Preparation method of magnesium orotate

Abstract

The invention discloses a preparation method of magnesium orotate, which comprises the following steps: S1, fully mixing orotic acid and orotic acid hydrolase in water to obtain an orotic acid suspension; the dosage of the orotic acid hydrolase is 5%-10% of the mass of the orotic acid; s2, adding magnesium oxide, and reacting at 50-70 DEG C until the solution is clear; the molar ratio of the amount of the orotic acid to the amount of the magnesium oxide is 2: (1.3-1.5); s3, concentrating, crystallizing and drying to obtain the magnesium orotate. According to the method, a certain amount of orotate hydrolase is added in the reaction, so that the hydrolysis ring opening of the orotate can be promoted, the reaction degree is increased, and the magnesium orotate product with relatively high yield and purity is obtained.

Description

Technical Field

[0001] The invention belongs to the technical field of food processing, and particularly relates to a preparation method of magnesium orotate. Background Art

[0002] Magnesium is one of the important ions that maintain the excitability of nerves, muscles and heart. It is one of the essential minerals for the human body. It participates in hundreds of enzymatic reactions, can maintain normal cell function, has an inhibitory effect on the central nervous system, can play a sedative role, acts on peripheral blood vessels, dilates blood vessels, and has the effect of lowering blood pressure. As a kind of vitamin, orotic acid can be synthesized by the human body and intestinal bacteria. It is an organic acid belonging to the nucleic acid class of biochemicals. It is a substance that can be naturally produced by the intestinal flora of organisms. It has a keto structure and an enol structure. As an important intermediate product for the synthesis of uracil nucleic acid and a precursor for the biosynthesis of genetic material, it is a very important pyrimidine derivative. Orotic acid itself has a wide range of applications in the fields of medicine, food, daily chemicals and life sciences.

[0003] Combining orotic acid with magnesium can not only give full play to the advantages of orotic acid in the human body, such as no stimulation to the kidneys and low accumulation of residual substances, but also has a high biological absorption and utilization rate. At the same time, it can give full play to the physiological role of magnesium in maintaining nerve, muscle and cardiac irritability. Magnesium also has an inhibitory effect on the central nervous system, which can calm nerves, act on peripheral blood vessels in the body, dilate blood vessels, and have the effect of lowering blood pressure. In recent years, orotic acid drugs have attracted much attention for their good efficacy, few side effects, no stimulation to the kidneys, and low residual and accumulation in the body. Orotic acid is not only a component of medical vitamins, but also widely used in cosmetics as a nutritional cosmetic matrix to promote cell metabolism and delay cell aging.

[0004] However, orotic acid itself is hydrophobic, poorly soluble in water (0.18%), with a solubility of 13% in boiling water, and is very slightly soluble in alcohol and organic solvents, insoluble in ether, and is difficult to react thoroughly with other substances, resulting in low yield and purity of magnesium orotic acid.

[0005] Based on the above technical problems, the present application intends to provide a method for preparing magnesium orotate, by which a high-purity magnesium orotate product can be obtained. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing magnesium orotate in order to solve the deficiencies in the prior art.

[0007] The purpose of the present invention is achieved by the following technical solutions:

[0008] A method for preparing magnesium orotate comprises the following steps:

[0009] S1. Take orotic acid and orotic acid hydrolase and mix them in water to obtain an orotic acid suspension; the amount of the orotic acid hydrolase is 5% to 10% of the mass of the orotic acid;

[0010] S2. Then, magnesium oxide is added and reacted at 50°C to 70°C until the solution is clear; the amount of the orotic acid to the magnesium oxide is in a molar ratio of 2:(1.3 to 1.5);

[0011] S3. Concentrate, crystallize and dry to obtain magnesium orotate.

[0012] Preferably, the orotate hydrolase is dihydroorotase, and the pH of the system is adjusted to 3-4.

[0013] Preferably, citric acid is used to adjust the pH of the system.

[0014] Preferably, step S1 further comprises:

[0015] Take orotic acid and slowly add it into water of 2 to 3 times its mass, then add dihydroorotase, mix thoroughly, and adjust the pH of the system to 3 to 4 to obtain the orotic acid suspension.

[0016] Preferably, step S2 further comprises:

[0017] First, the orotic acid suspension is heated to 50° C. to 70° C., and then magnesium oxide is slowly added thereto, followed by sufficient reaction at 50° C. to 70° C. under continuous stirring.

[0018] Preferably, the reaction time in step S2 is 1 h to 2 h.

