Method for preparing high-content creatine monohydrate

Abstract

The invention provides a method for preparing high-content creatine monohydrate. The method comprises the following steps: continuously preparing a sarcosine aqueous solution from a sodium sarcosine aqueous solution through bipolar membrane electrodialysis, and then carrying out continuous scraper evaporation concentration to obtain a sarcosine concentrated solution; the method comprises the following steps: respectively introducing a sarcosine concentrated solution, a cyanamide (IV) aqueous solution and an additive into a continuous kettle, carrying out guanidination reaction, and then carrying out cooling crystallization, centrifugation, washing and drying to obtain creatine monohydrate; the additive is one or a combination of more than two of sodium decyl sulfate, sodium dodecyl sulfate, sodium hexadecyl sulfate, sodium octadecyl sulfate or sodium octadecyl sulfonate. The method has the advantages of high automation degree, simple operation, easy realization and control of reaction conditions, low energy consumption, low cost, avoidance of generation of sodium chloride waste salt, safety and environmental protection; the obtained creatine monohydrate has the advantages of high yield, high purity, uniform particles, good fluidity and difficulty in caking.

Description

Technical Field

[0001] The invention relates to a method for preparing high-content creatine monohydrate, belonging to the technical field of synthesis of health products. Background Art

[0002] Creatine, also known as myostatin, has the structural formula shown in Formula I below. It is a naturally occurring amino acid derivative in the human body that can rapidly increase muscle strength, promote new muscle growth, accelerate fatigue recovery, and enhance explosive power. Creatine monohydrate, a type of creatine, is widely used in foods, beverages, and additives, and can be used as a pharmaceutical raw material and health supplement additive. It can inhibit the occurrence of muscle fatigue, reduce fatigue and tension, restore physical fitness, accelerate protein synthesis, strengthen muscles, enhance muscle elasticity, lower cholesterol, blood lipids, and blood sugar levels, and improve muscle atrophy in middle-aged and elderly people, delaying aging.

[0003]

[0004] There are several existing methods for synthesizing creatine monohydrate, including: 1. Reaction of sodium sarcosinate with an aqueous cyanamide solution, with the pH of the reaction solution continuously adjusted to 9-10 with hydrochloric acid to produce creatine monohydrate; 2. Reaction of an aqueous chloroacetic acid solution, an aqueous monomethylamine solution, and an aqueous cyanamide solution to produce creatine monohydrate; and 3. Reaction of S-methylisothiourea with an aqueous sodium or potassium sarcosinate solution to produce creatine. Each of these processes has various drawbacks.

[0005] In the prior art, process 1 is the main synthesis route, but it is produced by a batch process, which has a low degree of automation, cumbersome operation, high energy consumption, and difficult to control reaction conditions. Impurities such as dicyandiamide and creatinine are easily generated (the impurity structural formula is shown below). The obtained creatine monohydrate has low purity and low yield. In addition, hydrochloric acid is often used to neutralize sodium sarcosinate, generating a large amount of difficult-to-handle sodium chloride waste salt. In addition, the product particles are uneven, have poor fluidity, and are prone to agglomeration.

[0006]

[0007] Therefore, it is an urgent technical problem to find a method for preparing creatine monohydrate with high degree of automation, simple operation, easy to implement and control reaction conditions, few impurities, high yield, high purity, uniform product particles, good fluidity, not easy to agglomerate, low energy consumption, low cost, safety and environmental protection. Summary of the Invention

[0008] In response to the shortcomings of the prior art, the present invention provides a method for preparing high-content creatine monohydrate. The method has a high degree of automation, simple operation, easy-to-implement and controllable reaction conditions, low energy consumption, low cost, avoids the generation of sodium chloride waste salt, and is safe and environmentally friendly. The resulting creatine monohydrate has the advantages of high yield, high purity, uniform particles, good fluidity, and resistance to agglomeration.

