Preparation method of creatine monohydrate

Abstract

The invention relates to a creatine monohydrate preparation method, which comprises: S1, carrying out a first reaction on a methylaminoacetonitrile aqueous solution and a first sodium hydroxide aqueous solution to obtain a sodium sarcosinate-containing aqueous solution; s2, carrying out separation treatment on the aqueous solution containing sodium sarcosine in the step S1 by adopting a bipolar membrane electrodialysis device to obtain an aqueous solution containing sarcosine and a second sodium hydroxide solution; and S3, carrying out a second reaction on the aqueous solution containing sarcosine in the step S2 and cyanamide to obtain a crude product containing sarcosine monohydrate. The creatine monohydrate prepared by the preparation method provided by the invention is high in purity and does not contain dicyandiamide and creatinine impurities, and the total yield of the creatine monohydrate is 90% or above.

Description

Technical Field

[0001] The present application relates to a method for preparing creatine monohydrate. Background Art

[0002] Creatine monohydrate is a pharmaceutical raw material and health product additive that can inhibit the generation of muscle fatigue factors, reduce fatigue and tension, restore physical fitness, and accelerate human protein synthesis, making muscles stronger and enhancing muscle elasticity. In addition, creatine monohydrate can also lower cholesterol, blood lipids and blood sugar levels, improve muscle atrophy in middle-aged and elderly people, and delay aging.

[0003] The existing creatine preparation technologies mainly include the following categories:

[0004] 1) Preparation of creatine by reaction of cyanamide with sarcosine (Ullmann's Chemical Industry Encyclopedia, 5th edition, volume A12, page 552, VCH Verlagsgesellschaft, Weinheim (1987));

[0005] 2) preparing creatine by reacting cyanamide with an aqueous solution of sodium sarcosinate or potassium sarcosinate (as disclosed in CN1253945A and CN101434563A);

[0006] 3) S-methylisothiourea reacts with an aqueous solution of sodium sarcosinate or potassium sarcosinate to prepare creatine (as disclosed in US6326513B1 and CN1287118A);

[0007] 4) Using chloroacetic acid as a raw material, reacting with an aqueous solution of methylamine and an aqueous solution of cyanamide in sequence to prepare creatine (as disclosed in CN1240207A);

[0008] 5) N-methylguanidinoethanol is reacted with dehydrogenase to prepare creatine (as disclosed in CN102584636A and CN101415672A).

[0009] The process of preparing creatine with chloroacetic acid, methylamine and cyanamide uses a molar ratio of chloroacetic acid to methylamine of 1:8 to 1:12. A large amount of methylamine hydrochloride is produced in the reaction, which brings difficulties to the subsequent purification of the product. In addition, the product produced by this method has a bitter taste and needs to be treated with a debittering agent such as sodium thiosulfate. The post-treatment process is complicated and the yield is only about 50%. S-methylisothiourea reacts with sodium sarcosinate or potassium sarcosinate aqueous solution to prepare creatine. This process produces methyl mercaptan byproducts, which have an unpleasant smell and are neurotoxic. The tail gas can only be completely absorbed by alkali solution, which easily causes air pollution. It also affects the taste of creatine. The reaction of cyanamide with sodium sarcosinate or potassium sarcosinate aqueous solution to prepare creatine is the main method for producing creatine in China. The existing processes all use inorganic acids such as hydrochloric acid or organic acids such as acetic acid to adjust the pH value of the reaction solution of cyanamide and sodium sarcosinate. After heating the reaction for a certain period of time, it is cooled, crystallized, and filtered to obtain crystals. The crystals are washed with deionized water several times and dried to obtain a monohydrate creatine product. However, the creatine monohydrate obtained by this process has low purity, large salt residues, large dicyandiamide residues from the polymerization of monocyanamide, and much impurity creatine residues. Summary of the invention

[0010] In order to solve the above technical problems existing in the prior art, the present application provides a method for preparing creatine monohydrate. The creatine monohydrate prepared by the preparation method provided in the present application has high purity, does not contain dicyandiamide and creatinine impurities, and the overall yield of creatine monohydrate is above 90%.

