in proportion.

[0006] Furthermore, in step 3, after the material is added, the temperature is increased to 50-55°C at a rate of 2-3°C / min.

[0007] Furthermore, in step 3, the stirring is carried out in stages with a stirring rate of 300 r / min for the first hour and 250 r / min for the last hour.

[0008] Furthermore, in step 4, the gradient cooling is as follows: first, the temperature is lowered to 25~30℃ at a rate of 5℃ / h, and then stirred at a constant temperature of 200r / min for 1h; then, the temperature is lowered to 0~5℃ at a rate of 3℃ / h, and then stirred continuously at a speed of 150~200r / min.

[0009] Compared with the prior art, the beneficial effects of this application are: 1. The technical solution in this application addresses the inherent characteristics of creatine monohydrate being hygroscopic and glycine powder being prone to agglomeration by performing targeted pretreatment on the raw materials. The pretreated raw materials have uniform particle size and good dispersibility, and can be quickly and fully dissolved in the solvent after feeding, avoiding the problem of insufficient reaction caused by raw material agglomeration and local deposition in traditional processes. This reduces the residue of unreacted raw materials from the source, and the drying treatment avoids trace side reactions caused by moisture. 2. The gradient cooling method in this application enables the crystals to grow slowly and regularly. This method avoids problems such as rapid precipitation, agglomeration, and irregular crystal form caused by sudden cooling. It enables the creatine glycinate crystals to grow slowly in a large and regular shape, which greatly improves the crystallinity of the product. At the same time, the uniform crystal morphology reduces the generation of fine crystals, making the filter cake more permeable during product filtration, making it easier to remove solvent residues, and significantly optimizing the product's flowability and solubility after drying. 3. In this application, the complexation reaction stage employs a precise control method of staged temperature control and staged stirring, which can effectively avoid the decomposition of raw materials and the generation of by-products caused by sudden temperature rise, thus ensuring the specificity of the complexation reaction. The stirring rate is dynamically adjusted according to the reaction progress, which can ensure the complete reaction while avoiding excessive stirring that would disrupt the complexation equilibrium.

[0010] This control method makes the complexation reaction more thorough and specific, with no additional byproducts generated. It not only further improves the purity of the product, but also ensures the stability of the creatine glycinate complex structure. The product retains its inherent slightly sweet taste and is completely free of the bitterness of creatine. The consistency of taste is greatly improved compared with products made by traditional processes, making it more suitable for the application scenarios of food and beverage additives. Attached Figure Description

[0011] Appendix Figure 1 This is a flowchart of the preparation method of the present invention. Detailed Implementation

[0012] The present application will be further described in conjunction with the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the scope defined by this application.

[0013] Combined with appendix Figure 1 A method for preparing creatine glycine salt, comprising the following steps: Step 1, Pretreatment: Creatine monohydrate is hygroscopic and glycine powder is prone to clumping. Direct feeding will lead to uneven reaction system. Therefore, creatine monohydrate is dried at 40~45℃ until the moisture content is ≤0.5%, passed through an 80-mesh sieve, and glycine is passed through a 100-mesh sieve. They are placed in a desiccator for later use. At the same time, one or more of water, methanol, and ethanol are selected and mixed in proportion as reaction solvent. The reaction solvent is filtered to remove impurities. The solid-liquid mass ratio of creatine monohydrate to reaction solvent is 1:4. Step 2: Dissolve the raw materials. Add the reaction solvent to the reaction vessel, start stirring at 200~250 r / min, heat to 45~50℃, add creatine monohydrate, and stir at a constant temperature for 30 min until completely dissolved. Ensure that the creatine monohydrate is completely dissolved to form a homogeneous and transparent solution to avoid local raw material deposition affecting the subsequent complexation reaction. Finally, obtain the creatine solution. Step 3, complexation reaction: Pretreated glycine is added to the creatine solution at a rate of 10 g / min. The mass ratio of creatine monohydrate to glycine is 2:1 to avoid excessive local concentration that could cause glycine agglomeration. After the addition is complete, the stirring speed is increased to 250-300 r / min, and the temperature is raised to 50-55°C at a rate of 2-3°C / min to prevent side reactions caused by sudden temperature rise. The complexation reaction is maintained at this temperature for 2 hours. At the same time, staged stirring is adopted. The stirring speed is 300 r / min in the first hour to promote sufficient contact and complexation of the raw materials, and the stirring speed is 250 r / min in the second hour to avoid excessive stirring that could disrupt the complexation equilibrium, until the system is a homogeneous and clear solution and the complexation reaction is complete. Step 4, gradient cooling: A step-by-step gradient cooling method is adopted to adapt to the crystallization and precipitation pattern of creatine glycinate. After the reaction is completed, the temperature is first cooled to 25~30℃ at a rate of 5℃ / h, and stirred at a constant temperature of 200r / min for 1h to provide a basis for uniform crystal nucleus formation. Then, the temperature is cooled to 0~5℃ at a rate of 3℃ / h, and stirred continuously at a speed of 150~200r / min to avoid local low temperature causing rapid crystal precipitation and agglomeration. The total cooling process takes 18~22h to ensure uniform crystal nucleus growth and lay the foundation for the subsequent formation of regular crystals. Step 5, crystallization and maturation: then maintain a constant temperature of 0~5℃ and stir at a low speed of 150r / min for 2 hours to allow the tiny crystal nuclei to gradually grow into large, regular crystals, reduce the formation of fine crystals, and improve the crystallinity of the product. Then let it stand for 10 minutes to allow the crystals to settle fully. Step 6: Filter, dry and sieve. After filtration, vacuum dry to finally obtain creatine glycine salt.