[0009] The technical solutions of the present invention are as follows:

[0010] A method for preparing high-content creatine monohydrate comprises the steps of:

[0011] (1) Sodium sarcosinate (II) aqueous solution is subjected to bipolar membrane electrodialysis to continuously prepare sarcosine (III) aqueous solution, which is then concentrated by continuous scraper distillation to obtain sarcosine (III) concentrated solution;

[0012]

[0013] (2) introducing the concentrated solution of sarcosine (III), the aqueous solution of monocyanamide (IV), and the additive into a continuous reactor, respectively, undergoing guanidation reaction, followed by cooling crystallization, centrifugation, washing, and drying to obtain creatine monohydrate (I);

[0014] The additive is one or a combination of two or more of sodium decyl sulfate, sodium dodecyl sulfate, sodium hexadecyl sulfate, sodium octadecyl sulfate or sodium octadecyl sulfonate;

[0015]

[0016] According to the preferred embodiment of the present invention, in step (1), the mass concentration of the sodium sarcosinate aqueous solution is 10-50%, preferably 20-40%.

[0017] Preferably, according to the present invention, in step (1), the pH of the sarcosine (III) aqueous solution is 9-11.

[0018] Preferably, according to the present invention, in step (1), the sarcosine (III) aqueous solution continuously prepared by bipolar membrane electrodialysis continuously enters a heat exchanger for heat exchange, and then undergoes continuous scraper distillation and concentration; during the heat exchange, the scraper vaporized water serves as a heat medium, and the sarcosine aqueous solution serves as a coolant. The scraper vaporized water exchanges heat with the sarcosine aqueous solution, the scraper vaporized water condenses, and the sarcosine aqueous solution is heated to 10-15°C.

[0019] According to the preferred embodiment of the present invention, in step (1), the concentration temperature is 40 to 100°C, preferably 60 to 80°C.

[0020] According to the preferred embodiment of the present invention, in step (1), the mass concentration of the sarcosine (III) concentrated solution is 20-55%, preferably 30-50%.

[0021] Preferably, according to the present invention, in step (1), a sodium hydroxide aqueous solution with a mass concentration of 10-32% or a hydrochloric acid aqueous solution with a mass concentration of 10%-38% is used to adjust the pH of the sarcosine (III) concentrate to 8-10.

[0022] According to the present invention, in step (1), a sodium sarcosinate (II) aqueous solution is continuously passed through a bipolar membrane electrodialysis device to produce a sarcosine (III) aqueous solution through continuous bipolar membrane electrodialysis; the sarcosine aqueous solution is continuously passed through a heat exchanger for heat exchange; and then continuously passed through a scraper evaporator to be concentrated through continuous scraper distillation to obtain a sarcosine (III) concentrated solution, and the pH is adjusted. The bipolar membrane electrodialysis and scraper distillation can be performed according to existing methods.

[0023] According to the preferred embodiment of the present invention, in step (2), the mass concentration of the aqueous solution of cyanamide (IV) is 20-50%.

[0024] According to the preferred embodiment of the present invention, in step (2), the additive is introduced into the continuous reactor in the form of a solid or an aqueous solution of the additive with a mass concentration of 5 to 50%.

[0025] According to the present invention, preferably, in step (2), the continuous reactor is composed of 3 to 8 reactors connected in series, preferably 4 to 6 reactors; the first reactor is simultaneously introduced with a sarcosine (III) concentrate, a cyanamide (IV) aqueous solution and an additive; each of the other reactors is simultaneously introduced with the reaction liquid obtained in the previous reactor and a cyanamide (IV) aqueous solution; in the first reactor, the molar ratio of sarcosine (III), cyanamide (IV) and the additive is (0.95 to 1.30): 1 / n: (0.001 to 0.01), preferably (0.98 to 1.1): 1 / n: (0.0011 to 0.0013), and the molar ratio of sarcosine (III) introduced into the first reactor to cyanamide introduced into each of the other reactors is (0.95 to 1.30): 1 / n, preferably (0.98 to 1.1): 1 / n, wherein n is the number of reactors.