[0011] The preparation method of creatine monohydrate provided in the present application comprises the following steps:

[0012] S1: allowing the methylaminoacetonitrile aqueous solution and the first sodium hydroxide aqueous solution to undergo a first reaction to obtain an aqueous solution containing sodium sarcosinate;

[0013] S2: using a bipolar membrane electrodialysis device to separate the aqueous solution containing sodium sarcosinate in step S1 to obtain an aqueous solution containing sarcosine and a second sodium hydroxide solution;

[0014] S3: subjecting the aqueous solution containing sarcosine in step S2 to a second reaction with cyanamide to obtain a crude product containing sarcosine monohydrate.

[0015] The preparation method provided by the application comprises the following steps: sodium sarcosinate is separated by a bipolar membrane to obtain sarcosine and a sodium hydroxide aqueous solution; the creatine monohydrate product obtained by direct reaction of sarcosine has better product quality; the obtained 8%-10% sodium hydroxide aqueous solution can be used in the previous step after the concentration is increased, and can also be used in the production of other products without affecting the overall product yield; the overall yield of creatine monohydrate is above 90%.

[0016] In some embodiments, the preparation method further comprises step S4: separating and drying the crude product of step S3 to obtain creatine monohydrate.

[0017] In some embodiments, in step S2, in the bipolar membrane electrodialysis device, the flow rate of the aqueous solution (feed liquid) containing sodium sarcosinate is 3 cm / s-25 cm / s, for example, 4 cm / s, 5 cm / s, 6 cm / s, 7 cm / s, 8 cm / s, 9 cm / s, 10 cm / s, 11 cm / s, 12 cm / s, 13 cm / s, 14 cm / s, 15 cm / s, 16 cm / s, 17 cm / s, 18 cm / s, 19 cm / s, 20 cm / s, 21 cm / s, 23 cm / s or any value therebetween. In some embodiments, the flow rate of the aqueous solution containing sodium sarcosinate is 5 cm / s-20 cm / s. In some embodiments, the flow rate of the aqueous solution containing sodium sarcosinate is 10 cm / s-13 cm / s.

[0018] In some embodiments, in the bipolar membrane electrodialysis device, the temperature of the separation process is 5°C-70°C, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or any value therebetween. In some embodiments, the temperature of the separation process is 10°C-60°C. In some embodiments, the temperature of the separation process is 20°C-30°C.

[0019] In some embodiments, the current of the bipolar membrane electrodialysis device is 1A-10A, such as 2A, 3A, 4A, 5A, 6A, 7A, 8A, 9A or any value therebetween. In some embodiments, the operating current of the bipolar membrane electrodialysis device is 5A-7A.

[0020] In some embodiments, the separation process is stopped when the conductivity of the material chamber drops to 100us / cm-500us / cm, for example, 150us / cm, 200us / cm, 250us / cm, 300us / cm, 350us / cm, 400us / cm or 450us / cm.

[0021] In some embodiments, the feed solution obtained in the acid chamber of the bipolar membrane electrodialysis device is a sarcosine aqueous solution, and the feed solution obtained in the alkali chamber is a second sodium hydroxide solution (8-10% sodium hydroxide solution).

[0022] In some embodiments, in step S1, the mass concentration of the first sodium hydroxide aqueous solution is 45%-50%, for example, 46%, 47%, 48% or 49%.

[0023] In some embodiments, the mass concentration of the second sodium hydroxide solution in step S2 is 8%-10%, for example 8.5%, 9% or 9.5%. In some embodiments, the mass concentration of the second sodium hydroxide solution is adjusted to 45%-50% and then circulated to step S1.

[0024] In some embodiments, in step S1, the mass ratio of methylaminoacetonitrile to sodium hydroxide is (1-2):1, for example, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or any value therebetween. In some embodiments, in step S1, the mass ratio of methylaminoacetonitrile to sodium hydroxide is (1-1.5):1.

[0025] In some embodiments, in step S1, the temperature of the first reaction is greater than or equal to 60° C., for example, 65° C., 70° C., 75° C., 80° C., 85° C., 90° C. or 95° C. In some embodiments, in step S1, the temperature of the first reaction is 60° C.-90° C.

