A method for removing organic acids from fermented vitamin B5

Abstract

The application discloses a method for removing organic acid in fermented vitamin B5, comprising the following steps: (1) treating D-pantothenate ammonium fermentation liquor through a ceramic membrane, an ultrafiltration membrane and a cation resin to obtain a D-pantothenate solution; (2) treating the D-pantothenate solution through an anion resin column to obtain an anion column liquid from which organic acid is removed; and the resin filled in the anion resin column is a weak base anion exchange resin with an acrylic acid skeleton. The method can effectively remove the organic acid generated in the process of synthesizing vitamin B5 by a biological fermentation method, can improve the yield and purity of a final product, and is more beneficial to the crystallization of vitamin B5.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of vitamin B5 preparation, and particularly relates to a method for removing organic acids in fermented vitamin B5. BACKGROUND

[0002] Vitamin B5, also known as pantothenic acid, is a water-soluble vitamin with a chemical formula of C9H 17 NO5. Vitamin B5 can be used as a color aid in the food industry, and 0.01-0.022 g per kg of meat can make the meat color good. It is also used as a food fortifier in bread, cakes, dairy products. In the feed industry, it is used as a vitamin additive added to the feed of poultry, pigs, young ruminants, fish, etc. In cosmetics, it plays a role in protecting and improving rough skin.

[0003] The existing synthesis methods of vitamin B5 include chemical synthesis and microbial fermentation, wherein the microbial fermentation method has the advantages of mild conditions, environmental friendliness, and direct formation of the required stereoisomer, and has important application prospects.

[0004] The fermentation broth obtained by the fermentation method of vitamin is generally obtained by filtering, resin treatment and crystallization to obtain vitamin B5 or a corresponding salt. For example, the Chinese patent application with the publication number CN1225358A discloses a production method of D-pantothenic acid. The fermentation broth is first filtered, then flows through a cation exchange resin column to remove cations, and then flows through an anion exchange resin to remove organic acids, and then subsequent crystallization operation is performed to obtain a salt of D-pantothenic acid.

[0005] The present inventors found that the existing technology has the defects of low removal rate of organic acids (the organic acids mentioned below refer to other organic acids except D-pantothenic acid), low treatment efficiency, and large loss of D-pantothenic acid when the fermentation broth obtained by the fermentation method is treated by resin. In particular, it is difficult to selectively remove organic acids while retaining D-pantothenic acid, which affects the cost of the entire fermentation production of vitamin B5, and there is a great need for improvement of this step. SUMMARY

[0006] The present application provides a method for removing organic acids in fermented vitamin B5, which can effectively remove the organic acids produced in the process of synthesizing vitamin B5 by biological fermentation method, while reducing the loss of D-pantothenic acid in the purification process, and has a high treatment rate.

[0007] The technical scheme of the present application is as follows:

[0008] A method for removing organic acids in fermented vitamin B5, comprising:

[0009] (1) D-pantothenic acid ammonium fermentation broth is filtered and acidified to obtain a D-pantothenic acid solution;

[0010] (2) The D-pantoic acid solution is treated by an anion resin column to obtain an anion column liquid from which organic acids are removed, i.e. the purified D-pantoic acid solution;

[0011] The resin filled in the anion resin column is D319 exchange resin.

[0012] The present inventors have found that when a specific D319 exchange resin is used for treatment, the organic acids in the D-pantoic acid solution can be effectively removed while avoiding loss of D-pantoic acid, so that the concentration of hydrogen ions: the concentration of pantoic acid ≤ 1.15:1, and the treatment capacity per unit time is larger when D319 exchange resin is used, and the treatment yield is high.

[0013] In step (1), the filtration is performed in sequence using ceramic membranes and ultrafiltration membranes; and the acidification is performed using a cation resin.