[0026] According to the preferred embodiment of the present invention, in step (2), the guanidination reaction temperature is 50-90° C., preferably 60-80° C.; and the total reaction residence time is 120-360 min, preferably 180-300 min.

[0027] According to the preferred embodiment of the present invention, in step (2), the crystallization temperature is 0 to 25°C, preferably 5 to 15°C.

[0028] The method of the present invention is described as the following reaction scheme:

[0029]

[0030] The technical features and beneficial effects of the present invention are as follows:

[0031] 1. The method of the present invention utilizes bipolar membrane electrodialysis to continuously prepare sarcosine, and then continuously distills and concentrates the sarcosine concentrate by scraping. No hydrochloric acid is used to neutralize sodium sarcosinate, thus avoiding the generation of a large amount of difficult-to-treat sodium chloride waste salt. The by-product sodium hydroxide is reused to prepare sodium sarcosinate, which is environmentally friendly. Continuous distillation and concentration achieves thermal coupling, reducing energy consumption and costs.

[0032] 2. The present invention adopts a continuous reactor and adds additives such as sodium decyl sulfate, sodium dodecyl sulfate, sodium hexadecyl sulfate, sodium octadecyl sulfate, and sodium octadecyl sulfonate, which can reduce the occurrence of side reactions, effectively inhibit the formation of by-products such as dicyandiamide and creatinine, and improve the purity and yield of the product. The properties of the obtained creatine crystals are significantly improved, and the product particles are uniform, have good fluidity, and are not easy to agglomerate.

[0033] 3. The method of the present invention utilizes bipolar membrane electrodialysis to continuously prepare sarcosine, which is then concentrated by continuous water distillation using a scraper to obtain a sarcosine concentrate. The method then utilizes a continuous reactor for continuous reaction and adds additives to synthesize creatine, thereby resolving the problems of low product content, high impurity content, low yield, high energy consumption, low automation, cumbersome operation, large wastewater volume, uneven product particles, poor fluidity, and easy agglomeration. The method of the present invention has a high degree of automation, simple operation, time and labor saving, can achieve precise temperature control, and the reaction conditions are easy to implement and control. It has low energy consumption, low cost, avoids the generation of sodium chloride waste salt, and is safe and environmentally friendly. It effectively suppresses side reactions such as dicyandiamide and creatinine during the reaction process, resulting in creatine monohydrate with low impurities, high purity, high yield, uniform particles, good fluidity, and low agglomeration.

[0034] 4. In the traditional batch production process, the yield of creatine monohydrate is generally about 70%. By optimizing the reaction conditions, the present invention can achieve a product content of more than 99%, less impurities, and a guanidinium yield of 86%, which greatly reduces costs and is more environmentally friendly. DETAILED DESCRIPTION

[0035] The present invention will be described in further detail below with reference to specific embodiments, but the protection scope of the present invention is not limited to the description herein.

[0036] Unless otherwise specified, all raw materials used in the following examples are commercially available products.

[0037] The "%" in the examples are all weight ratios, unless otherwise specified. The yields in the examples are all molar yields.

[0038] Example 1: Preparation of Creatine Monohydrate

[0039] 5000 g (18.02 mol) of a 40% sodium sarcosinate aqueous solution was continuously introduced into a bipolar membrane electrodialysis apparatus at a flow rate of 19.82 g / min to produce a sarcosine aqueous solution having a pH of 10. The sarcosine aqueous solution was then continuously introduced into a heat exchanger (scrapered vaporized water was used as a heat medium and the sarcosine aqueous solution was used as a coolant. The scraped vaporized water exchanged heat with the sarcosine aqueous solution, the scraped vaporized water was condensed, and the sarcosine aqueous solution was heated to 10-15° C.). The solution was then continuously introduced into a scraped evaporator and concentrated by scraped water distillation (at a concentration temperature of 75-80° C.) to obtain a sarcosine concentrate having a mass concentration of 44.99%. The pH of the sarcosine concentrate was adjusted to 9.0 using a 30% aqueous hydrochloric acid solution.

