A method for preparing glucuronolactone

Abstract

The present invention discloses a preparation method of glucurone, which relates to the technical field of esterification reactions. The method comprises the following steps: adding inositol oxidase to an inositol feed solution for conversion to obtain a conversion solution, and successively subjecting the conversion solution to filtration, ion exchange, decolorization, thermal concentration, and lactonization crystallization steps to obtain crude glucurone. The preparation method of the present invention uses inositol as a raw material, and after converting inositol into glucuronic acid solution under the action of an enzyme, adopts filtration, ion exchange, decolorization, thermal concentration, and lactonization crystallization steps to prepare crude glucurone. By adopting the technical solution of the present invention to prepare glucurone, the problems of low extraction rate of crude products, severe operating pressure, strict equipment requirements, and environmental pollution existing in the nitric acid oxidation method using starch as a raw material are solved. At the same time, the present invention uses inositol as a raw material, which is a new process different from the process using starch as a raw material, and has the advantages of low production cost, short cycle, and industrialization feasibility.

Description

Technical Field

[0001] The present invention relates to the technical field of esterification reactions, and particularly to a method for preparing glucuronolactone. Background Art

[0002] The full Chinese name of glucuronolactone is glucose glucuronic acid lactone, commonly known as hepatol. Its molecular formula is C6H8O6, and its chemical composition is D(+)-furan glucuronic acid γ-lactone. Its English name is [D(+)-Glucofuranurono-6,3-lactone]. As a liver detoxifying agent and immune function regulator, glucuronolactone is a conventional good medicine for protecting the liver. Glucuronolactone and its subsequent products are also the main additives in functional beverages and foods, weight loss drugs, cosmetics, etc., and have the effects of supplementing physical energy, improving hypoxia, nourishing the skin, and delaying aging.

[0003] In the prior art, the main method for producing glucuronolactone is the nitric acid oxidation method using starch as a raw material, including: adding starch to nitric acid with a content of about 80% (V / V) for oxidation to obtain a starch oxidation solution, heating and pressurizing the obtained starch oxidation solution for hydrolysis under acidic conditions to obtain a hydrolysis solution mainly composed of glucuronic acid. After the hydrolysis solution is concentrated under reduced pressure, a composite acid reagent composed of phosphoric acid and sulfuric acid or glacial acetic acid is added for an esterification reaction. After the esterification reaction is completed, ethanol is added for recrystallization to obtain a crude glucuronolactone product. In the above technical solution, the process of oxidizing starch with nitric acid to obtain a hydrolysis solution of glucuronic acid needs to be carried out in a high-pressure reaction kettle, and the pressure during the reaction in the kettle generally needs to be controlled at about 245.25 kPa (2.5 kgf / cm 2 ); there are problems such as low extraction rate of the crude product, strict requirements for equipment, and harsh operating pressure. At the same time, the nitric acid oxidation process will also cause relatively large pollution to the environment.

[0004] In addition, in the prior art, there is no disclosure of a related method for preparing glucuronolactone using inositol as a raw material. The present invention is a new process different from using starch as a raw material. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a method for preparing glucuronolactone to overcome the problems of harsh and complex preparation processes and low extraction rate of crude products in the prior art for preparing glucuronolactone.

[0006] To achieve the above purpose, the present invention provides the following technical solutions: The present invention provides a method for preparing glucuronolactone, including the following steps:

[0007] Adding inositol oxidase to an inositol feed liquid for conversion to obtain a conversion liquid;

[0008] Filtering the conversion liquid to obtain a filtrate,

[0009] The filtrate is desalted by ion exchange to obtain a desalted solution,

[0010] The desalted solution is decolorized to obtain a decolorized solution,

[0011] The decolorized solution is thermally concentrated to obtain a concentrated solution,

[0012] The concentrated solution is subjected to lactonization crystallization to obtain a crude product of glucuronolactone.

[0013] In the method for preparing glucuronolactone provided by the present invention, inositol is converted into a glucuronic acid solution under the action of an enzyme, and then a crude product of glucuronolactone is prepared by steps of filtration, ion exchange, decolorization, thermal concentration, and lactonization crystallization. The present invention uses inositol as a raw material, and the conversion of inositol into glucuronic acid can be completed under normal pressure and reaction conditions of 30-40 °C. Moreover, the reaction process is an enzyme-catalyzed conversion, and there is no highly polluting process such as an oxidation reaction. This solves the problems in the prior art of the nitric acid oxidation method using starch as a raw material, such as low extraction rate of the crude product, severe operating pressure, strict equipment requirements, high energy consumption, and environmental pollution. At the same time, the present invention uses inositol as a raw material, which is a new process different from the process using starch as a raw material, and has the advantages of low production cost, short cycle, and industrialization. In summary, the process for preparing glucuronolactone using inositol as a raw material and combining the steps of filtration, ion exchange, decolorization, thermal concentration, and lactonization crystallization in sequence has the advantages of simple operating conditions, environmental protection and no pollution, and high extraction rate of the crude product, has good economy, environmental protection, and operability, and has the basis for large-scale industrial production. Specific Embodiments

[0014] In order to make the technical problems, technical solutions and beneficial effects to be solved by 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 used to explain the present invention and are not used to limit the present invention.

