A method for ion exchange purification of l-arginine

Abstract

The application discloses an L-arginine ion exchange impurity removal method and belongs to the technical field of amino acid impurity removal. In order to solve the technical problems of low yield and low purity of the L-arginine production method in the prior art and the problem that the method is not suitable for industrial large-scale production, the application provides an L-arginine ion exchange impurity removal method. In the impurity removal method, 0.15% industrial-grade ammonium chloride solution is used as a washing liquid, L-arginine fermentation liquid adsorbed by strong acid cation exchange resin is subjected to ion exchange impurity removal, and calcium ions, magnesium ions, pigment impurities and amino acids with low isoelectric points are removed. The L-arginine ion exchange impurity removal method provided by the application can simplify the anion exchange resin adsorption, activated carbon decolorization and nanofiltration organic membrane treatment process steps in the traditional L-arginine impurity removal process, reduce the L-arginine extraction cost, improve the yield and purity of L-arginine, and can be applied to industrial large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of amino acid impurity removal technology, and relates to an amino acid ion exchange impurity removal method. Background Technology

[0002] L-arginine is a basic amino acid containing a guanidine group. In its pure form, it is a white crystalline powder. It is widely present in various organisms and plays an important role in the growth, development, and metabolism of humans and animals. It is a raw material for the synthesis of proteins and creatine in the human body and an important intermediate metabolite in the urea cycle of organisms. L-arginine is a non-essential amino acid for healthy adults, but its synthesis in the body is relatively slow. It is an essential amino acid for infants and young children. Therefore, L-arginine is a semi-essential amino acid.

[0003] Currently, the main method for producing L-arginine is fermentation. However, during the extraction process from microbial fermentation broth, L-arginine exhibits low yield and low purity, making it unsuitable for large-scale industrial production. Existing technologies primarily employ ion exchange with strongly acidic cation exchange resins for the separation of impurities in L-arginine. However, because these resins also adsorb pigments, proteins, and other amino acids, these substances are often carried along with the high-flow fraction during ammonia elution, failing to achieve the desired impurity separation. Summary of the Invention

[0004] This invention addresses the technical problems of low yield and low purity in existing L-arginine production methods, making them unsuitable for large-scale industrial production, by providing an L-arginine ion exchange method for impurity removal.

[0005] The purpose of this invention is to provide a method for removing impurities from L-arginine through ion exchange, the method comprising the following steps:

[0006] S1: Filter the L-arginine fermentation broth through a ceramic membrane, collect the clear liquid from the ceramic membrane, and adjust the pH of the clear liquid from the ceramic membrane.

[0007] S2: The clear liquid from the ceramic membrane after pH adjustment in S1 is adsorbed by a strong acid cation exchange resin according to the flow rate.

[0008] S3: Prepare a washing solution, control the temperature of the washing solution to be the same as that of the strong acid cation exchange resin in S2, and add the washing solution to the strong acid cation exchange resin in S2 at a certain flow rate to wash, thereby obtaining L-arginine washing solution.

[0009] S4: The L-arginine washing solution obtained in S3 was subjected to a strong acid cation exchange resin analysis using ammonia water at a certain flow rate to obtain a high-flow fraction of ion-exchanged L-arginine.

[0010] S5: The high-flow-rate L-arginine obtained in S4 is subjected to multi-effect evaporation and then discharged, concentrated and crystallized to obtain wet L-arginine crystals.

[0011] S6: The wet L-arginine crystals obtained in S5 are centrifuged and dried to obtain L-arginine after impurity removal.

[0012] In a preferred embodiment of the present invention, the pH value in S1 is adjusted to 3-3.5.

[0013] In a preferred embodiment of the present invention, the flow rate in S2 is 0.5-0.7 BV.

[0014] In a preferred embodiment of the present invention, the step of adsorption by the strongly acidic cation exchange resin in S2 is as follows: the clear liquid of the ceramic membrane after pH adjustment is fed onto the ion exchange column at a flow rate of 0.5-0.7 BV, the ion exchange column is filled with strongly acidic cation exchange resin, and the resin adsorption saturation is considered to be when the arginine content in the effluent after exchange reaches 30%-40% of the feed content.

