Preparation method of high-purity calcium ketoglutarate

Abstract

The invention discloses a preparation method of high-purity calcium ketoglutarate. According to the method, calcium hydroxide is used as a calcium source, so that impurities generated in the process of introducing other alkalis to neutralize ketoglutaric acid are reduced, and introduction of chloride ions is avoided from the source; excessive calcium hydroxide is added, the solubility difference between calcium hydroxide and calcium ketoglutarate is utilized, residual calcium hydroxide is dissolved with glycerin, and mixed precipitate is purified. The method is simple in process and convenient to operate, the produced alpha-ketoglutarate calcium chloride ion content is low, the product is safe and high in purity, the defects of an existing process can be overcome, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of organic trace element chelate processing, and in particular to a method for preparing high-purity calcium ketoglutarate. Background Art

[0002] Calcium α-ketoglutarate is a stable form of AKG. As an intermediate product of the TCA cycle, calcium α-ketoglutarate participates in the process of generating energy in cells, which can promote the energy metabolism of cells, improve the energy level of the body, help to enhance physical strength and endurance, and improve physical fatigue. In addition, in the process of amino acids being converted into other metabolites, calcium α-ketoglutarate undergoes transamination with amino acids to generate new amino acids or α-keto acids, thereby regulating the balance and utilization of amino acids. In addition, calcium α-ketoglutarate can also serve as an oxidation substrate for amino acids, participate in the oxidative metabolism of amino acids, and produce energy and carbon dioxide. Therefore, calcium α-ketoglutarate is of great significance for maintaining the homeostasis of amino acids and the body's protein metabolism.

[0003] α-ketoglutarate calcium is generally prepared by neutralizing α-ketoglutaric acid to neutrality with sodium hydroxide to form ketoglutaric acid disalt, and finally adding calcium chloride to generate calcium salt precipitation. However, ketoglutaric acid is unstable during the neutralization process, and the impurities generated in the process can also generate calcium salt precipitation, affecting the quality of the product. Although some researchers have used inorganic salts and ammonia water to adjust the pH of the feed solution in two steps in order to reduce impurities in the precipitate, the process is relatively complicated, the amount of ammonia water added is not easy to control during industrial production, and the pungent smell of ammonia water affects the sensory perception of the final product. In addition, since calcium chloride is used as the calcium source, a large amount of chloride ions remain in the final product, affecting product safety.

[0004] Some researchers also use calcium hydroxide or calcium carbonate to directly neutralize ketoglutaric acid to generate a-ketoglutaric acid calcium salt, but this method is likely to leave calcium hydroxide or calcium carbonate residues in the product, directly affecting product quality.

[0005] Therefore, a new solution needs to be proposed to solve this problem. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a preparation method of high-purity alpha-ketoglutarate calcium. The alpha-ketoglutarate calcium prepared by the present invention has high purity and low chloride content, and the operation process is simple and suitable for industrial production; and the glycerol used in the preparation method of the present invention can be recycled, is green and environmentally friendly, and reduces the production cost.

[0007] The technical solution adopted by the present invention to solve the above technical problems is: A method for preparing high-purity calcium ketoglutarate comprises the following steps: step 1, fully reacting excess calcium hydroxide with a liquid of α-ketoglutaric acid, filtering to obtain a mixed precipitate a of α-ketoglutarate and calcium hydroxide; step 2, adding glycerol to the precipitate a and stirring to dissolve excess calcium hydroxide impurities, filtering to obtain a precipitate b and a filtrate a, and drying the precipitate b to obtain calcium α-ketoglutarate.

[0008] Furthermore, in the step 1, the molar ratio of the α-ketoglutaric acid to calcium hydroxide is 1:(1.1-2.5).

[0009] Furthermore, in the step 1, the reaction system temperature is 40-90° C., and the reaction time is 2-6 hours.

[0010] Furthermore, in the step 2, the volume ratio of the precipitate a to glycerol is 1:(0.05-0.43).

[0011] Furthermore, in the step 2, the stirring time of adding glycerol is 0.1 to 1 hour.

[0012] Furthermore, in the step 2, the drying temperature of the precipitate b is 60-90°C.

[0013] Due to the increase of solutes, the separation effect is weakened when glycerol is reused, which increases the production cost. The present invention also proposes a method for improving the utilization rate of glycerol: sodium carbonate is added to glycerol containing calcium hydroxide, the pH is adjusted to 8-9, and the calcium carbonate precipitate is filtered to remove the filtrate b. The filtrate b can be further used to separate and purify the precipitate a. The sodium hydroxide that is continuously accumulated in the filtrate b is first saponified with glycerol by heating to generate basic fatty acid sodium salt; then calcium oxide is added to react, and the generated soap calcium is filtered to remove to obtain pure glycerol, which is further used to separate and purify the precipitate a. The glycerol can be recycled, which is green and environmentally friendly and reduces the production cost.