[0026] In some embodiments, in step S1, the first reaction time is 1 h-10 h, for example, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h or 9 h. In some embodiments, in step S1, the first reaction time is 3 h-8 h.

[0027] In some embodiments, in step S1, the first reaction includes: adding an aqueous solution of methylaminoacetonitrile to a first sodium hydroxide solution, wherein the temperature of the first sodium hydroxide solution is 60°C-65°C, absorbing the generated ammonia during the addition process, and after the addition is completed, heating the reaction solution to 90°C-95°C, keeping the temperature and condensing, removing the ammonia, and obtaining an aqueous solution containing sodium sarcosinate.

[0028] In some embodiments, in step S1, the preparation of the methylaminoacetonitrile aqueous solution comprises:

[0029] (a) cooling the formaldehyde solution to 5°C-8°C and adjusting the pH to 7.5-8.2, adding hydrocyanic acid, controlling the temperature of the reaction system to 10°C-18°C during the addition process, and controlling the temperature of the reaction system to 15°C-18°C after the addition is completed, keeping the temperature to react and obtaining hydroxyacetonitrile, and then adjusting the pH to 1.5-2.0;

[0030] (b) adding the material obtained in step (a) to a methylamine aqueous solution, wherein the temperature of the methylamine aqueous solution is 5°C-11°C, and the temperature of the reaction system is controlled to be 12°C-18°C during the addition process, and the temperature of the reaction system is controlled to be 15°C-18°C after the addition is completed, and the reaction is kept warm to obtain an aqueous solution containing methylaminoacetonitrile.

[0031] In some embodiments, the mass concentration of the formaldehyde solution is 35%-40%, such as 36%, 37%, 38% or 39%. In some embodiments, the mass concentration of the methylamine aqueous solution is 38%-45%, such as 39%, 40%, 41%, 42%, 43% or 44%.

[0032] In some embodiments, the concentration of the hydrocyanic acid is 95%-99%, such as 96%, 97% or 98%. In some embodiments, the molar ratio of hydrogen cyanide in the hydrocyanic acid to formaldehyde in the formaldehyde solution is (1-1.1):1.

[0033] In some embodiments, the molar ratio of methylamine in the methylamine aqueous solution to formaldehyde in the formaldehyde solution is (1.01-1.05):1, for example, 1.02:1, 1.03:1 or 1.04:1.

[0034] In some embodiments, in step S3, the temperature of the second reaction is 50° C.-80° C., for example, 60° C., 65° C., 70° C. or 75° C. In some embodiments, in step S3, the temperature of the second reaction is 65° C.-70° C.

[0035] In some embodiments, in step S3, the second reaction time is 5h-20h, for example, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h or 19h. In some embodiments, in step S3, the second reaction time is 10h-15h.

[0036] In some embodiments, in step S3, the molar ratio of sodium sarcosine to cyanamide is 1:(0.9-1.1). In some embodiments, in step S3, the molar ratio of sodium sarcosine to cyanamide is 1:(1-1.05).

[0037] In some embodiments, in step S3, the second reaction includes: adjusting the pH of the aqueous solution containing sarcosine to 8.5-9.0 and then heating it to 65-70°C, adding cyanamide dropwise, and controlling the temperature to be 65-70°C. After the addition is completed, the reaction solution is cooled to 20°C-30°C and separated to obtain a crude product containing sarcosine monohydrate.

[0038] In some embodiments, in step S4, the crude product containing creatine monohydrate is mixed with water, heated to 80°C-90°C to dissolve, and then cooled to 10°C-15°C for separation and drying to obtain creatine monohydrate.

[0039] In some embodiments, the cooling rate is 2°C / h-8°C / h, for example, 3°C / h, 4°C / h, 5°C / h, 6°C / h or 7°C / h. In some embodiments, the cooling rate is 4°C / h-6°C / h.