[0040] Four 1000mL reactors A, B, C, and D were connected in series to form a continuous reactor; hot water was introduced into the reactor jacket in advance and heated to 65-70°C. The sarcosine concentrate obtained above was continuously introduced into reactor A at a flow rate of 14.13g / min (0.071mol / min), and a 20% aqueous solution of sodium decyl sulfate as an additive was added at a flow rate of 0.12g / min (0.00009mol / min). At the same time, a 30% aqueous solution of monocyanamide was introduced at a flow rate of 2.50g / min (0.018mol / min) to carry out guanylation reaction in reactor A; the reaction solution obtained in reactor A was continuously introduced into reactor B at a flow rate of 16.75g / min, and at the same time, a 20% aqueous solution of sodium decyl sulfate as an additive was added at a flow rate of 0.12g / min (0.00009mol / min). A 30% aqueous cyanamide solution was introduced into kettle B at a flow rate of 19.25 g / min, while a 30% aqueous cyanamide solution was introduced at a flow rate of 2.50 g / min, also in kettle C for guanylation. The reaction solution from kettle C was continuously introduced into kettle D at a flow rate of 21.75 g / min, while a 30% aqueous cyanamide solution was introduced at a flow rate of 2.50 g / min, also in kettle D for guanylation. The total reaction residence time was 214.48 min. The reaction solution from kettle D was cooled to 10°C for crystallization, centrifuged, washed, and dried to obtain creatine monohydrate with a content of 99.8%, 20 ppm dicyandiamide, and 18 ppm creatinine, for a molar yield of 85.0%. The creatine particles were uniform, had good fluidity, and were not prone to agglomeration, meeting product quality requirements.

[0041] Example 2: Preparation of Creatine Monohydrate

[0042] 5714.9 g (18.02 mol) of a 35% sodium sarcosinate aqueous solution was continuously introduced into a bipolar membrane electrodialysis apparatus at a flow rate of 23.71 g / min to produce a sarcosine aqueous solution having a pH of 9.7. The sarcosine aqueous solution was then continuously introduced into a heat exchanger (scrapered vaporized water was used as a heat medium and the sarcosine aqueous solution was used as a coolant. The scraped vaporized water exchanged heat with the sarcosine aqueous solution, the scraped vaporized water condensed, and the sarcosine aqueous solution was heated to 10-15° C.). The solution was then continuously introduced into a scraped evaporator and concentrated by scraped water distillation (at a concentration temperature of 70-75° C.) to obtain a sarcosine concentrate having a mass concentration of 40.0%. The pH of the sarcosine concentrate was adjusted to 8.5 using a 20% aqueous hydrochloric acid solution.

[0043] Five 1000mL reactors A, B, C, D, and E were connected in series to form a continuous reactor; hot water was introduced into the reactor jacket in advance and heated to 65-70°C. The sarcosine concentrate obtained above was continuously introduced into reactor A at a flow rate of 16.63g / min (0.075mol / min), and a 20% aqueous solution of sodium decyl sulfate as an additive was added at a flow rate of 0.12g / min (0.00009mol / min). At the same time, a 40% aqueous solution of cyanamide was introduced at a flow rate of 1.57g / min (0.015mol / min) to carry out a guanylation reaction in reactor A; the reaction solution obtained in reactor A was continuously introduced into reactor B at a flow rate of 18.32g / min, and a 40% aqueous solution of cyanamide was introduced at a flow rate of 1.57g / min to carry out a guanylation reaction in reactor B; The resulting reaction liquid was continuously passed into kettle C at a flow rate of 19.89 g / min, while a 40% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.57 g / min, where a guanidation reaction occurred. The reaction liquid from kettle C was continuously passed into kettle D at a flow rate of 21.46 g / min, while a 40% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.57 g / min, where a guanidation reaction occurred. The reaction liquid from kettle D was continuously passed into kettle E at a flow rate of 23.03 g / min, while a 40% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.57 g / min, where a guanidation reaction occurred. The total reaction residence time was 284 min. The reaction liquid from kettle E was cooled to 5°C for crystallization, centrifuged, washed, and dried to obtain creatine monohydrate with a content of 99.9%, 18 ppm dicyandiamide, and 17 ppm creatinine, with a molar yield of 85.2%. The creatine particles were uniform, had good fluidity, and were not prone to agglomeration, meeting product quality requirements.