[0019] Preferably, step S3 further comprises:

[0020] First, the reactant of step S2 is separated into solid and liquid, the separated liquid phase is concentrated at high temperature, then cooled and crystallized, the solid and liquid are separated again, and the solid phase is dried.

[0021] Preferably, the concentration temperature is ≥90°C, and the concentration is performed to a liquid phase volume ≤1 / 2.

[0022] Preferably, the liquid phase is concentrated to a volume that is 1 / 2 to 1 / 3 of the original volume.

[0023] Preferably, the drying temperature in step S3 is 75° C. to 85° C., and the drying time is 16 h to 18 h.

[0024] The present application can promote the hydrolysis and ring-opening of orotic acid by adding a certain amount of orotic acid hydrolase in the reaction, thereby increasing the degree of reaction and obtaining a magnesium orotic acid product with high yield and purity. DETAILED DESCRIPTION

[0025] The present invention provides a method for preparing magnesium orotate, comprising the following steps:

[0026] S1. Take orotic acid and orotic acid hydrolase and mix them in water to obtain an orotic acid suspension; the amount of orotic acid hydrolase is 5% to 10% by mass of orotic acid;

[0027] S2. Then, magnesium oxide is added and reacted at 50°C to 70°C until the solution is clear and the magnesium oxide and orotic acid are completely reacted; the molar ratio of orotic acid to the magnesium oxide is 2:(1.3 to 1.5);

[0028] S3. Concentrate, crystallize and dry to obtain magnesium orotate.

[0029] Since orotic acid has low solubility in water and is not easy to react with magnesium oxide, the present application adopts the addition of a certain amount of orotic acid hydrolase, preferably dihydroorotic acid, which promotes the hydrolysis and ring opening of orotic acid in an acidic environment, preferably under pH 3-4 conditions, thereby increasing the degree of binding reaction between orotic acid and magnesium ions, and combining a certain high temperature to make it fully react with magnesium oxide, and then purifying through concentration and crystallization to obtain a magnesium orotic acid product with higher purity.

[0030] Because orotic acid and magnesium oxide synthesize magnesium orotate, it is to react into clear solution first, then by high temperature concentration, after solution is oversaturated, magnesium orotate product will be crystallized from solution, and the degree of reaction can not be improved by increasing reaction temperature alone, and magnesium orotate product content and yield are not greatly affected, therefore, the application adopts adding certain orotate hydrolase, promotes the hydrolysis ring opening of orotate, so as to increase the degree of reaction, and obtains the magnesium orotate product with higher yield and purity. During reaction, the application adopts excessive orotate, in order to make as much orotate hydrolysis ring opening as possible react with magnesium oxide, even if orotate reaction is incomplete, subsequent solid-liquid separation, insoluble orotate can be separated from the system, and product content will not be affected.

[0031] Preferably, step S1 further comprises:

[0032] Take orotic acid and slowly add it into water of 2 to 3 times its mass to make the orotic acid evenly dispersed in the water, then add orotic acid hydrolase, mix thoroughly, and adjust the pH of the system to 3 to 4 to obtain an orotic acid suspension. Preferably, citric acid is used to adjust the pH of the system.

[0033] Due to the excess of orotic acid, magnesium oxide will be completely reacted, so magnesium citrate will not be produced by adjusting the pH with citric acid. Even if some magnesium oxide reacts with citric acid to produce magnesium citrate, magnesium citrate is basically insoluble in the subsequent reaction solid-liquid separation step and will be separated, which will not affect the filtrate and the subsequent magnesium orotic acid product content.

[0034] Preferably, step S2 further comprises:

[0035] First, the orotic acid suspension is heated to 50°C to 70°C, and then magnesium oxide is slowly added, and then fully reacted at 50°C to 70°C under continuous stirring.

[0036] In order to make the reaction as thorough as possible while taking into account the reaction efficiency, preferably, the reaction time is 1 h to 2 h.

[0037] Preferably, step S3 further comprises:

[0038] First, the step S2 reactant solid-liquid separation is taken, and unreacted orotic acid is isolated, and the liquid phase after separation is concentrated at high temperature, then cooled and crystallized, and solid-liquid separation is performed again, and solid phase drying is taken. Solid-liquid separation method can adopt methods such as filtration and centrifugation. Magnesium orotate has certain solubility in water, and can not be directly crystallized by cooling, therefore, the application is first concentrated, and through high temperature concentration, water volume is reduced, and solution is supersaturated, and correspondingly magnesium orotate dissolution amount is reduced, and crystallization is precipitated after cooling.