[0014] The ceramic membranes and ultrafiltration membranes can remove solid particles and macromolecular impurities in the fermentation broth, and then the cation resin can convert the organic acid salts and D-pantoic acid ammonium into organic acids and D-pantoic acid through ion exchange. The type of cation resin is not particularly strictly required, and a strong acid cation resin can be generally selected, for example, the type of strong acid cation resin can be selected to be 732 type, JK008 type or JK006 type resin, etc., as long as the corresponding salt can be fully converted into acid.

[0015] The D-pantoic acid solution after filtration and acidification contains various organic acids, including but not limited to acetic acid, succinic acid, citric acid, oxalacetic acid, pyruvic acid, etc. As preferred, in step (2), the ratio of the total hydrogen ion concentration to D-pantoic acid in the D-pantoic acid solution before treatment is 2-4:1, i.e. the molar ratio of organic acids to D-pantoic acid is 1-3:1, at which time the method of the present application can be better for treatment.

[0016] As preferred, in step (2), the exchange capacity of the D319 exchange resin is 2.5-3.0 mol / L.

[0017] As preferred, in step (2), the anion resin column is formed by connecting A and B columns in series.

[0018] The D-pantoic acid solution is fed from the A column, and the treated liquid is collected from the B column. Using this series connection mode, the treatment efficiency of the impurity acid can be more effectively improved.

[0019] As preferred, in step (2), the anion resin column is activated and regenerated by using alkali activation, water washing with alkali, acid activation, water washing with acid, secondary alkali activation and secondary water washing with alkali before use, so that the anion resin column can achieve the best treatment state.

[0020] Further, the alkali used in the alkali activation is 1-5wt% NaOH aqueous solution, the amount is 2-4BV, and the amount of deionized water in the alkali washing is 5-10BV;

[0021] The acid used in the acid activation is 5-10wt% hydrochloric acid solution, the amount is 1-3BV, and the amount of deionized water in the acid washing is 2-4BV;

[0022] The alkali used in the secondary alkali activation is 1-5wt% NaOH aqueous solution, the amount is 2-4BV, and the amount of secondary alkali washing is 5-10BV;

[0023] The flow rate of the activated regeneration is 1-5BV / h. As preferred, in step (2), the flow rate of the D-pantothenic acid solution in the anion resin column is 2-8BV / h, and when the flow rate is up to 8BV / h, the removal efficiency is still good.

[0024] Compared with the prior art, the beneficial effects of the present application are embodied in:

[0025] (1) The D-pantothenic acid solution is treated by the D319 exchange resin of the present application, the organic acid generated in the process of synthesizing vitamin B5 is effectively removed, the loss of D-pantothenic acid is avoided, and the concentration of hydrogen ions in the treated solution is ≤1.15:1 of the concentration of D-pantothenic acid;

[0026] (2) When the D-pantothenic acid solution is treated by the D319 exchange resin of the present application, the treatment capacity per unit time is improved, and the treatment yield is higher. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 The figure is a schematic diagram of the chromatographic column of the present application. DETAILED DESCRIPTION

[0028] In the present application, the total hydrogen ion concentration and D-pantothenic acid ratio are molar ratios. For example, the hydrogen ion concentration of succinic acid is 2. The hydrogen ion concentration of a ternary acid is 3.

[0029] The general treatment process of the present application is as follows:

[0030] (1) The D-pantothenic acid ammonium fermentation liquor is treated by ceramic membranes, ultrafiltration membranes, and cation resins to obtain a D-pantothenic acid solution, and a large amount of organic acids exist in the solution, the molar ratio of the organic acids to D-pantothenic acid is 1-3:1, and these organic acids include but are not limited to acetic acid, succinic acid, citric acid, oxalacetic acid, and pyruvic acid;

[0031] (2) After the D-pantothenic acid solution treated by the cation resin is treated by the acrylic weak base resin, the molar ratio of the organic acids to D-pantothenic acid is reduced to 0-0.1:1, and the removal rate of the organic acids is more than 90%;

[0032] When using the resin for the first time, the resin activation process is as follows: alkali activation, water washing alkali, acid activation, water washing acid, alkali activation, and water washing alkali, with the following dosages: 3 BV 4wt% NaOH, 7 BV deionized water, 2 BV 7wt% HCl, 3 BV deionized water, 3 BV 4wt% NaOH, and 7 BV deionized water, respectively, at a flow rate of 2 BV / h (range 1-5 BV / h). After the anion column activation is completed, the D-pantothenic acid solution is fed through column A, and the qualified solution is collected through column B (the qualified solution is defined as having a hydrogen ion concentration of ≤1.15 and a pantothenic acid concentration of ≤1.15).

