A method for treating a glychocholic acid production mother liquor

Abstract

This invention discloses a method for treating mother liquor from glucuronolactone production, comprising: vacuum concentration, cooling crystallization, and filtration to obtain crude glucuronolactone and crude mother liquor; adding potassium hydroxide to the crude mother liquor for decolorization, followed by vacuum concentration to obtain a concentrated solution; and cooling crystallization of the concentrated solution to obtain potassium dihydrogen phosphate crystals. This invention targets the high-phosphate content mother liquor obtained from the enzymatic production of glucuronolactone using inositol as a raw material. First, crude glucuronolactone is recovered through a first cooling crystallization process, followed by the addition of potassium hydroxide and a second cooling crystallization process to obtain the high-value product, potassium dihydrogen phosphate. This invention not only achieves the recovery of glucuronolactone from the mother liquor, improving the production yield of glucuronolactone, but also transforms the phosphoric acid in the mother liquor into a valuable product, preparing high-value potassium dihydrogen phosphate, filling a technological gap in mother liquor treatment.

Description

Technical Field

[0001] This invention relates to the field of production tail liquor recycling technology, and in particular to a method for treating mother liquor from glucuronolactone production. Background Technology

[0002] Glucuronolactone, also known as Hepatoprotective Agent or Glucuronolactone, has the English name [D(+)-Glucofuranurono-6,3-lactone], molecular formula C6H8O6, and molecular weight 176.12. It is a white crystalline or crystalline powder, odorless, with a slightly bitter taste. Upon exposure to light, its color gradually darkens. When dissolved in water, a portion of the lactone is converted to glucuronic acid, reaching an equilibrium state and exhibiting an acidic reaction. Glucuronic acid is one of the important detoxification substances in the body. It can bind with carboxyl-containing toxins and drugs in the liver or intestines to form non-toxic or low-toxic glucuronic acid conjugates, which are then excreted in the urine. It can also reduce the activity of hepatic amylase, inhibit glycogenolysis, increase liver glycogen, and reduce fat storage, thus protecting the liver and playing a detoxification role.

[0003] There are two main methods for preparing glucuronolactone in the existing technology. One method is the nitric acid oxidation method using starch as raw material. The mother liquor produced by this method contains about 50% starch sugar, about 20% water, about 15% acetic acid, about 10% ethanol and a small amount of ethyl acetate, which causes serious pollution. The existing mother liquor treatment measures are to first concentrate the glucuronolactone mother liquor, distill off the mixture of ester, acetic acid and ethanol, and then directly neutralize the remaining residue to neutral pH for discharge or use it to produce oxalic acid. The mixture is then neutralized to pH 5-7 by adding soda ash or liquid alkali, heated and distilled to produce dilute ethanol. The residue is cooled and crystallized to form sodium acetate. The dilute ethanol is then purified by distillation in a distillation column to obtain high-content ethanol.

[0004] Another method is an enzyme-catalyzed method using inositol as a raw material. The inositol solution reacts under the catalysis of inositol oxidase to obtain glucuronic acid, which is then esterified with concentrated phosphoric acid and crystallized to obtain glucuronolactone. The mother liquor obtained by this method contains about 40% phosphoric acid, about 50% water, and about 10% glucuronolactone. There is currently no record in the art of how to treat the mother liquor of glucuronolactone production obtained by this method.

[0005] Therefore, there is an urgent need to establish a treatment method for the production mother liquor containing high phosphoric acid obtained by enzyme catalysis of inositol as a raw material, to fill the technological gap in this field. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a method for treating mother liquor from glucuronolactone production, which fills the technological gap in the treatment process of mother liquor containing high phosphoric acid obtained by enzyme catalysis of inositol as raw material.

[0007] To achieve the above objectives, the present invention provides the following technical solution: The present invention provides a method for processing mother liquor from glucuronolactone production, comprising the following steps:

[0008] The production mother liquor is concentrated by a first vacuum concentration to obtain concentrated mother liquor;

[0009] The concentrated mother liquor was subjected to a first cooling crystallization process. When the temperature dropped to 5-15℃, it was then filtered first to obtain crude glucuronolactone and crude mother liquor.

[0010] Dilute the crude mother liquor with water, add potassium hydroxide to adjust the pH to 3.0-3.5, and perform decolorization treatment to obtain a decolorized solution;

[0011] The decolorizing solution was concentrated under a second vacuum to obtain a potassium dihydrogen phosphate concentrate.

[0012] The potassium dihydrogen phosphate concentrate is subjected to a second cooling crystallization process. When the temperature drops to 5-20°C, potassium dihydrogen phosphate crystals are obtained through a second filtration process.