[0014] Example 1 A method for preparing creatine glycine salt includes the following steps: Step 1, Pretreatment: Dry 150g of creatine monohydrate at 40℃ until the moisture content is 0.4%, pass it through an 80-mesh sieve, and pass 75g of glycine through a 100-mesh sieve. Place them in a desiccator for later use. At the same time, water is selected as the reaction solvent. Step 2: Dissolve the raw materials. Add 600g of water to the reaction vessel, start stirring at 200r / min, heat to 45℃, add creatine monohydrate, and stir at a constant temperature for 30min until completely dissolved. Step 3, complexation reaction: 75g g of glycine is added to the creatine solution at a rate of 10g / min. After the addition is completed, the stirring rate is increased to 250r / min, and the temperature is increased to 50℃ at a rate of 2℃ / min. The complexation reaction is maintained at this temperature for 2h. At the same time, the stirring is carried out in stages until the complexation reaction is complete. Step 4, gradient cooling: adopt step-by-step gradient cooling, first cool down to 25℃ at a rate of 5℃ / h, stir at a constant temperature of 200r / min for 1h, then cool down to 0℃ at a rate of 3℃ / h, and continue stirring at a constant temperature of 150r / min. The total cooling process takes 18h. Step 5: Crystallization and ripening. Then, maintain a constant temperature of 0°C and stir at a low speed of 150 r / min for 2 hours. After that, let it stand for 10 minutes to allow the crystals to settle completely. Step 6: Filter, dry and sieve. After filtration, vacuum dry to obtain 185g of creatine glycinate, with a molar yield of 90% and a purity of 99.8%.

[0015] Example 2 A method for preparing creatine glycine salt includes the following steps: Step 1, Pretreatment: 150g of creatine monohydrate was dried at 42℃ to a moisture content of 0.5%, passed through an 80-mesh sieve, and 75g of glycine was passed through a 100-mesh sieve. Both were placed in a desiccator for later use. Meanwhile, methanol was selected as the reaction solvent. Step 2: Dissolve the raw materials. Add 600g of methanol to the reaction vessel, start stirring at 220r / min, heat to 48℃, add creatine monohydrate, and stir at a constant temperature for 30min until completely dissolved. Step 3, complexation reaction: 75g g of glycine is added to the creatine solution at a rate of 10g / min. After the addition is completed, the stirring rate is increased to 280r / min, and the temperature is increased to 53℃ at a rate of 2.5℃ / min. The complexation reaction is maintained at this temperature for 2h. At the same time, the stirring is carried out in stages until the complexation reaction is complete. Step 4, gradient cooling: adopt step-by-step gradient cooling, first cool down to 28℃ at a rate of 5℃ / h, stir at a constant temperature of 200r / min for 1h, then cool down to 3℃ at a rate of 3℃ / h, and continue stirring at a speed of 180r / min. The total cooling process takes 20h. Step 5: Crystallization and ripening. Then, maintain a constant temperature of 3°C and stir at a low speed of 150 r / min for 2 hours. After that, let it stand for 10 minutes to allow the crystals to settle completely. Step 6: Filter, dry and sieve. After filtration, vacuum dry to obtain 190g of creatine glycinate, with a molar yield of 93% and a purity of 99.7%.