[0015] In a preferred embodiment of the present invention, the washing liquid in S3 is a 0.15% industrial grade ammonium chloride solution, the flow rate is 1 BV, and the washing time is 1.5 h.

[0016] In a preferred embodiment of the present invention, the ammonia concentration in S4 is 5-6%, and the flow rate is 0.5-0.7 BV.

[0017] In a preferred embodiment of the present invention, the end standard of the multi-effect evaporation treatment in S5 is that the multi-effect evaporation reaches 10%-11% of the dry matter.

[0018] In a preferred embodiment of the present invention, the concentration and crystallization process described in S5 involves placing the high flow fraction after multi-effect evaporation into a single-effect crystallizer for concentration and crystallization to 550-600 g / L, and the concentration and crystallization process is carried out at a temperature of 50-60°C.

[0019] In a preferred embodiment of the present invention, the centrifugation process in S6 is to use a filter bag centrifuge for solid-liquid separation, and to wash with pure water at 5% of the volume of wet crystals.

[0020] In a preferred embodiment of the present invention, the drying process described in S6 is performed using either a fluidized bed or a double cone apparatus.

[0021] The beneficial effects of this invention are:

[0022] This invention provides a method for removing impurities from L-arginine using ion exchange. The method involves adding an ion exchange column with a 0.15% industrial-grade ammonium chloride solution as the washing liquid. The ammonium chloride solution is used to remove impurities from the L-arginine fermentation broth adsorbed by a strongly acidic cation exchange resin through ion exchange. Since ammonium chloride decomposes in water into hydrogen ions, hydroxide ions, ammonia ions, and chloride ions, the cationic ammonia ions and hydrogen ions can exchange with the strongly acidic cation exchange resin. This process can displace calcium and magnesium ions, pigment impurities, and amino acids with low isoelectric points adsorbed on the resin, thereby achieving impurity removal and improving the purity of the effluent from the strongly acidic cation exchange resin, increasing the L-arginine yield to 86.7%.

[0023] The L-arginine ion exchange purification method provided by this invention simplifies the traditional L-arginine purification process, which involves anion exchange resin adsorption, activated carbon decolorization, and nanofiltration organic membrane treatment. This reduces the extraction cost of L-arginine and yields L-arginine with high purity, making it suitable for large-scale industrial production. Detailed Implementation

[0024] Those skilled in the art can refer to the content of this document and appropriately improve the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments, and those skilled in the art can obviously make modifications or appropriate alterations and combinations to the methods and applications described herein without departing from the content and scope of this invention to implement and apply the technology of this invention.

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the materials, reagents, methods, and instruments used are all conventional materials, reagents, methods, and instruments in the art, and can be obtained commercially by those skilled in the art.

[0026] Example 1

[0027] S1: Filter the L-arginine fermentation broth through a ceramic membrane, collect the clear liquid from the ceramic membrane, and adjust the pH of the clear liquid from the ceramic membrane to 3-3.2;

[0028] S2: The pH-adjusted ceramic membrane solution from S1 is subjected to adsorption with a strong acid cation exchange resin at a flow rate of 0.6 BV. The adsorption process is as follows: the pH-adjusted ceramic membrane solution is fed into three sets (1#, 2#, and 3#) of ion exchange columns at a flow rate of 0.6 BV. The ion exchange columns are filled with strong acid cation exchange resin. The resin adsorption is considered saturated when the arginine content in the effluent reaches 30%-40% of the feed content. Then, purified water is introduced into the three sets of ion exchange columns at a flow rate of 1 BV, with a volume of 2 BV, to replace the remaining solution in the ion exchange columns.

[0029] S3: Prepare washing solutions, which are industrial-grade ammonium chloride solutions of 0%, 0.15%, and 0.3% respectively. Control the temperature of the washing solutions to be the same as that of the strongly acidic cation exchange resin in S2. Add the washing solutions to the strongly acidic cation exchange resin in S2 at a flow rate of 1 BV for washing. The washing time is 1.5 h, and the corresponding L-arginine washing solutions are obtained.