[0039] More preferably, the concentration temperature is ≥90°C, and the concentration is performed until the liquid phase volume is ≤1 / 2. Further, the concentration is performed until the liquid phase volume is 1 / 2 to 1 / 3 of the original volume.

[0040] Preferably, the drying temperature in step S3 is 75° C. to 85° C. and the drying time is 16 h to 18 h. Within this range, the wet magnesium orotate can be fully dried to remove crystal water without causing adverse changes in properties.

[0041] Example 1

[0042] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0043] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 30 g of dihydroorotase, stir well, and adjust the pH of the system to 3.5 with citric acid to obtain orotic acid suspension①;

[0044] 2. Heat the orotic acid suspension ① in step 1 to 60°C, slowly add 52g of magnesium oxide to ①, stir well to react, and react for 1.5h until the solution becomes clear;

[0045] 3. After filtration, concentrate the filtrate at 95°C to 1 / 2 of its volume, stop heating, stir and cool to room temperature, then filter and separate;

[0046] 4. After sufficient separation, the wet material was dried in a blast drying oven at 80°C for 17 hours to obtain a white crystalline powder magnesium orotate product.

[0047] Comparative Example 1

[0048] Except that the reaction temperature in step 2 is replaced with 40° C., the rest is the same as in Example 1.

[0049] Comparative Example 2

[0050] Except that the reaction temperature in step 2 is replaced with 80° C., the rest is the same as in Example 1.

[0051] Comparative Example 3

[0052] Except that the reaction temperature in step 2 is replaced with 95° C., the rest is the same as in Example 1.

[0053] The magnesium orotate products of Example 1 and Comparative Examples 1 to 3 were compared and analyzed, and the analysis results of the effects of different reaction temperatures on the magnesium orotate products are shown in Table 1.

[0054] Table 1 Effect of different reaction temperatures on the synthesis of magnesium orotate products

[0055] Sample No. Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Reaction temperature / ℃ 60℃ 40℃ 80℃ 95℃ Magnesium orotate content / % 99.68 70.21 80.30 66.8 Product yield / % 80.3 50.8 62.9 45.5

[0056] Comparison Table 1 data show that the reaction temperature in the process of synthesizing magnesium orotate has a greater impact on product content and yield. A higher reaction temperature will affect the activity of orotate hydrolase, reduce the degree of hydrolysis of orotate, thereby reducing the reaction rate of orotate and magnesium oxide, resulting in a decrease in product content and yield. Therefore, the synthesis reaction temperature of magnesium orotate should be maintained at 50°C to 70°C, preferably 60°C.

[0057] Comparative Example 4

[0058] The addition ratio (molar ratio) of orotic acid and magnesium oxide raw materials was changed from the original 2:1.3 to 2:1, and the remaining steps and operations were the same as in Example 1.

[0059] Comparative Example 5

[0060] The ratio (molar ratio) of orotic acid and magnesium oxide raw materials added was changed from the original 2:1.3 to 2:1.2, and the remaining steps and operations were the same as in Example 1.

[0061] Comparative Example 6

[0062] Except that the addition ratio (molar ratio) of orotic acid and magnesium oxide raw materials was changed from the original 2:1.3 to 2:1.4, the remaining steps and operations were the same as those in Example 1.

[0063] Comparative Example 7

[0064] Except that the addition ratio (molar ratio) of orotic acid and magnesium oxide raw materials was changed from the original 2:1.3 to 2:1.5, the remaining steps and operations were the same as those in Example 1.

[0065] The magnesium orotate products of Example 1 and Comparative Examples 4 to 7 were compared and analyzed, and the results of the analysis of the effects of different raw material ratios on the magnesium orotate products are shown in Table 2.

[0066] Table 2 Effect of different raw material ratios on the synthesis of magnesium orotate products

[0067] Sample No. Example 1 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Raw material ratio 2:1.3 2:1.1 2:1.2 2:1.4 2:1.5 Magnesium orotate content / % 99.68 95.13 96.75 100.24 100.56 Product yield / % 80.3 68.3 72.3 80.5 81.1

[0068] Comparison Table 2 data shows that the feed ratio of raw materials will affect the product content and yield. The raw material ratio <2:1.3 will reduce the magnesium orotate product content and the yield. The raw material ratio >2:1.3 will react more fully to a certain extent, but the effect of improving the magnesium orotate product content and yield is not great. Therefore, the feed ratio of raw materials should be between 2:1.3 and 1.5, and it should be preferably 2:1.3 considering the preparation cost.

[0069] Comparative Example 8

[0070] Except that in step 4 of the process of synthesizing magnesium orotate, the drying temperature is changed to 60° C., the rest is the same as in Example 1.