[0040] In some embodiments, the method for preparing creatine monohydrate comprises the following steps:

[0041] 1) reacting a formaldehyde solution with hydrocyanic acid to obtain a solution containing hydroxyacetonitrile;

[0042] 2) reacting the solution containing hydroxyacetonitrile in step 1) with an aqueous solution of methylamine to obtain an aqueous solution containing methylaminoacetonitrile;

[0043] 3) allowing the aqueous solution of methylaminoacetonitrile in step 2) and the first aqueous solution of sodium hydroxide to undergo a first reaction to obtain an aqueous solution containing sodium sarcosinate;

[0044] 4) using a bipolar membrane electrodialysis device to separate the aqueous solution containing sodium sarcosinate in step 3) to obtain an aqueous solution containing sarcosine and a second sodium hydroxide solution;

[0045] 5) subjecting the aqueous solution containing sarcosine in step 4) to a second reaction with cyanamide to obtain a crude product containing sarcosine monohydrate;

[0046] 6) separating and drying the crude product of step 5) to obtain creatine monohydrate;

[0047] In some embodiments, the method for preparing creatine monohydrate comprises the following steps:

[0048] (a) cooling the formaldehyde solution to 5°C-8°C and adjusting the pH to 7.5-8.2, adding hydrocyanic acid, controlling the temperature of the reaction system to 10°C-18°C during the addition process, and controlling the temperature of the reaction system to 15°C-18°C after the addition is completed, keeping the temperature to react and obtaining hydroxyacetonitrile, and then adjusting the pH to 1.5-2.0;

[0049] (b) adding the material obtained in step (a) to a methylamine aqueous solution, wherein the temperature of the methylamine aqueous solution is 5°C-11°C, the temperature of the reaction system is controlled to be 12°C-18°C during the addition process, and the temperature of the reaction system is controlled to be 15°C-18°C after the addition is completed, and the reaction is kept warm to obtain an aqueous solution containing methylaminoacetonitrile;

[0050] (c) adding the aqueous solution of methylaminoacetonitrile obtained in step (b) to a first sodium hydroxide solution, wherein the temperature of the first sodium hydroxide solution is 60° C.-65° C., absorbing the generated ammonia during the addition process, and heating the reaction solution to 90° C.-95° C. after the addition is completed, keeping the temperature and condensing, removing the ammonia, and obtaining an aqueous solution containing sodium sarcosinate;

[0051] (d) separating the aqueous solution containing sodium sarcosinate in step (c) by a bipolar membrane electrodialysis device to obtain an aqueous solution containing sarcosine and a second sodium hydroxide solution, wherein the second sodium hydroxide aqueous solution is added with solid sodium hydroxide to adjust the content to 45-50% and then circulated to step (c);

[0052] (e) adjusting the pH of the aqueous solution containing sarcosine obtained in step (d) to 8.5-9.0 and then heating it to 65-70° C., adding cyanamide dropwise at 65-70° C., and after the addition is completed, cooling the reaction solution to 20° C.-30° C. and separating to obtain a crude product containing sarcosine monohydrate;

[0053] (f) mixing the crude product containing creatine monohydrate obtained in step (e) with water, heating the mixture to 80° C.-90° C. to dissolve the mixture, and then cooling the mixture to 10° C.-15° C. to separate and dry the mixture to obtain creatine monohydrate.

[0054] In some embodiments, the preparation method of creatine monohydrate provided in the present application comprises the following specific steps:

[0055] (1) Add 37% formaldehyde to the reactor, start stirring and lower the material temperature to 5-8°C, add liquid alkali to adjust the pH to 7.5-8.2, then start to drop hydrocyanic acid, control the temperature at 10-18°C during the dropwise addition, and complete the dropwise addition in about 2 hours. After the dropwise addition is completed, control the temperature at 15-18°C to keep the reaction for 0.5 hour to obtain hydroxyacetonitrile. After the insulation is completed, add 50% sulfuric acid to adjust the pH to 1.5-2.0 for standby use.

[0056] (2) Add 40% methylamine aqueous solution to the reactor, start stirring and cool to 10°C, then slowly drip the material from step (1) into the methylamine solution, control the temperature to be 12-18°C during the dripping process, and complete the dripping in about 2 hours. After the dripping is completed, control the temperature to be 15-18°C and keep the reaction for 1 hour to obtain methylaminoacetonitrile.

[0057] (3) After obtaining methylaminoacetonitrile, add sodium hydroxide solution to the reactor, start stirring and heat to 60°C, then slowly drip the material into the sodium hydroxide solution. During the dripping process, pay attention to the absorption of ammonia and control the material to prevent it from rushing. After the dripping is completed, heat to above 90°C, continue to keep warm and condense for 2 hours to drive out the excess ammonia, and obtain sodium sarcosine, and detect the content.