[0044] Example 3: Preparation of Creatine Monohydrate

[0045] The same steps and conditions were as in Example 2, except that a 20% by mass aqueous sodium lauryl sulfate solution was added to kettle A at a rate of 0.135 g / min (0.00009 mol / min). The other steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, having a content of 99.9%, 5 ppm of dicyandiamide, and 6 ppm of creatinine, with a molar yield of 86.0%. The creatine particles were uniform, had good fluidity, were not prone to agglomeration, and met the product quality requirements.

[0046] Example 4: Preparation of Creatine Monohydrate

[0047] The same steps and conditions were as in Example 2, except that a 20% by mass aqueous sodium cetyl sulfate solution was added to kettle A at a rate of 0.16 g / min (0.00009 mol / min). The other steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, with a content of 99.8%, 10 ppm of dicyandiamide, and 12 ppm of creatinine, and a molar yield of 85.7%. The creatine particles were uniform, had good fluidity, were not prone to agglomeration, and met the product quality requirements.

[0048] Example 5: Preparation of Creatine Monohydrate

[0049] The same steps and conditions were as in Example 2, except that a 20% by mass aqueous sodium octadecyl sulfate solution was added to kettle A at a rate of 0.175 g / min (0.00009 mol / min). The remaining steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, with a content of 99.9%, 18 ppm of dicyandiamide, and 21 ppm of creatinine, and a molar yield of 85.4%. The creatine particles were uniform, had good fluidity, and were not prone to agglomeration. The product quality met the requirements.

[0050] Example 6: Preparation of Creatine Monohydrate

[0051] The same steps and conditions were as in Example 2, except that a 20% aqueous sodium octadecylsulfonate solution was added to kettle A at a rate of 0.165 g / min (0.00009 mol / min). The remaining steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, having a content of 99.8%, 15 ppm of dicyandiamide, and 18 ppm of creatinine, with a molar yield of 85.3%. The creatine particles were uniform, had good fluidity, were not prone to agglomeration, and met the product quality requirements.

[0052] Example 7: Preparation of Creatine Monohydrate

[0053] The same steps and conditions were as in Example 2, except that a 20% by mass aqueous sodium lauryl sulfate solution was added to kettle A at a rate of 0.27 g / min (0.00018 mol / min). The remaining steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, having a content of 99.9%, 6 ppm of dicyandiamide, and 8 ppm of creatinine, with a molar yield of 85.8%. The creatine particles were uniform, had good fluidity, were not prone to agglomeration, and met the product quality requirements.

[0054] Example 8: Preparation of Creatine Monohydrate

[0055] 6667.4 g (18.02 mol) of a 30% sodium sarcosinate aqueous solution was continuously introduced into a bipolar membrane electrodialysis apparatus at a flow rate of 38.43 g / min to produce a sarcosine aqueous solution having a pH of 10.5. The sarcosine aqueous solution was then continuously introduced into a heat exchanger (scrapered vaporized water was used as a heat medium and the sarcosine aqueous solution was used as a coolant. The scraped vaporized water exchanged heat with the sarcosine aqueous solution, the scraped vaporized water condensed, and the sarcosine aqueous solution was heated to 10-15° C.). The solution was then continuously introduced into a scraped evaporator and concentrated by scraped water distillation (at a concentration temperature of 75-80° C.) to obtain a sarcosine concentrate having a mass concentration of 38.99%. The pH of the sarcosine concentrate was adjusted to 9.5 using a 30% aqueous hydrochloric acid solution.