[0016] Example 3 A method for preparing creatine glycine salt includes the following steps: Step 1, Pretreatment: Dry 150g of creatine monohydrate at 45℃ until the moisture content is 0.3%, pass it through an 80-mesh sieve, and pass 75g of glycine through a 100-mesh sieve. Place them in a desiccator for later use. Meanwhile, ethanol is selected as the reaction solvent. Step 2: Dissolve the raw materials. Add 600g of ethanol to the reaction vessel, start stirring at 250r / min, heat to 50℃, add creatine monohydrate, and stir at a constant temperature for 30min until completely dissolved. Step 3, complexation reaction: 75g g of glycine is added to the creatine solution at a rate of 10g / min. After the addition is completed, the stirring rate is increased to 300r / min, and the temperature is increased to 55℃ at a rate of 3℃ / min. The complexation reaction is maintained at this temperature for 2h. At the same time, the stirring is carried out in stages until the complexation reaction is complete. Step 4, gradient cooling: adopt step-by-step gradient cooling, first cool down to 30℃ at a rate of 5℃ / h, stir at a constant temperature of 200r / min for 1h, then cool down to 5℃ at a rate of 3℃ / h, and continue stirring at a constant temperature of 200r / min. The total cooling process takes 22h. Step 5: Crystallization and ripening. Then, maintain a constant temperature of 5°C and stir at a low speed of 150 r / min for 2 hours. After that, let it stand for 10 minutes to allow the crystals to settle completely. Step 6: Filter, dry and sieve. After filtration, vacuum dry to obtain 188g of creatine glycinate, with a molar yield of 92% and a purity of 99.8%.

[0017] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. A method for preparing creatine glycine salt, characterized in that: Includes the following steps: Step 1, Pretreatment: Dry creatine monohydrate at 40~45℃ until the moisture content is ≤0.5%, pass it through an 80-mesh sieve, and glycine through a 100-mesh sieve. Place them in a desiccator for later use. At the same time, select a reaction solvent and the solid-liquid mass ratio of creatine monohydrate to the reaction solvent is 1:

4. Step 2: Dissolve the raw materials. Add the reaction solvent to the reaction vessel, start stirring at 200-250 r / min, heat to 45-50℃, add creatine monohydrate, and stir at a constant temperature for 30 min until completely dissolved to obtain a creatine solution. Step 3, complexation reaction: add pretreated glycine to the creatine solution. The mass ratio of creatine monohydrate to glycine is 2:

1. After the addition is completed, increase the stirring speed to 250~300 r / min and heat up. Keep the complexation reaction at this temperature for 2 hours. Stir in stages until the complexation reaction is complete. Step 4: Gradual cooling. After the reaction is complete, a gradient cooling process is adopted, with a total cooling time of 18-22 hours. Step 5: Crystallization and ripening, then maintain a constant temperature of 0~5℃ and stir at a low speed of 150r / min for 2 hours, then let stand for 10 minutes to allow the crystals to settle completely. Step 6: Filter, dry and sieve. After filtration, vacuum dry to finally obtain creatine glycine salt.

2. The method for preparing creatine glycine salt according to claim 1, characterized in that: The reaction solution in step 1 is one or more of water, methanol, and ethanol mixed in proportion.

3. The method for preparing creatine glycine salt according to claim 1, characterized in that: In step 3, after the material is added, the temperature is increased to 50-55℃ at a rate of 2-3℃ / min.

4. The method for preparing creatine glycine salt according to claim 1, characterized in that: In step 3, the stirring is carried out in stages: the stirring rate is 300 r / min for the first hour and 250 r / min for the second hour.

5. The method for preparing creatine glycine salt according to claim 1, characterized in that: In step 4, the gradient cooling is as follows: first, the temperature is lowered to 25~30℃ at a rate of 5℃ / h, and then stirred at a constant temperature of 200r / min for 1h. Then, the temperature is lowered to 0~5℃ at a rate of 3℃ / h, and stirred continuously at a speed of 150~200r / min.

6. A creatine glycine salt, characterized in that: It is prepared by the preparation method described in any one of claims 1-5.

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