[0058] (3) The sodium sarcosinate aqueous solution obtained by the reaction is fed into a bipolar membrane electrodialysis device to separate and remove part of the sodium ions therein, thereby obtaining a sarcosine aqueous solution and a sodium hydroxide aqueous solution. The sodium hydroxide aqueous solution is added with solid sodium hydroxide to adjust the content to 45-50% before use.

[0059] (4) Adjust the pH of the sarcosine aqueous solution to 8.5-9.0 and then heat it to 65-70°C, and slowly add 30% cyanamide, controlling the temperature to add at 65-70°C for 10-14 hours. After the addition is completed, the reaction solution is cooled to 30°C, and hydrochloric acid is added to adjust the pH to 7.5-8.0. The material is cooled to 15-25°C and separated to obtain a wet creatine product. The wet product is dried to obtain qualified creatine monohydrate.

[0060] The beneficial effects of this application are:

[0061] (1) The creatine monohydrate prepared by the preparation method provided in the present application has high purity, does not contain dicyandiamide and creatinine impurities, and the overall yield of creatine monohydrate is above 90%.

[0062] (2) In the preparation method provided in the present application, sodium sarcosinate is separated by a bipolar membrane to obtain sarcosine and a sodium hydroxide aqueous solution. The creatine monohydrate product obtained by direct reaction of sarcosine has better quality. The obtained 8-10% sodium hydroxide aqueous solution can be used in the previous step after the concentration is increased, and can also be used in the production of other products without affecting the overall product yield. DETAILED DESCRIPTION

[0063] In order to make the purpose, technical solution and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the embodiments. The specific embodiments described here are only used to explain the present application and are not intended to constitute any limitation to the present application.

[0064] Unless otherwise specified, % in the following examples and comparative examples represents mass percentage.

[0065] Example 1

[0066] (1) Add 1860 g of 37% formaldehyde to the reactor, start stirring, start chilled brine, lower the material temperature to 5°C, add 50% liquid caustic soda to adjust the pH to 7.9. After the addition is completed, stir for about 2-4 minutes, and then start dripping 650 g of liquid hydrocyanic acid, which is dripped in about 2 hours. During the dripping process, keep the material temperature between 10°C and 18°C. After the dripping is completed, keep it warm at 15°C and 18°C ​​for 30 minutes. After the insulation is completed, adjust the pH value to 1.5-2 with 50% sulfuric acid to obtain a synthetic liquid for use.

[0067] (2) Add 1778g of 40% methylamine into the synthesis reactor, cool to about 10°C, and then slowly dropwise add the first step synthesis solution, and complete the dropwise addition within 1.5 hours. During the dropwise addition, maintain the temperature at 12°C-18°C. After the dropwise addition is completed, keep the temperature at about 15°C-18°C for 1 hour and discharge the material to obtain 4288g of 37% methylaminoacetonitrile.

[0068] (3) After adding 3058g of 30% liquid caustic soda to the hydrolysis reactor, the temperature was raised to 60°C and the above-mentioned methylaminoacetonitrile was added dropwise, wherein the mass ratio of methylaminoacetonitrile to sodium hydroxide in the liquid caustic soda was 1.18:1, and ammonia was absorbed by a tail gas device, and the addition was completed after about 3 hours. After the addition was completed, the temperature was raised to 90°C and condensed and kept warm for 2 hours to obtain 6580g of sodium sarcosine aqueous solution, and the sodium sarcosine content was measured to be 36.5%.

[0069] The prepared sodium sarcosinate aqueous solution is passed into a bipolar membrane electrodialysis device to separate and remove part of the Na ions therein, thereby obtaining a sarcosine aqueous solution and a sodium hydroxide aqueous solution with a mass fraction of 8% to 10%.

[0070] The working current of the bipolar membrane electrodialysis device is 6A, the flow rate of the sodium sarcosinate aqueous solution is 12cm / s, and the separation temperature is 25°C. When the conductivity of the material chamber drops to 200us / cm, the operation is stopped, and the material solution obtained in the acid chamber is a sarcosine aqueous solution, and the material solution obtained in the alkali chamber is an 8-10% sodium hydroxide solution.