[0030] Effect Experiment:

[0031] In this embodiment, three ion exchange columns with different washing solution concentrations are set up respectively. Ion exchange column 1 uses water as washing solution, ion exchange column 2 uses 0.15% industrial grade ammonium chloride solution as washing solution, and ion exchange column 3 uses 0.3% industrial grade ammonium chloride solution as washing solution.

[0032] In this embodiment, three sets of ion exchange columns (1#, 2#, and 3#) were used for washing for 1.5 hours. The contents of arginine, glutamic acid, lysine, and alanine in the obtained L-arginine washing solution were detected. The results are shown in Table 1. The ion exchange column using water as the washing solution (1#) only had a purification effect on glutamic acid. The ion exchange columns using 0.15% (2#) and 0.3% (3#) industrial-grade ammonium chloride solutions as washing solutions all had a certain purification effect on glutamic acid, lysine, and alanine. When the washing solution concentration was 0.3% industrial-grade ammonium chloride solution, although it had a good purification effect on glutamic acid and lysine, it also had a certain removal effect on L-arginine, thus leading to a decrease in the yield of L-arginine.

[0033] Table 1

[0034] 1# 0 0.1 0 0 2# 0 0.3 0.2 0.16 3# 0.12 0.32 0.22 0.15

[0035] In this embodiment, ion exchange column #1 was used for washing. The L-arginine washing solution was collected at 0.5h, 1h, and 1.5h for the determination of arginine, glutamic acid, lysine, and alanine content. The results are shown in Table 2. The ion exchange column using water as the washing solution (#1) only effectively removed impurities from glutamic acid during washing.

[0036] Table 2

[0037] 0.5h 0 0.1 0 0 1h 0 0.13 0 0 1.5h 0 0.08 0 0

[0038] In this embodiment, ion exchange column #2 was used for washing. The L-arginine washing solution was collected at 0.5h, 1h, and 1.5h for the determination of arginine, glutamic acid, lysine, and alanine content. The results are shown in Table 3. Ion exchange column #2, using 0.15% industrial-grade ammonium chloride solution as the washing solution, showed good impurity removal effects for glutamic acid, lysine, and alanine. At 1h, the peak of impurity removal occurred, with some impurities still not completely removed. At 1.5h, the impurity content began to decrease, indicating that impurity replacement was complete. Therefore, 1.5h of washing achieved the optimal impurity removal effect for glutamic acid, lysine, and alanine.

[0039] Table 3

[0040] 0.5h 0 0.27 0.17 0.12 1h 0 0.4 0.26 0.19 1.5h 0 0.06 0.09 0.05

[0041] In this embodiment, ion exchange column #3 was used for washing. The L-arginine washing solution was collected at 0.5h, 1h, and 1.5h for the determination of arginine, glutamic acid, lysine, and alanine content. The results are shown in Table 4. Ion exchange column #3, using 0.3% industrial-grade ammonium chloride solution as the washing liquid, showed good removal efficiency for glutamic acid, lysine, and alanine. However, while removing glutamic acid, lysine, and alanine, ion exchange column #3 also showed some removal efficiency for L-arginine, indicating that ion exchange column #3 affects the yield of L-arginine.

[0042] Table 4

[0043]

[0044]

[0045] In this embodiment, three sets of ion exchange columns (1#, 2#, and 3#) were used for washing for 1.5 hours, and the conductivity and transmittance of the obtained L-arginine washing solution were measured. The results are shown in Table 5. The L-arginine washing solutions obtained using ion exchange columns 2# and 3# had lower transmittance and higher conductivity, and the difference between the two was not significant, indicating that ion exchange columns 2# and 3# were both effective in removing calcium and magnesium ions and pigments.

[0046] Table 5

[0047] 1# 0.4 78.5 2# 1.6 5.6 3# 1.9 4.5

[0048] In summary, by detecting the conductivity and transmittance of the L-arginine washing solution, it can be seen that all three ion exchange columns have good removal effects on calcium and magnesium ions and pigments. By detecting the content of arginine, glutamic acid, lysine and alanine in the L-arginine washing solution obtained after washing with the three ion exchange columns, it can be seen that the ion exchange column using 0.15% (2#) industrial grade ammonium chloride solution as washing solution has the best removal effect on glutamic acid, lysine and alanine when the washing time is 1.5h, and does not affect the yield of L-arginine.