[0056] Five 1000mL reactors A, B, C, D, and E were connected in series to form a continuous reactor; hot water was introduced into the reactor jacket in advance and heated to 65-70°C. The sarcosine concentrate obtained above was continuously introduced into reactor A at a flow rate of 23.71g / min (0.103mol / min), and a 20% aqueous solution of sodium lauryl sulfate as an additive was added at a flow rate of 0.17g / min (0.00012mol / min). At the same time, a 50% aqueous solution of cyanamide was introduced at a flow rate of 1.79g / min (0.021mol / min) to carry out a guanylation reaction in reactor A; the reaction solution obtained in reactor A was continuously introduced into reactor B at a flow rate of 25.67g / min, and a 50% aqueous solution of cyanamide was introduced at a flow rate of 1.79g / min to carry out a guanylation reaction in reactor B; The reaction liquid from kettle C was continuously passed into kettle C at a flow rate of 27.46 g / min, while a 50% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.79 g / min, where a guanidation reaction occurred. The reaction liquid from kettle C was continuously passed into kettle D at a flow rate of 29.25 g / min, while a 50% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.79 g / min, where a guanidation reaction occurred. The reaction liquid from kettle D was continuously passed into kettle E at a flow rate of 31.04 g / min, while a 50% aqueous cyanamide solution was simultaneously introduced at a flow rate of 1.79 g / min, where a guanidation reaction occurred. The total reaction residence time was 198 minutes. The reaction liquid from kettle E was cooled to 5°C for crystallization, centrifuged, washed, and dried to obtain creatine monohydrate with a content of 99.8%, 3 ppm dicyandiamide, and 5 ppm creatinine, with a molar yield of 85.3%. The creatine particles were uniform, had good fluidity, and were not prone to agglomeration, meeting product quality requirements.

[0057] Example 9: Preparation of Creatine Monohydrate

[0058] 5263.74 g (18.02 mol) of a 38% sodium sarcosinate aqueous solution was continuously introduced into a bipolar membrane electrodialysis apparatus at a flow rate of 24.95 g / min to produce a sarcosine aqueous solution having a pH of 9.8. The sarcosine aqueous solution was then continuously introduced into a heat exchanger (scrapered vaporized water was used as a heat medium and the sarcosine aqueous solution was used as a coolant. The scraped vaporized water exchanged heat with the sarcosine aqueous solution, the scraped vaporized water condensed, and the sarcosine aqueous solution was heated to 10-15° C.). The solution was then continuously introduced into a scraped evaporator and concentrated by scraped water distillation (at a concentration temperature of 75-80° C.) to obtain a sarcosine concentrate having a mass concentration of 48.02%. The pH of the sarcosine concentrate was adjusted to 9.2 using a 15% aqueous hydrochloric acid solution.

[0059] Four 1000mL reactors A, B, C, and D were connected in series to construct a continuous reactor; hot water was introduced into the reactor jacket in advance and heated to 60-65°C. The sarcosine concentrate obtained above was continuously introduced into reactor A at a flow rate of 15.83g / min (0.085mol / min), and a 20% aqueous solution of sodium lauryl sulfate as an additive was added at a flow rate of 0.155g / min (0.0001mol / min). At the same time, a 30% aqueous solution of monocyanamide was introduced at a flow rate of 2.99g / min (0.02mol / min) to carry out a guanidation reaction in reactor A; the reaction solution obtained in reactor A was continuously introduced into reactor B at a flow rate of 18.975g / min, and at the same time, a 20% aqueous solution of sodium lauryl sulfate as an additive was added at a flow rate of 0.155g / min (0.0001mol / min). A 30% aqueous cyanamide solution was introduced into kettle B at a flow rate of 1.0 g / min, and a guanidation reaction was carried out. The reaction liquid from kettle B was continuously introduced into kettle C at a flow rate of 21.965 g / min, while a 30% aqueous cyanamide solution was introduced at a flow rate of 2.99 g / min, and a guanidation reaction was carried out in kettle C. The reaction liquid from kettle C was continuously introduced into kettle D at a flow rate of 24.955 g / min, while a 30% aqueous cyanamide solution was introduced at a flow rate of 2.99 g / min, and a guanidation reaction was carried out in kettle D. The total reaction residence time was 186 minutes. The reaction liquid from kettle D was cooled to 5°C for crystallization, centrifuged, washed, and dried to obtain creatine monohydrate with a content of 99.8%, 7 ppm dicyandiamide, and 5 ppm creatinine, with a molar yield of 85.1%. The creatine particles were uniform, had good fluidity, and were not prone to agglomeration, meeting product quality requirements.