[0013] The present invention provides a method for treating the mother liquor from glucuronolactone production, comprising: vacuum concentration, cooling crystallization, and filtration to obtain crude glucuronolactone and crude mother liquor; adding potassium hydroxide to the crude mother liquor for decolorization, followed by vacuum concentration to obtain a concentrated solution; and cooling crystallization of the concentrated solution to obtain potassium dihydrogen phosphate crystals. This invention targets the high-phosphate content mother liquor obtained from the enzymatic production of glucuronolactone using inositol as a raw material. First, crude glucuronolactone is recovered through a first cooling crystallization process. Then, potassium hydroxide is added and subjected to a second cooling crystallization process. Since the original mother liquor has a high phosphoric acid content, the addition of potassium hydroxide reacts with the phosphoric acid to generate potassium dihydrogen phosphate. Concentration followed by cooling precipitates potassium dihydrogen phosphate crystals, yielding the high-value product potassium dihydrogen phosphate. This invention not only achieves the recovery of glucuronolactone from the mother liquor, improving the production yield of glucuronolactone, but also reuses the phosphoric acid in the mother liquor, turning waste into treasure, and preparing the high-value potassium dihydrogen phosphate product, filling a technological gap in mother liquor treatment. Detailed Implementation

[0014] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only for explaining the present invention and are not intended to limit the present invention.

[0015] This invention provides a method for treating mother liquor from glucuronolactone production, comprising the following steps:

[0016] The production mother liquor is concentrated by a first vacuum concentration to obtain concentrated mother liquor;

[0017] The concentrated mother liquor was subjected to a first cooling crystallization process. When the temperature dropped to 5-15℃, it was then filtered first to obtain crude glucuronolactone and crude mother liquor.

[0018] Dilute the crude mother liquor with water, add potassium hydroxide to adjust the pH to 3.0-3.5, and perform decolorization treatment to obtain a decolorized solution;

[0019] The decolorizing solution was concentrated under a second vacuum to obtain a potassium dihydrogen phosphate concentrate.

[0020] The potassium dihydrogen phosphate concentrate is subjected to a second cooling crystallization process. When the temperature drops to 5-20°C, potassium dihydrogen phosphate crystals are obtained through a second filtration process.

[0021] This invention first concentrates the production mother liquor under vacuum to obtain a concentrated mother liquor. In this invention, the production mother liquor is obtained from the enzymatic production of glucuronide using inositol as a raw material. Specifically, it includes: preparing a 10-100 g / L inositol solution, adding whole cells containing inositol oxidase to achieve a bacterial concentration of 30 OD, and carrying out a conversion reaction at a temperature of 30-40℃ and a reaction pH of 8.0-9.0 to obtain a glucuronic acid conversion solution. This conversion solution is then concentrated to obtain a glucuronic acid concentrate with a solid content of 50-70 wt%. A concentrated phosphoric acid solution (70-85% by mass) with a solid content of 10-50% is added to the concentrate, and the reaction is carried out for 1-2 hours to obtain glucuronide and the production mother liquor. Further, the process of preparing the glucuronic acid solution using the inositol solution as a raw material can be referred to in reference CN109423469A. The mother liquor obtained above for the production of glucuronolactone consists of approximately 40% phosphoric acid, approximately 50% water, approximately 10% glucuronolactone, and approximately 1% other substances. Based on the composition of the mother liquor, it is clear that the main challenges in its treatment lie in the recovery of glucuronolactone and the processing of phosphoric acid.

[0022] In this invention, the preferred conditions for the first vacuum concentration are: temperature 55-70℃ and vacuum degree ≤ -0.09MPa; more preferably, the concentration is 60-65℃ and the vacuum concentration is -0.095MPa to -0.09MPa. This invention does not impose special requirements on the vacuum concentration equipment; for example, a rotary evaporator can be used. In this invention, the solid content of the concentrated mother liquor is preferably 50-70wt%.

[0023] After obtaining the concentrated mother liquor, the present invention subjectes the concentrated mother liquor to a first cooling crystallization. When the temperature drops to 5-15°C, it is then filtered to obtain crude glucuronolactone and crude mother liquor. In the present invention, the cooling rate in the first cooling crystallization is preferably 5-10°C / h, and the stirring rate is preferably 30-200 rpm. The present invention does not have special requirements for the equipment used for the cooling crystallization; for example, a crystallization kettle can be used. In the present invention, the first filtration is preferably performed using filter paper filtration or vacuum filtration. When using filter paper filtration, industrial filter paper can be used, and the pore size of the filter paper is preferably 5-10 μm. When using vacuum filtration, a 5-10 μm sintered sand funnel can be used. Furthermore, in the present invention, a vacuum pump or centrifuge can also be used for filtration.