[0071] Comparative Example 9

[0072] Except that in step 4 of the process of synthesizing magnesium orotate, the drying temperature is changed to 80° C., the rest is the same as in Example 1.

[0073] Comparative Example 10

[0074] Except that in step 4 of the process of synthesizing magnesium orotate, the drying temperature is changed to 100° C., the rest is the same as in Example 1.

[0075] The magnesium orotate products of Example 1 and Comparative Examples 8 to 10 were compared and analyzed, and the results of the analysis of the effects of different drying conditions on the synthesis of magnesium orotate products are shown in Table 3.

[0076] Table 3 Effect of different drying conditions on the synthetic magnesium orotate product

[0077] Sample No. Example 1 Comparative Example 11 Comparative Example 12 Comparative Example 13 Drying temperature 80 60 70 90 Magnesium orotate content / % 99.68 94.51 96.86 99.69 Loss on drying / % 0.33 7.21 5.12 0.26

[0078] Comparing the data in Table 3, it can be seen that different drying conditions have a greater influence on the moisture content of the synthetic magnesium orotate product. The higher the drying temperature, the lower the moisture content of the magnesium orotate product. However, the degree of reduction in the moisture content of the product is no longer obvious when the drying temperature is greater than 85°C. Considering the synthesis cost of the product, the product drying temperature should be between 75°C and 85°C.

[0079] Comparative Example 11

[0080] Except that the concentration degree in step 3 is changed to 1 / 4 of the original volume, the rest is the same as in Example 1.

[0081] Comparative Example 12

[0082] Except that the concentration degree in step 3 is changed to 1 / 3 of the original volume, the rest is the same as in Example 1.

[0083] The magnesium orotate products of Example 1 and Comparative Examples 11 to 12 were compared and analyzed, and the analysis results of the effects of different concentration levels on the synthesis of magnesium orotate products are shown in Table 4.

[0084] Table 4 Effect of different concentration levels on the synthesis of magnesium citrate products

[0085] Sample No. Example 1 Comparative Example 7 Comparative Example 8 Concentration degree / ml 1 / 2 1 / 4 1 / 3 Magnesium orotate content / % 100.28 97.30 99.52 Product yield / % 95.3 70.6 88.5

[0086] Comparison Table 4 data show that the degree of concentration in the process of synthesizing magnesium orotate has a greater impact on product content and yield. Too high or too low a degree of concentration will affect the crystallization of magnesium orotate, resulting in a significant decrease in product yield. Therefore, the degree of concentration of the reaction solution should be maintained between 1 / 3 and 1 / 2, preferably 1 / 2.

[0087] Example 2

[0088] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0089] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 30 g of orotic acid hydrolase, stir well, and adjust the pH of the system to 3.5 with citric acid to obtain orotic acid suspension ①;

[0090] 2. Heat the orotic acid suspension ① in step 1 to 50°C, slowly add 52g of magnesium oxide to ①, stir and react for 1.5h, react until the solution is clear and filter;

[0091] 3. After filtration, concentrate the filtrate to 1 / 2 of its volume at high temperature, stop heating, stir and cool to room temperature, then filter and separate;

[0092] 4. After sufficient separation, the wet material is dried in a blast drying oven at 80°C for 16 hours to obtain a white crystalline powder of magnesium orotate.

[0093] Example 3

[0094] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0095] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 30 g of orotic acid hydrolase, stir well, and adjust the pH of the system to 3.5 with citric acid to obtain orotic acid suspension ①;

[0096] 2. Heat the orotic acid suspension ① in step 1 to 55°C, slowly add 52g of magnesium oxide to ①, stir and react for 1.5h, react until the solution is clear and filter;

[0097] 3. After filtration, concentrate the filtrate to 1 / 2 of its volume at high temperature, stop heating, stir and cool to room temperature, then filter and separate;

[0098] 4. After sufficient separation, the wet material is dried in a blast drying oven at 80°C for 16 hours to obtain a white crystalline powder of magnesium orotate.

[0099] Example 4

[0100] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0101] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 30 g of orotic acid hydrolase, stir well, and adjust the pH of the system to 3.5 with citric acid to obtain orotic acid suspension ①;

[0102] 2. Heat the orotic acid suspension ① in step 1 to 65°C, slowly add 52g of magnesium oxide to ①, stir and react for 1.5h, react until the solution is clear and filter;

[0103] 3. After filtration, concentrate the filtrate to 1 / 2 of its volume at high temperature, stop heating, stir and cool to room temperature, then filter and separate;

[0104] 4. After sufficient separation, the wet material is dried in a blast drying oven at 80°C for 16 hours to obtain a white crystalline powder of magnesium orotate.