[0060] Comparative Example 1 (Batch Process): Preparation of Creatine Monohydrate

[0061] 526.37 g (1.80 mol) of a 38% sodium sarcosinate aqueous solution was continuously introduced into a bipolar membrane electrodialysis apparatus at a flow rate of 24.95 g / min to undergo continuous bipolar membrane electrodialysis to prepare a sarcosine aqueous solution having a pH of 9.5. The sarcosine aqueous solution was then continuously introduced into a heat exchanger (scrapered vaporized water was used as a heat medium and the sarcosine aqueous solution was used as a coolant. The scraped vaporized water exchanged heat with the sarcosine aqueous solution, the scraped vaporized water was condensed, and the sarcosine aqueous solution was heated to 10-15° C.), and then continuously introduced into a scraped evaporator to be concentrated by scraped water distillation (the concentration temperature was 75-80° C.) to obtain a sarcosine concentrate having a mass concentration of 48.0%. The pH of the sarcosine concentrate was adjusted to 9.2 using a 15% aqueous hydrochloric acid solution.

[0062] The sarcosine concentrate was added to a guanylation reaction kettle, heated to 60-65°C, and 252.28 g (1.8 mol) of a 30% cyanamide aqueous solution was added dropwise. The temperature was controlled at 60-65°C. After the addition was complete, the mixture was kept warm for 2 hours, cooled to 5°C for crystallization, centrifuged, washed, and dried to obtain creatine monohydrate with a content of 98.9%, 105 ppm of dicyandiamide, and 210 ppm of creatinine. The molar yield was 73%. However, the creatine particles were uneven, had poor fluidity, and were prone to agglomeration. The product quality did not meet the requirements.

[0063] Comparative Example 2: Preparation of Creatine Monohydrate

[0064] The same steps and conditions were as in Example 2, except that the pH of the sarcosine concentrate was adjusted to 12 using a 30% aqueous sodium hydroxide solution, and a 20% aqueous sodium lauryl sulfate solution was added to kettle A at a rate of 0.135 g / min (0.00009 mol / min). The other steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained, having a content of 98.9%, 330 ppm of dicyandiamide, and 410 ppm of creatinine, with a molar yield of 70.0%. However, the creatine contained a high level of impurities, and the product quality did not meet the requirements.

[0065] Comparative Example 3: Preparation of Creatine Monohydrate

[0066] As described in Example 2, except that no additives were added, and the other steps and conditions were the same as in Example 2. Creatine monohydrate (I) was obtained with a content of 99.1%, 210 ppm of dicyandiamide, and 230 ppm of creatinine, with a molar yield of 75%. However, the creatine particles were uneven, had poor fluidity, and easily agglomerated, and the product quality did not meet the requirements.

[0067] Comparing Comparative Example 1 with Example 9, the use of a continuous reactor and the addition of additives effectively inhibited the formation of by-products dicyandiamide and creatinine, which was more conducive to the formation of creatine. The obtained creatine had a high content, a high yield, few impurities, and significantly improved creatine crystal properties. The particles were uniform, had good fluidity, and were not easy to agglomerate.