[0024] This invention also includes washing the obtained crude glucuronolactone, comprising: washing the crude glucuronolactone in anhydrous ethanol, and then vacuum drying to obtain purified glucuronolactone; wherein, the preferred ratio of crude glucuronolactone to anhydrous ethanol is 1:(0.8-1.5)(w / v); the preferred vacuum drying conditions are: temperature 50-80℃, vacuum degree ≤-0.09MPa; this invention does not have special requirements for the vacuum drying equipment, for example, a vacuum drying oven can be used. The purified glucuronolactone obtained by washing according to this invention can achieve a purity of over 96%.

[0025] After obtaining the crude mother liquor, this invention dilutes the crude mother liquor with water, adds potassium hydroxide to adjust the pH to 3.0-3.5, and performs decolorization treatment to obtain a decolorized solution. In this invention, the volume ratio of the crude mother liquor to water is preferably 1:(0.5-1.5), more preferably 1:1. This invention also includes stirring during the dilution of the crude mother liquor with water. This invention does not have a particular limitation on the stirring rate of the stirring process, as long as the crude mother liquor is diluted evenly. In this invention, the potassium hydroxide is preferably solid potassium hydroxide. After adding potassium hydroxide to adjust the pH, this invention also includes a stirring reaction, wherein the stirring speed is preferably 30-200 rpm, and the stirring time is preferably 1-2 hours. The purpose of the stirring reaction is to ensure that the reaction proceeds fully and potassium dihydrogen phosphate is generated. In this invention, the decolorization treatment is preferably carried out using activated carbon or resin. When activated carbon is used, the amount of activated carbon is preferably 1-5% of the mass of the reaction solution, and the pore size of the activated carbon is preferably 10 μm. When resin is used, the amount of resin is preferably 0.3-0.5 BV of the reaction solution volume, and the flow rate is preferably 1-4 BV / h. This invention does not have any special restrictions on the type of resin, and common decolorizing resins can be selected, such as LS108 resin. The decolorization time is preferably 20-60 min. This invention does not have any special requirements on the source of activated carbon, and commercially available products can be used.

[0026] After obtaining the decolorized solution, the present invention further concentrates the decolorized solution under a second vacuum to obtain a potassium dihydrogen phosphate concentrate. In the present invention, the preferred conditions for the second vacuum concentration are: temperature 55-70℃ and vacuum degree ≤ -0.09MPa; more preferably, the concentration is 60-65℃ and the vacuum concentration is -0.095MPa to -0.09MPa. The present invention does not have special requirements for the vacuum concentration equipment; for example, a rotary evaporator can be used. In the present invention, the preferred concentration of the potassium dihydrogen phosphate concentrate is 30-35 Baume.

[0027] After obtaining a concentrated potassium dihydrogen phosphate solution, the present invention subjectes the concentrated solution to a second cooling crystallization process. When the temperature drops to 5-20°C, the solution is then filtered a second time to obtain potassium dihydrogen phosphate crystals. In this invention, the cooling rate during the second cooling crystallization is preferably 2-8°C / h, and the stirring rate is preferably 30-100 rpm. The present invention does not impose special requirements on the equipment used for the cooling crystallization; for example, a crystallization kettle can be used. In this invention, the first filtration preferably employs filter paper filtration or vacuum filtration. When using filter paper filtration, industrial filter paper can be used, and the pore size of the filter paper is preferably 5-10 μm. When using vacuum filtration, a 5-10 μm sintered sand funnel can be used. Furthermore, in this invention, a vacuum pump or centrifuge can also be used for filtration.

[0028] The potassium dihydrogen phosphate crystals obtained by filtration are wet crystals. The present invention further includes: vacuum drying the wet crystals to obtain white potassium dihydrogen phosphate crystals; wherein, the vacuum drying conditions are preferably: temperature 50-80℃, vacuum degree ≤-0.09MPa.

[0029] To better illustrate the technical solution of the present invention, the following specific embodiments are also provided. It should be understood that, unless otherwise specified, all raw materials used in the following embodiments are commercially available.

[0030] Table 1 below lists the main components of three batches of glucuronolactone production mother liquor, all of which were provided by Zhucheng Haotian Pharmaceutical Co., Ltd.

[0031] Table 1. Composition of mother liquor in glucuronolactone production

[0032]

[0033]

[0034] Example 1

[0035] S1. Take 2L of mother liquor from the production of glucuronolactone in batch 1, and concentrate it under vacuum at 70℃ and -0.09MPa to obtain 0.8L of concentrated mother liquor with a solid content of 65%.