[0033] The optimal specific resin type is Suqing D319, with a resin exchange capacity of 2.7 mol / L, which is an acrylic skeleton weak base anion exchange resin.

[0034] Example 1

[0035] The D-pantothenic acid fermentation broth was treated with a ceramic membrane, an ultrafiltration membrane, and a strong acid cation exchange resin (type 732) to obtain 5000g of D-pantothenic acid solution with a D-pantothenic acid content of 60mg / g. The contents of acetic acid, succinic acid, citric acid, oxaloacetic acid, and pyruvic acid in the D-pantothenic acid solution were 0.063mol / kg, 0.054mol / kg, 0.085mol / kg, 0.038mol / kg, and 0.1377mol / kg, respectively, and the ratio of total hydrogen ion concentration to D-pantothenic acid concentration was 3.3:1. Figure 1 Connect the resin columns and fill each column with 500 mL of J-18 resin at a flow rate of 1 L / h. Regenerate the resin with 3000 mL of 4 wt% NaOH, 7000 mL of deionized water, 2000 mL of 7 wt% HCl, 3000 mL of deionized water, 3000 mL of 4 wt% NaOH, and 7000 mL of deionized water, respectively. After resin regeneration, 5000g of D-pantothenic acid solution was fed into column A at a flow rate of 1L / h. The solution with pH ≤ 4 was collected by column B, yielding 4500g of anion exchange solution. The D-pantothenic acid content was 59.5mg / g, and the contents of acetic acid, succinic acid, citric acid, oxaloacetic acid, and pyruvic acid were 0.005mol / kg, 0.054mol / kg, 0.012mol / kg, 0.011mol / kg, and 0.0439mol / kg, respectively. The ratio of total hydrogen ion concentration to D-pantothenic acid concentration was 1.8:1, and the D-pantothenic acid yield was 89.25%.

[0036] Examples 2-5

[0037] The resins were replaced with D301R, D301T, D318, and D301, while other parameters remained the same as in Example 1. The results are shown in Table 1.

[0038] Example 6

[0039] The D-pantoic acid ammonium fermentation broth was treated by ceramic membrane, ultrafiltration membrane and strong acid cation resin type 732 to obtain 5000 g of D-pantoic acid solution with a D-pantoic acid content of 60 mg / g. The contents of acetic acid, succinic acid, citric acid, oxalacetic acid and pyruvic acid in the D-pantoic acid solution were 0.063 mol / kg, 0.054 mol / kg, 0.085 mol / kg, 0.038 mol / kg and 0.1377 mol / kg, respectively. The ratio of total hydrogen ion concentration to D-pantoic acid concentration was 3.3:1. The D-pantoic acid solution was treated by the following steps: Figure 1 The resin columns were connected and each column was filled with 500 mL of D319 resin at a flow rate of 1 L / h. The resin was regenerated by using 3000 mL of 4 wt% NaOH, 7000 mL of deionized water, 2000 mL of 7 wt% HC1, 3000 mL of deionized water, 3000 mL of 4 wt% NaOH and 7000 mL of deionized water, respectively. After the regeneration of the resin, 4725 g of D-pantoic acid solution was fed into column A at a flow rate of 1 L / h. The effluent with a pH of less than 4 was collected from column B to obtain 4500 g of negative column effluent. The D-pantoic acid content was 60.5 mg / g. The contents of acetic acid, succinic acid, citric acid, oxalacetic acid and pyruvic acid were 0.0042 mol / kg, 0.002 mol / kg, 0.003 mol / kg, 0.0013 mol / kg and 0.0021 mol / kg, respectively. The ratio of total hydrogen ion concentration to D-pantoic acid concentration was 1.08:1. The D-pantoic acid yield was 96.03%.