[0014] Therefore, the present invention also provides a method for preparing high-purity calcium ketoglutarate, comprising the following steps: Step 1, fully reacting excess calcium hydroxide with a liquid of α-ketoglutaric acid, and filtering to obtain a mixed precipitate a of calcium α-ketoglutarate and calcium hydroxide; Step 2, adding glycerol to the mixed precipitate a and stirring to dissolve excess calcium hydroxide impurities, filtering to obtain precipitate b and filtrate a, and drying the precipitate b to obtain calcium α-ketoglutarate; Step 3: adding sodium carbonate to the filtrate a, adjusting the pH to 8-9, filtering to remove the calcium carbonate precipitate, and obtaining a filtrate b; heating the filtrate b to 50-90° C., adding calcium oxide, and filtering to remove the soap calcium precipitate; obtaining a glycerol recovery; Step 4: Using the recovered glycerol in step 3 as the glycerol in step 2.

[0015] Compared with the prior art, the advantages of the present invention are as follows: the present invention discloses a method for preparing high-purity calcium ketoglutarate. The method uses calcium hydroxide as a calcium source, which not only reduces the impurities generated in the process of introducing other alkalis to neutralize ketoglutaric acid, but also avoids the introduction of chloride ions from the source; by adding an excess of calcium hydroxide, utilizing the solubility difference between calcium hydroxide and calcium ketoglutarate, using glycerol to dissolve the remaining calcium hydroxide, and purifying the mixed precipitate. The calcium hydroxide dissolved in glycerol is removed, the utilization rate of glycerol is improved, the recycling rate is increased, and impurities in glycerol are removed by saponification reaction, so that glycerol can be recycled. The process is simple and easy to operate. The chloride ion content of the produced α-calcium ketoglutarate is low, the product is safe and has high purity, which can make up for the shortcomings of the existing process and is suitable for industrial production. DETAILED DESCRIPTION

[0016] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the embodiments of the present invention will be clearly and completely described below. The described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0017] As used herein, the terms "comprising," "including," "having," "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0018] When amount, concentration or other value or parameter is expressed with range, preferred range, or a series of upper preferred values ​​and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value and any range lower limit or preferred value, regardless of whether the range is disclosed separately. For example, when disclosing range "1 to 5", the described range should be interpreted as including range "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5" etc. When numerical range is described in this article, unless otherwise stated, the range is intended to include its end value and all integers and fractions within the range.

[0019] In addition, the technical features involved in various embodiments of the present invention can be combined with each other as long as they do not conflict with each other. Example 1

[0020] 73g of α-ketoglutaric acid was placed in a 500mL beaker containing 110ml of deionized water, the system temperature was controlled at 50°C, stirred until the α-ketoglutaric acid was completely dissolved, 40.76g of calcium hydroxide was added, the stirring reaction was continued for 5 hours, and the mixture was placed at 5-10°C for crystallization for two hours and filtered. 0.05 times the volume of glycerol was added to the filter cake, and the mixture was filtered again after stirring for 20 minutes. The filter cake was dried at 60-90°C for 10 hours to obtain α-ketoglutaric acid calcium salt with a yield of 93.58%. The purity of the product was 99.89% by HPLC. The filtrate can remove impurities in glycerol and realize the recycling of glycerol by the following steps: 40g of sodium carbonate was added to the filtrate, and after filtering to remove the precipitate, the mixture was heated to 90°C, 21.1g of calcium oxide was added, and the precipitate was removed by filtering to obtain high-purity glycerol. Example 2

[0021] 73g of α-ketoglutaric acid was placed in a 500mL beaker containing 110ml of deionized water, the system temperature was controlled at 60°C, stirred until the α-ketoglutaric acid was completely dissolved, 66.69g of calcium hydroxide was added, the reaction was continued to stir for 4 hours, and filtered after being placed at 5-10°C for two hours for crystallization. 0.29 times the volume of glycerol was added to the filter cake, and the filter cake was filtered again after stirring for 20 minutes. The filter cake was dried at 60-90°C for 10 hours to obtain α-ketoglutaric acid calcium salt with a yield of 95.73%. The purity of the product was 99.95% by HPLC. The filtrate can remove impurities in glycerol and realize the recycling of glycerol by the following steps: 28g of sodium carbonate was added to the filtrate, and after filtering to remove the precipitate, the temperature was raised to 70°C, 14.8g of calcium oxide was added, and the precipitate was filtered to obtain high-purity glycerol. Example 3