[0036] S2. The concentrated mother liquor was stirred and cooled to crystallize at a rate of 8℃ / h. The stirring speed was 80 rpm. When the temperature dropped to 10℃, it was filtered through 8 μm filter paper to obtain 193 g crude glucuronolactone and 0.6 L crude mother liquor.

[0037] S3. 193g of crude glucuronolactone was washed with 200ml of anhydrous ethanol and dried under vacuum at 65℃ and -0.09MPa to obtain 184g of white crystals. Liquid chromatography analysis showed that the glucuronolactone content in the white crystals was 96.1%.

[0038] S4.0.6L of crude mother liquor was diluted with 0.6L of water, stirred evenly, and then 381g of solid potassium hydroxide was added to adjust the pH to 3.18. Then 15g of activated carbon was added for decolorization for 30min to obtain 1.5L of decolorized solution.

[0039] S5. The decolorizing solution was concentrated to 34 Baume under the conditions of 70℃ and vacuum degree -0.09MPa, and then cooled and crystallized by stirring at a rate of 8℃ / h. The stirring speed was 80rpm. When the temperature dropped to 20℃, 455g of wet potassium dihydrogen phosphate crystals were obtained by filtration through 6um filter paper.

[0040] S6. The wet potassium dihydrogen phosphate crystals were vacuum dried at 65℃ and -0.09MPa to obtain 415g of white potassium dihydrogen phosphate crystals. The potassium dihydrogen phosphate content was determined to be 99.5%.

[0041] Example 2

[0042] S1. Take 2L of mother liquor from batch 2 of glucuronolactone production and concentrate it under vacuum at 55℃ and -0.095MPa to obtain 1L of concentrated mother liquor with a solid content of 50%.

[0043] S2. The concentrated mother liquor was stirred and cooled to crystallize at a rate of 5℃ / h. The stirring speed was 30 rpm. When the temperature dropped to 5℃, it was filtered through a 10 μm sand core funnel to obtain 205 g of crude glucuronolactone and 0.8 L of crude mother liquor.

[0044] S3. 205g of crude glucuronolactone was washed with 307.5ml of anhydrous ethanol and dried under vacuum at 50℃ and -0.095MPa to obtain 198g of white crystals. Liquid chromatography analysis showed that the glucuronolactone content in the white crystals was 96.8%.

[0045] S4.0.8L of crude mother liquor was diluted with 0.4L of water, stirred evenly, and then 362g of solid potassium hydroxide was added to adjust the pH to 3.0. The mixture was reacted at 150rpm for 1.5h, and then 20g of activated carbon was added for decolorization for 20min to obtain 1.5L of decolorized solution.

[0046] S5. The decolorizing solution was concentrated to 30 Baume under the conditions of 55℃ and vacuum degree -0.095MPa, and then cooled and crystallized by stirring at a rate of 5℃ / h and a stirring speed of 30rpm. When the temperature dropped to 10℃, 432g of wet potassium dihydrogen phosphate crystals were obtained by filtration through 5um filter paper.

[0047] S6. The wet potassium dihydrogen phosphate crystals were vacuum dried at 80℃ and -0.10MPa to obtain 410g of white potassium dihydrogen phosphate crystals. The potassium dihydrogen phosphate content was determined to be 99.6%.

[0048] Example 3

[0049] S1. Take 2L of mother liquor from the production of glucuronolactone in batch 3, and concentrate it under vacuum at 60℃ and -0.10MPa to obtain 0.75L of concentrated mother liquor with a solid content of 70%.

[0050] S2. The concentrated mother liquor was stirred and cooled to crystallize at a rate of 10℃ / h. The stirring speed was 200rpm. When the temperature dropped to 15℃, it was filtered through 10um filter paper to obtain 173g of crude glucuronolactone and 0.6L of crude mother liquor.

[0051] S3. 173g of crude glucuronolactone was washed with 138.4ml of anhydrous ethanol and dried under vacuum at 80℃ and -0.10MPa to obtain 168g of white crystals. Liquid chromatography analysis showed that the glucuronolactone content in the white crystals was 97.2%.

[0052] S4.0.6L of crude mother liquor was diluted with 0.9L of water, stirred evenly, and then 406g of solid potassium hydroxide was added to adjust the pH to 3.5. The reaction was carried out at 200rpm for 1h, and then decolorized for 60min through 500ml of LS108 resin at a flow rate of 2BV / h to obtain 1.8L of decolorized solution.