[0040] Examples 7-9

[0041] The flow rate and treatment results under the conditions of Example 6 are shown in Table 1.

[0042] Table 1 Treatment conditions and results of Examples 1-9

[0043] Examples Resin model Flow rate / BV / h Total hydrogen ion concentration of the effluent: D-pantothenic acid concentration Yield 1 J-18 2 1.8:1 89.25％ 2 D301R 2 1.9:1 91.25％ 3 D301T 2 1.7:1 93.36％ 4 D318 2 1.8:1 85.85％ 5 D301 2 1.6:1 87.14％ 6 D319 2 1.08:1 96.03％ 7 D319 4 1.09:1 93.23％ 8 D319 6 1.11:1 92.35％ 9 D319 8 1.13:1 92.62％

[0044] The results show that, compared with other anion exchange resins, the use of D319 resin and the AB column series connection can obtain a D-pantoic acid material with a total hydrogen ion concentration:D-pantoic acid ratio of less than 1.15. At the same time, the treatment capacity can be as high as 8 BV / h and the yield can be as high as 96%.

Claims

1. A method for removing organic acids from a fermented vitamin B5, characterized in that, The method comprises the following steps: (1) obtaining a D-pantoic acid solution by filtering and acidifying a D-pantoic acid ammonium fermentation liquor; (2) treating the D-pantoic acid solution obtained in step (1) by an anion resin column to obtain an anion column liquid from which organic acids are removed; The resin filled in the anion resin column is D319 exchange resin; In step (2), the ratio of the total hydrogen ion concentration to D-pantoic acid in the D-pantoic acid solution before the treatment by the anion resin column is 2-4:1; In step (2), the organic acids contained in the D-pantoic acid solution before the treatment by the anion resin column include one or more of acetic acid, succinic acid, citric acid, oxalacetic acid and pyruvic acid; In step (2), the flow rate of the D-pantoic acid solution in the anion resin column is 2-8 BV / h.

2. The method of removing organic acids from fermented vitamin B5 according to claim 1, characterized in that, In step (1), the filtration is performed by ceramic membranes and ultrafiltration membranes in sequence; The acidification is performed by treatment with a cation resin.

3. The method of removing organic acids from fermented vitamin B5 according to claim 2, characterized in that, The cation resin is a strong acid cation resin.

4. The method of removing organic acids from fermented vitamin B5 according to claim 1, characterized by, In step (2), the exchange capacity of the D319 exchange resin is 2.5-3.0 mol / L.

5. The method of removing organic acids from fermented vitamin B5 according to claim 1, wherein, In step (2), the anion resin column is formed by connecting an A column and a B column in series; The D-pantoic acid solution is fed from the A column, and the treated liquid is collected from the B column.

6. The method of removing organic acids from fermented vitamin B5 according to claim 1, wherein, In step (2), the anion resin column is activated and regenerated by alkali activation, alkali washing, acid activation, acid washing, secondary alkali activation and secondary alkali washing before use.

7. The method of removing organic acids from fermentation vitamin B5 according to claim 6, wherein, The alkali used for the alkali activation is 1-5 wt% NaOH aqueous solution, and the amount used is 2-4 BV; the amount of deionized water used for the alkali washing is 5-10 BV; The acid used for the acid activation is 5-10 wt% hydrochloric acid solution, and the amount used is 1-3 BV; the amount of deionized water used for the acid washing is 2-4 BV; The alkali used for the secondary alkali activation is 1-5 wt% NaOH aqueous solution, and the amount used is 2-4 BV; the amount of the secondary alkali washing is 5-10 BV; The flow rate of the activation and regeneration is 1-5 BV / h.

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