[0068] In Comparative Example 2, the pH of the sarcosine concentrate was 12. Since the pH was too high, cyanamide was more likely to polymerize into dicyandiamide, and creatine was also easily dehydrated into creatinine, resulting in significantly high impurities and low yield.

[0069] In Comparative Example 3, no additives were added, the probability of cyanamide and creatinine formation was high, the impurities were significantly high, and the yield was low.

Claims

1. A method for preparing high-content creatine monohydrate, comprising the steps of: (1) A sodium sarcosinate (II) aqueous solution is subjected to bipolar membrane electrodialysis to continuously prepare a sarcosine (III) aqueous solution, which is then concentrated by continuous scraper distillation to obtain a sarcosine (III) concentrated solution; (2) introducing the concentrated solution of sarcosine (III), the aqueous solution of cyanamide (IV), and the additive into a continuous reactor respectively, undergoing guanidation reaction, followed by cooling, crystallization, centrifugation, washing, and drying to obtain creatine monohydrate (I); The additive is one or a combination of two or more of sodium decyl sulfate, sodium dodecyl sulfate, sodium hexadecyl sulfate, sodium octadecyl sulfate or sodium octadecyl sulfonate; 2. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), the mass concentration of the sodium sarcosinate aqueous solution is 10 to 50%, preferably 20 to 40%.

3. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), the pH of the sarcosine (III) aqueous solution is 9-11.

4. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), the sarcosine (III) aqueous solution continuously prepared by bipolar membrane electrodialysis continuously enters a heat exchanger for heat exchange, and then is continuously concentrated by scraper distillation.

5. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), the concentration temperature is 40-100° C., preferably 60-80° C.; preferably, the mass concentration of the sarcosine (III) concentrate is 20-55%, preferably 30-50%.

6. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), the pH of the sarcosine (III) concentrate is adjusted to 8 to 10 using a sodium hydroxide aqueous solution with a mass concentration of 10 to 32% or a hydrochloric acid aqueous solution with a mass concentration of 10 to 38%.

7. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (1), a sodium sarcosine (II) aqueous solution is continuously introduced into a bipolar membrane electrodialysis device to prepare a sarcosine (III) aqueous solution through continuous bipolar membrane electrodialysis; and the sarcosine aqueous solution is continuously introduced into a heat exchanger for heat exchange; Then the product is continuously passed into a scraper evaporator, and concentrated by continuous scraper evaporation to obtain a sarcosine (III) concentrate, and the pH is adjusted.

8. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (2), the mass concentration of the aqueous solution of cyanamide (IV) is 20-50%; Preferably, the additive is introduced into the continuous reactor in the form of a solid or an aqueous solution of the additive with a mass concentration of 5 to 50%.

9. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (2), the continuous reactor is composed of 3 to 8 reactors connected in series, preferably 4 to 6 reactors; the first reactor is respectively introduced with sarcosine (III) concentrated solution, cyanamide (IV) aqueous solution and additives; the other reactors are respectively introduced with the reaction solution obtained from the previous reactor and cyanamide (IV) aqueous solution; in the first reactor, the molar ratio of sarcosine (III), cyanamide (IV) and additives is (0.95 to 1.30): 1 / n: (0.001 to 0.01), preferably (0.98 to 1.1): 1 / n: (0.0011 to 0.0013), and the molar ratio of sarcosine (III) introduced into the first reactor to cyanamide introduced into each of the other reactors is (0.95 to 1.30): 1 / n, preferably (0.98 to 1.1): 1 / n, wherein n is the number of reactors.

10. The method for preparing high-content creatine monohydrate according to claim 1, characterized in that: In step (2), the guanidinization reaction temperature is 50 to 90° C., preferably 60 to 80° C.; the total reaction residence time is 120 to 360 min, preferably 180 to 300 min; Preferably, in step (2), the crystallization temperature is 0 to 25°C, preferably 5 to 15°C.

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