[0105] Example 5

[0106] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0107] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 30 g of orotic acid hydrolase, stir well, and adjust the pH of the system to 3.5 with citric acid to obtain orotic acid suspension ①;

[0108] 2. Heat the orotic acid suspension ① in step 1 to 70°C, slowly add 52g of magnesium oxide to ①, stir and react for 1.5h, react until the solution is clear and filter;

[0109] 3. After filtration, concentrate the filtrate to 1 / 2 of its volume at high temperature, stop heating, stir and cool to room temperature, then filter and separate;

[0110] 4. After sufficient separation, the wet material is dried in a blast drying oven at 80°C for 16 hours to obtain a white crystalline powder of magnesium orotate.

[0111] Table 5 Example Synthesis of Magnesium Orotate Product Data

[0112] Sample No. Example 2 Example 3 Example 4 Example 5 Reaction temperature / ℃ 50℃ 55℃ 65℃ 70℃ Magnesium orotate content / % 98.65 99.02 99.46 99.68 Product yield / % 95.1 95.6 95.8 96.1

[0113] Example 6

[0114] The preparation method of magnesium orotate provided in this embodiment comprises the following steps:

[0115] 1. Add 800 ml of deionized water to a 1L beaker, slowly add 312 g of orotic acid, then add 12 g of orotic acid hydrolase, stir well, and adjust the pH of the system to 4 with citric acid to obtain orotic acid suspension ①;

[0116] 2. Heat the orotic acid suspension ① in step 1 to 60°C, slowly add 52g of magnesium oxide to ①, stir and react for 2h, react until the solution is clear and filter;

[0117] 3. After filtration, concentrate the filtrate to 1 / 2 of its volume at high temperature, stop heating, stir and cool to room temperature, then filter and separate;

[0118] 4. After sufficient separation, the wet material is dried in a blast drying oven at 75°C for 18 hours to obtain a white crystalline powder of magnesium orotate.

[0119] Although preferred embodiments of the present invention have been described, additional changes and modifications may be made to these embodiments by those skilled in the art once the basic inventive concepts are known. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention. Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing magnesium orotate, characterized in that: The following steps are involved: S1. Take orotic acid and orotic acid hydrolase and mix them in water to obtain an orotic acid suspension; the amount of the orotic acid hydrolase is 5% to 10% of the mass of the orotic acid; S2. Then, magnesium oxide is added and reacted at 50°C to 70°C until the solution is clear; the amount of the orotic acid to the magnesium oxide is in a molar ratio of 2:(1.3 to 1.5); S3. Concentrate, crystallize and dry to obtain magnesium orotate.

2. The method for preparing magnesium orotate according to claim 1, wherein The orotate hydrolase is dihydroorotase, and the pH of the system is adjusted to 3-4.

3. The method for preparing magnesium orotate according to claim 2, wherein Citric acid was used to adjust the pH of the system.

4. The method for preparing magnesium orotate according to claim 2, wherein: Step S1 further comprises: Take orotic acid and slowly add it into water of 2 to 3 times its mass, then add dihydroorotase, mix thoroughly, and adjust the pH of the system to 3 to 4 to obtain the orotic acid suspension.

5. The method for preparing magnesium orotate according to claim 1, wherein Step S2 further comprises: First, the orotic acid suspension is heated to 50° C. to 70° C., and then magnesium oxide is slowly added thereto, followed by sufficient reaction at 50° C. to 70° C. under continuous stirring.

6. The method for preparing magnesium orotate according to claim 1, characterized in that, The reaction time of step S2 is 1 h to 2 h.

7. The method for preparing magnesium orotate according to claim 1, wherein Step S3 further comprises: First, the reactant of step S2 is separated into solid and liquid, the separated liquid phase is concentrated at high temperature, then cooled and crystallized, the solid and liquid are separated again, and the solid phase is dried.

8. The method for preparing magnesium orotate according to claim 7, characterized in that, The concentration temperature is ≥90°C, and the concentration is performed until the liquid phase volume is ≤1 / 2.

9. The method for preparing magnesium orotate according to claim 8, wherein: Concentrate until the liquid phase volume is 1 / 2 to 1 / 3 of the original volume.

10. The method for preparing magnesium orotate according to claim 1, characterized in that: The drying temperature in step S3 is 75° C. to 85° C., and the drying time is 16 h to 18 h.