[0022] 73g of α-ketoglutaric acid was placed in a 500mL beaker containing 110ml of deionized water, the system temperature was controlled at 70°C, stirred until the α-ketoglutaric acid was completely dissolved, 92.625g of calcium hydroxide was added, the reaction was continued to stir for 3 hours, and filtered after being placed at 5-10°C for two hours for crystallization. 0.43 times the volume of glycerol was added to the filter cake, and the filter cake was filtered again after stirring for 20 minutes. The filter cake was dried at 60-90°C for 10 hours to obtain α-ketoglutaric acid calcium salt with a yield of 95.86%. The purity of the product was 99.98% by HPLC. The filtrate can remove impurities in glycerol and realize the recycling of glycerol by the following steps: 16g of sodium carbonate was added to the filtrate, and after filtering to remove the precipitate, the temperature was raised to 50°C, 8.5g of calcium oxide was added, and the precipitate was filtered to obtain high-purity glycerol. Example 4

[0023] 73g α-ketoglutaric acid was loaded into a 500mL beaker containing 110ml deionized water, the system temperature was controlled at 60°C, stirred until α-ketoglutaric acid was completely dissolved, 66.69g calcium hydroxide was added, the stirring reaction was continued for 4 hours, and the mixture was placed at 5-10°C for two hours for crystallization and filtered. 0.29 times the volume of glycerol was added to the filter cake, and the impurities in Example 1 were removed, and the mixture was stirred for 20 minutes and filtered again. The filter cake was dried at 60-90°C for 10 hours to obtain α-ketoglutaric acid calcium salt, with a yield of 95.66%, and the product purity was 99.91% detected by HPLC. The filtrate can remove impurities in glycerol by the following steps to realize the recycling of glycerol: 28g sodium carbonate was added to the filtrate, and after filtering to remove the precipitate, the mixture was warmed to 70°C, 14.8g calcium oxide was added, and the precipitate was removed by filtering to obtain high-purity glycerol.

Claims

1. A method for preparing high-purity calcium ketoglutarate, characterized in that: The steps include: Step 1, fully reacting excess calcium hydroxide with a liquid of α-ketoglutaric acid, and filtering to obtain a mixed precipitate a of calcium α-ketoglutarate and calcium hydroxide; Step 2: Add glycerol to the precipitate a and stir to dissolve excess calcium hydroxide impurities, filter to obtain precipitate b, and dry the precipitate b to obtain calcium α-ketoglutarate.

2. The method for preparing high-purity calcium ketoglutarate according to claim 1, characterized in that: In the step 1, the molar ratio of α-ketoglutaric acid to calcium hydroxide is 1:(1.1-2.5).

3. The method for preparing high-purity calcium ketoglutarate according to claim 1, characterized in that: In the step 1, the reaction system temperature is 40-90° C., and the reaction time is 2-6 hours.

4. The method for preparing high-purity calcium ketoglutarate according to claim 1, characterized in that: In the step 2, the volume ratio of the precipitate a to glycerol is 1:(0.05-0.43).

5. The method for preparing high-purity calcium ketoglutarate according to claim 1, characterized in that: In the step 2, the stirring time of adding glycerol is 0.1 to 1 hour.

6. The method for preparing high-purity calcium ketoglutarate according to claim 1, characterized in that: In the step 2, the drying temperature of the precipitate b is 60-90°C.

7. A method for preparing high-purity calcium ketoglutarate, characterized in that: The steps include: Step 1, fully reacting excess calcium hydroxide with a liquid of α-ketoglutaric acid, and filtering to obtain a mixed precipitate a of calcium α-ketoglutarate and calcium hydroxide; Step 2, adding glycerol to the mixed precipitate a and stirring to dissolve excess calcium hydroxide impurities, filtering to obtain precipitate b and filtrate a, and drying the precipitate b to obtain calcium α-ketoglutarate; Step 3, adding sodium carbonate to the filtrate a, adjusting the pH to 8-9, filtering to remove the calcium carbonate precipitate, and obtaining a filtrate b; heating the filtrate b to 50-90° C., adding calcium oxide, and filtering to remove the soap calcium precipitate; obtaining glycerol recovery; Step 4: Using the recovered glycerol in step 3 as the glycerol in step 2.