[0071] (4) The pH of the sarcosine aqueous solution obtained above was adjusted to 8.5-9.0 and then the temperature was raised. After the temperature was raised to 65-70°C, 500 g of 30% cyanamide was added dropwise, and the temperature was controlled to be 65-70°C. The addition was completed after about 12 hours. After the addition was completed, the temperature was lowered and separated after the temperature was lowered to 20-25°C to obtain 3133 g of wet creatine.

[0072] (5) 3133 g of wet creatine was added with 3472 g of pure water, and the temperature was raised to 80°C-90°C for dissolution, and then the temperature was lowered by 5°C per hour. After the temperature dropped to 10°C-15°C, the product was separated and dried to obtain 2901 g of creatine monohydrate, with a yield of 90.1%. The purity of the creatine monohydrate product was 99.9% as determined by liquid chromatography.

[0073] Example 2

[0074] The only difference from Example 1 is that the flow rate of the sodium sarcosinate aqueous solution in the bipolar membrane electrodialysis device is 3 cm / s. The yield of the creatine monohydrate product finally obtained is 86.3% and the purity is 98.6%.

[0075] Example 3

[0076] The only difference from Example 1 is that the flow rate of the sodium sarcosinate aqueous solution in the bipolar membrane electrodialysis device is 5 cm / s. The yield of the final creatine monohydrate product is 88.6% and the purity is 99.1%.

[0077] Example 4

[0078] The only difference from Example 1 is that the flow rate of the sodium sarcosinate aqueous solution in the bipolar membrane electrodialysis device is 20 cm / s. The yield of the creatine monohydrate product finally obtained is 83.5% and the purity is 97.6%.

[0079] Example 5

[0080] The only difference from Example 1 is that the flow rate of the sodium sarcosinate aqueous solution in the bipolar membrane electrodialysis device is 25 cm / s. The yield of the creatine monohydrate product finally obtained is 78.3% and the purity is 95.9%.

[0081] Example 6

[0082] The only difference from Example 1 is that the separation temperature in the bipolar membrane electrodialysis device is 5° C. The yield of the creatine monohydrate product finally obtained is 83.2% and the purity is 97.3%.

[0083] Example 7

[0084] The only difference from Example 1 is that the separation temperature in the bipolar membrane electrodialysis device is 20° C. The yield of the creatine monohydrate product finally obtained is 90.6% and the purity is 100.1%.

[0085] Example 8

[0086] The only difference from Example 1 is that the separation temperature in the bipolar membrane electrodialysis device is 60° C. The yield of the creatine monohydrate product finally obtained is 90.1% and the purity is 99.9%.

[0087] Example 9

[0088] The only difference from Example 1 is that the separation temperature in the bipolar membrane electrodialysis device is 70° C. The yield of the creatine monohydrate product finally obtained is 85.3% and the purity is 98.3%.

[0089] The technical solution of the present application is not limited to the above-mentioned specific embodiments, and all technical variations made according to the technical solution of the present application fall within the protection scope of the present application.

Claims

1. A method for preparing creatine monohydrate, comprising the following steps: S1: allowing the methylaminoacetonitrile aqueous solution and the first sodium hydroxide aqueous solution to undergo a first reaction to obtain an aqueous solution containing sodium sarcosinate; S2: using a bipolar membrane electrodialysis device to separate the aqueous solution containing sodium sarcosinate in step S1 to obtain an aqueous solution containing sarcosine and a second sodium hydroxide solution; S3: subjecting the aqueous solution containing sarcosine in step S2 to a second reaction with cyanamide to obtain a crude product containing sarcosine monohydrate.

2. The preparation method according to claim 1, characterized in that: The method further comprises step S4: separating and drying the crude product of step S3 to obtain creatine monohydrate.

3. The preparation method according to claim 1 or 2, characterized in that: In step S2, in the bipolar membrane electrodialysis device, the flow rate of the aqueous solution containing sodium sarcosinate is 3 cm / s-25 cm / s, preferably 5 cm / s-20 cm / s, more preferably 10 cm / s-13 cm / s; and / or The temperature for separation treatment is 5°C-70°C, preferably 10°C-60°C, and preferably 20°C-30°C.