[0049] Example 2:

[0050] S1: Filter the L-arginine fermentation broth through a ceramic membrane, collect the clear liquid from the ceramic membrane, and adjust the pH of the clear liquid from the ceramic membrane to 3-3.2;

[0051] S2: The pH-adjusted ceramic membrane solution from S1 is subjected to adsorption with a strong acid cation exchange resin at a flow rate of 0.6 BV. The adsorption process is as follows: the pH-adjusted ceramic membrane solution is fed into three sets (1#, 2#, and 3#) of ion exchange columns at a flow rate of 0.6 BV. The ion exchange columns are filled with strong acid cation exchange resin. The resin adsorption is considered saturated when the arginine content in the effluent reaches 30%-40% of the feed content. Then, purified water is introduced into the three sets of ion exchange columns at a flow rate of 1 BV, with a volume of 2 BV, to replace the remaining solution in the ion exchange columns.

[0052] S3: Prepare washing solutions, which are industrial-grade ammonium chloride solutions of 0%, 0.15%, and 0.3% respectively. Control the temperature of the washing solutions to be the same as that of the strongly acidic cation exchange resin in S2. Add the washing solutions to the strongly acidic cation exchange resin in S2 at a flow rate of 1 BV for washing. The washing time is 1.5 h for each of the three washing solutions, and L-arginine washing solutions are obtained.

[0053] S4: The L-arginine washing solution obtained in S3 was subjected to strong acid cation exchange resin analysis using 5.5% ammonia water at a flow rate of 0.6 BV, with an ammonia water volume of 2.5 BV, to obtain the high-flow fraction of ion-exchanged L-arginine.

[0054] Effect Experiment:

[0055] In this embodiment, the high flow rates of L-arginine obtained from the three ion exchange columns were tested for relevant indicators. The results are shown in Table 6. The test results of each indicator of ion exchange column #2 and ion exchange column #3 were relatively similar, and the difference in output quality was not significant. However, the output quality of ion exchange column #1 was poor.

[0056] Table 6

[0057] 1# 80.3 19.5 3915 4.5 2# 91.3 83.1 2630 2.1 3# 90.1 85.4 2540 1.9

[0058] Example 3:

[0059] S1: Filter the L-arginine fermentation broth through a ceramic membrane, collect the clear liquid from the ceramic membrane, and adjust the pH of the clear liquid from the ceramic membrane to 3-3.2;

[0060] S2: The pH-adjusted ceramic membrane solution from S1 is subjected to adsorption with a strong acid cation exchange resin at a flow rate of 0.6 BV. The adsorption process is as follows: the pH-adjusted ceramic membrane solution is fed into three sets (1#, 2#, and 3#) of ion exchange columns at a flow rate of 0.6 BV. The ion exchange columns are filled with strong acid cation exchange resin. The resin adsorption is considered saturated when the arginine content in the effluent reaches 30%-40% of the feed content. Then, purified water is introduced into the three sets of ion exchange columns at a flow rate of 1 BV, with a volume of 2 BV, to replace the remaining solution in the ion exchange columns.

[0061] S3: Prepare washing solutions, which are industrial-grade ammonium chloride solutions of 0%, 0.15%, and 0.3% respectively. Control the temperature of the washing solutions to be the same as that of the strongly acidic cation exchange resin in S2. Add the washing solutions to the strongly acidic cation exchange resin in S2 at a flow rate of 1 BV for washing. The washing time is 1.5 h for each of the three washing solutions, and L-arginine washing solutions are obtained.

[0062] S4: The L-arginine washing solution obtained in S3 was subjected to strong acid cation exchange resin analysis using 5.5% ammonia water at a flow rate of 0.6 BV, with an ammonia water volume of 2.5 BV, to obtain the high-flow fraction of ion-exchanged L-arginine.

[0063] S5: The high-flow-rate L-arginine obtained in S4 is multi-effect evaporated to 10%-11% of the dry matter. The high-flow-rate L-arginine obtained after multi-effect evaporation is placed in a single-effect crystallizer and concentrated and crystallized to 550-600 g / L. The concentration and crystallization treatment temperature is 55℃ to obtain wet L-arginine crystals.