[0053] S5. The decolorizing solution was concentrated to 35 Baume under the conditions of 60℃ and vacuum degree -0.10MPa, and then cooled and crystallized by stirring at a rate of 2℃ / h. The stirring speed was 100rpm. When the temperature dropped to 5℃, 479g of wet potassium dihydrogen phosphate crystals were obtained by filtration through a 10um sand core funnel.

[0054] S6. The wet potassium dihydrogen phosphate crystals were vacuum dried at 50℃ and -0.095MPa to obtain 455g of white potassium dihydrogen phosphate crystals. The potassium dihydrogen phosphate content was determined to be 99.6%.

[0055] Comparative Example 1

[0056] Compared with Example 1, this comparative example adjusts the cooling rate in step S2 to 15℃ / h, while keeping other conditions unchanged.

[0057] Comparative Example 2

[0058] Compared with Example 2, this comparative example adjusts the cooling rate in step S5 to 15℃ / h, while keeping other conditions unchanged.

[0059] Comparative Example 3

[0060] Compared with Example 3, this comparative example changes "adjust pH to 3.18" in step S4 to "adjust pH to 4", while keeping other conditions unchanged.

[0061] Table 2 below lists the purity and potassium dihydrogen phosphate content of the purified glucuronolactone obtained in the examples and comparative examples.

[0062] Table 2. Purity of glucuronolactone and potassium dihydrogen phosphate content in the examples and comparative examples.

[0063]

[0064] Test case

[0065] A. Glucuronolactone Liquid Chromatography Method:

[0066] Mobile phase: 10 mmol / L formic acid aqueous solution;

[0067] Chromatographic column: Calcium column (300*7.7 or similar column);

[0068] Flow rate: 0.5 mL / min;

[0069] Column temperature: 55℃;

[0070] Detector temperature: 45℃;

[0071] Standard concentration: 1.0 mg / mL; the standard was selected from the National Institutes for Food and Drug Control, D-glucuronide, CAS number 32449-92-6, with a content of 99.9% as C6H8O6;

[0072] Test sample concentration: 1.0 mg / mL;

[0073] Chromatographic conditions: run for 30 min with 100% aqueous formic acid at a concentration of 10 mmol / L.

[0074] B. Determination method of potassium dihydrogen phosphate content: According to the national standard GB / T 1274-2011 for potassium dihydrogen phosphate.

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for treating a glycol lactone production mother liquor, characterized by, Includes the following steps: The production mother liquor is concentrated by a first vacuum concentration to obtain concentrated mother liquor; The concentrated mother liquor was subjected to a first cooling crystallization process. When the temperature dropped to 5-15℃, it was then filtered first to obtain crude glucuronolactone and crude mother liquor. Dilute the crude mother liquor with water, add potassium hydroxide to adjust the pH to 3.0-3.5, and perform decolorization treatment to obtain a decolorized solution; The decolorizing solution was concentrated under a second vacuum to obtain a potassium dihydrogen phosphate concentrate. The potassium dihydrogen phosphate concentrate was subjected to a second cooling crystallization process. When the temperature was reduced to 5-20°C, potassium dihydrogen phosphate crystals were obtained by a second filtration process. The cooling rate in the first cooling crystallization is 5-10℃ / h, and the stirring rate is 30-200rpm. The cooling rate in the second cooling crystallization is 2-8℃ / h, and the stirring rate is 30-100rpm.

2. The method of claim 1, wherein, The conditions for the first vacuum concentration are: temperature 55-70℃, vacuum degree ≤-0.09MPa.

3. The method of claim 1, wherein, The solid content of the concentrated mother liquor is 50-70 wt%.

4. The method according to claim 1, characterized in that, The first filtration employs filter paper filtration or vacuum filtration; and / or, The filter paper has a pore size of 5-10 μm during filtration; and / or, The filtration process uses a 5-10µm sand core funnel.

5. The method according to claim 1, characterized in that, The volume ratio of the crude mother liquor to water is 1:(0.5-1.5); and / or, the decolorization is performed using activated carbon or resin; and / or, the amount of activated carbon used is 1-5% of the mass of the reaction solution, and the amount of resin used is 0.3-0.5 BV of the reaction solution volume.

6. The method according to claim 1, characterized in that, The conditions for the second vacuum concentration are: temperature 55-70℃, vacuum degree ≤-0.09MPa.

7. The method according to claim 1, characterized in that, The concentration of the potassium dihydrogen phosphate concentrate is 30-35 Baume.

8. The method according to claim 1, characterized in that, The second filtration uses filter paper filtration or vacuum filtration; and / or, the filter paper pore size is 5-10 μm when using filter paper filtration; and / or, the vacuum filtration uses a 5-10 μm sand core funnel.

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