4. The preparation method according to any one of claims 1 to 3, characterized in that In step S2, the operating current of the bipolar membrane electrodialysis device is 1A-10A, preferably 5A-7A; and / or When the conductivity of the material chamber drops to 100us / cm-500us / cm, preferably to 150-250us / cm, the separation process is stopped.

5. The preparation method according to any one of claims 1 to 4, characterized in that: In step S1, the mass concentration of the first sodium hydroxide aqueous solution is 45%-50%; The mass concentration of the second sodium hydroxide solution in step S2 is 8%-10%. Preferably, the mass concentration of the second sodium hydroxide solution is adjusted to 45%-50% and then circulated to step S1.

6. The preparation method according to any one of claims 1 to 5, characterized in that: In step S1, the mass ratio of methylaminoacetonitrile to sodium hydroxide is (1-2):1, preferably (1-1.5):1; The temperature of the first reaction is greater than or equal to 60°C, preferably 60°C-90°C; The first reaction time is 1h-10h, preferably 3h-8h; Preferably, the first reaction comprises: adding an aqueous solution of methylaminoacetonitrile to a first sodium hydroxide solution, wherein the temperature of the first sodium hydroxide solution is 60°C-65°C, absorbing the generated ammonia during the adding process, and after the adding is completed, heating the reaction solution to 90°C-95°C, keeping the temperature and condensing, removing the ammonia, and obtaining an aqueous solution containing sodium sarcosinate.

7. The preparation method according to any one of claims 1 to 6, characterized in that: In step S1, the preparation of the methylaminoacetonitrile aqueous solution comprises: (a) cooling the formaldehyde solution to 5°C-8°C and adjusting the pH to 7.5-8.2, adding hydrocyanic acid, controlling the temperature of the reaction system to 10°C-18°C during the addition process, and controlling the temperature of the reaction system to 15°C-18°C after the addition is completed, keeping the temperature to react and obtaining hydroxyacetonitrile, and then adjusting the pH to 1.5-2.0; (b) adding the material obtained in step (a) to a methylamine aqueous solution, wherein the temperature of the methylamine aqueous solution is 5°C-11°C, the temperature of the reaction system is controlled to be 12°C-18°C during the addition process, and the temperature of the reaction system is controlled to be 15°C-18°C after the addition is completed, and the reaction is kept warm to obtain an aqueous solution containing methylaminoacetonitrile, Preferably, the mass concentration of the formaldehyde solution is 35%-40%, and the mass concentration of the methylamine aqueous solution is 38-45%; Preferably, the concentration of the hydrocyanic acid is 95%-99%, and the molar ratio of hydrogen cyanide in the hydrocyanic acid to formaldehyde in the formaldehyde solution is (1-1.1):1; Preferably, the molar ratio of methylamine in the methylamine aqueous solution to formaldehyde in the formaldehyde solution is (1.01-1.05):

1.

8. The preparation method according to any one of claims 1 to 7, characterized in that: In step S3, the temperature of the second reaction is 50°C-80°C, preferably 65°C-70°C, and the time of the second reaction is 5h-20h, preferably 10h-15h; and / or The molar ratio of sodium sarcosine to cyanamide is 1:(0.9-1.1), preferably 1:(1-1.05).

9. The preparation method according to any one of claims 1 to 8, characterized in that: In step S3, the second reaction comprises: adjusting the pH of the aqueous solution containing sarcosine to 8.5-9.0 and then heating it to 65-70° C., adding cyanamide dropwise, and controlling the temperature to be 65-70° C. After the addition is completed, cooling the reaction solution to 20° C.-30° C. and separating to obtain a crude product containing sarcosine monohydrate.

10. The preparation method according to any one of claims 2 to 9, characterized in that: In step S4, the crude product containing creatine monohydrate is mixed with water, heated to 80°C-90°C to dissolve, and then cooled to 10°C-15°C for separation and drying to obtain creatine monohydrate; Preferably, the cooling rate is 2°C / h-8°C / h, preferably 4°C / h-6°C / h.