[0064] S6: The L-arginine wet crystals obtained in S5 were separated into solid and liquid phases using a filter bag centrifuge. The crystals were washed with pure water at a volume of 5% and then dried using a fluidized bed to obtain the purified L-arginine dry product.

[0065] Effect Experiment:

[0066] In this embodiment, the quality of the dried L-arginine product obtained above was tested according to the national standard GB36897-2018 feed grade requirements. The results are shown in Table 7. The dried L-arginine products obtained by ion exchange column #2 and ion exchange column #3 both meet the national standard GB36897-2018 feed grade standard.

[0067] Table 7

[0068]

[0069] In this embodiment, the yield of the dried L-arginine product obtained above was tested, and the results are shown in Table 8. The dried L-arginine product obtained by ion exchange column #2 had the highest yield, reaching 86.7%, which is 10.6% higher than the yield of the dried L-arginine product obtained by ion exchange column #1, which uses water as the washing liquid.

[0070] Table 8

[0071] 1# 77.5％ 2# 86.7％ 3# 85.3％

[0072] In summary, the L-arginine ion exchange purification method provided by this invention has the best purification effect on glutamic acid, lysine, alanine, calcium and magnesium ions, and pigments when using 0.15% industrial-grade ammonium chloride solution as the washing liquid and washing time of 1.5 hours. The resulting dried L-arginine product has the best quality and yield.

[0073] The contents not described in detail in this specification are well-known to those skilled in the art. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for removing impurities from L-arginine via ion exchange, characterized in that, The impurity removal method includes the following steps: S1: Filter the L-arginine fermentation broth through a ceramic membrane, collect the clear liquid from the ceramic membrane, and adjust the pH of the clear liquid to 3-3.

5. S2: The clear liquid from the ceramic membrane after pH adjustment in S1 is adsorbed onto a strongly acidic cation exchange resin at a flow rate of 0.5-0.7 BV. The steps of the strongly acidic cation exchange resin adsorption are as follows: the clear liquid from the ceramic membrane after pH adjustment is fed onto an ion exchange column at a flow rate of 0.5-0.7 BV, the column is filled with strongly acidic cation exchange resin, and the resin adsorption is considered saturated when the arginine content in the effluent after exchange reaches 30%-40% of the feed content. S3: Prepare a washing solution. Control the temperature of the washing solution to be the same as that of the strongly acidic cation exchange resin in S2. Add the washing solution to the strongly acidic cation exchange resin in S2 at a certain flow rate to wash and obtain L-arginine washing solution. The washing solution is a 0.15% industrial grade ammonium chloride solution, the flow rate is 1 BV, and the washing time is 1.5 h. S4: The L-arginine washing solution obtained in S3 is subjected to a strong acid cation exchange resin analysis using ammonia water at a certain flow rate to obtain a high-flow fraction of ion-exchanged L-arginine; the ammonia water concentration is 5-6%, and the flow rate is 0.5-0.7 BV. S5: The high-flow-rate L-arginine obtained in S4 is subjected to multi-effect evaporation and then discharged, concentrated and crystallized to obtain wet L-arginine crystals. S6: The wet L-arginine crystals obtained in S5 are centrifuged and dried to obtain L-arginine after impurity removal.

2. The impurity removal method according to claim 1, characterized in that, The standard for ending the multi-effect evaporation process described in S5 is that the multi-effect evaporation reaches 10%-11% of the dry matter.

3. The impurity removal method according to claim 1, characterized in that, The concentration and crystallization process described in S5 involves placing the high-flow fraction after multi-effect evaporation into a single-effect crystallizer for concentration and crystallization to 550-600 g / L, with the concentration and crystallization temperature being 50-60℃.

4. The impurity removal method according to claim 1, characterized in that, The centrifugation process described in S6 involves solid-liquid separation using a bag filter centrifuge, followed by washing with pure water at a rate of 5% of the wet crystal volume.

5. The impurity removal method according to claim 1, characterized in that, The drying process described in S6 is performed using either a fluidized bed or a double cone apparatus.

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