[0015] In the prior art, in the production process of glucuronolactone, the nitric acid oxidation method mainly using starch as a raw material is adopted. In this method, starch and nitric acid are first oxidized in a reaction kettle to obtain glucuronic acid, and then glucuronic acid and glacial acetic acid are mixed for lactonization reaction to obtain glucuronolactone. In the above preparation process, on the one hand, the reaction between starch and nitric acid is an exothermic oxidation reaction, which will not only generate polluting NO2 gas, causing environmental pollution, but also the generated heat will cause the temperature in the reaction kettle to be too high, resulting in more serious carbonization of the reaction product, thus causing a loss in yield. On the other hand, in the process of starch oxidation, it needs to be carried out in a reaction kettle, and the reaction conditions generally need to reach an internal pressure of 245.25 kPa (2.5 kgf / cm 2), at a temperature of 140 - 142 °C, the conditions of high pressure and high temperature result in strict requirements for equipment during the reaction process. Additionally, the generation of the polluting gas NO2 requires an additional tail gas treatment device, overall increasing the complexity of the equipment and the floor area. On the other hand, after obtaining glucuronic acid, in the existing technology, the lactonization crystallization step is generally carried out directly on it. However, the extraction rate of glucuronolactone in this way is low, resulting in low economy in the production process.

[0016] To solve the above problems, the present invention provides a method for preparing glucuronolactone, comprising the following steps:

[0017] Adding inositol oxidase to an inositol feed solution for conversion to obtain a conversion solution;

[0018] The conversion solution is filtered to obtain a filtrate,

[0019] The filtrate is subjected to ion exchange to obtain a desalted solution,

[0020] The desalted solution is decolorized to obtain a decolorized solution,

[0021] The decolorized solution is thermally concentrated to obtain a concentrated solution,

[0022] The concentrated solution is subjected to lactonization crystallization to obtain a crude glucuronolactone.

[0023] In the present invention, inositol oxidase is added to an inositol feed solution for conversion to obtain a conversion solution. In the present invention, the conversion is carried out under atmospheric pressure and at a reaction temperature of 30 - 40 °C. The present invention has no special requirements for the source of the inositol feed solution, and it can be obtained by using those well-known to those skilled in the art or prepared by oneself. When the inositol feed solution is provided by a self-preparation method, the method for preparing glucuronolactone specifically comprises the following steps: prefabricating an inositol feed solution, and adding inositol oxidase to the inositol feed solution for conversion. In the present invention, the concentration of the inositol feed solution is preferably 10 - 100 g / L, more preferably 50 g / L; the reaction temperature of the conversion is preferably 30 - 40 °C, and the reaction pH value is preferably 8.0 - 9.0. In the examples of the present invention, the conversion reaction of inositol and inositol oxidase can specifically refer to Chinese Patent CN109423469A. The solid content of the obtained conversion solution is preferably 3 - 7%, further preferably 3%, 4%, 5%, 6% or 7%. It should be understood that the conversion solution with the above solid content has an appropriate consistency, which has obvious benefits for the subsequent filtration, desalting, and decolorization steps and operations. Generally speaking, the solid content of the conversion solution obtained by reacting the prefabricated inositol feed solution and inositol oxidase can meet the requirements, and no additional dilution or concentration operation is required.

[0024] The present invention can complete the conversion of inositol to glucuronic acid through inositol oxidase without high pressure and high heat, and the reaction process is a catalytic conversion without high-pollution processes such as oxidation reactions, solving the problems of severe operating pressure, strict equipment requirements, high energy consumption, and environmental pollution in the existing nitric acid oxidation method using starch as a raw material.

[0025] After obtaining the conversion solution, the present invention filters the conversion solution to obtain a filtrate. In the present invention, the filtration preferably includes plate-and-frame filtration or ceramic membrane filtration. The pore size of the filter membrane for plate-and-frame filtration can be selected to be 10-100 nm. In the examples of the present invention, any value within the range of 10-100 nm can be selected as the pore size of the filter membrane; specifically, the pore size of the filter membrane for plate-and-frame filtration can be selected to be 10 nm, 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, or 100 nm. The present invention has no special requirements for the equipment of the plate-and-frame filtration, nor for other parameters of the plate-and-frame filtration such as the number of filter mesh layers, filtration pressure, water flow rate, etc., as long as the filtration under a filter membrane pore size of 10-100 nm can be achieved. However, through experimental verification, when the filtration pressure is 0.6 MPa and the flow rate is 150 L / h·㎡, a better effect can be achieved (the plate-and-frame clear liquid is clear and there are no visible impurities). The separation pore size of the ceramic membrane can be selected to be 20-100 nm. In the examples of the present invention, any value within the range of 20-100 nm can be selected as the separation pore size of the ceramic membrane; specifically, the separation pore size of the ceramic membrane can be selected to be 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm. Preferably, when the pore size of the ceramic membrane is 50 nm, a better production filtration effect can be achieved, and the ceramic membrane clear liquid is clear and there are no visible impurities. The present invention has no special requirements for the type of the ceramic membrane. Exemplarily, the ceramic membrane can be a tubular ceramic membrane or a flat ceramic membrane. The present invention has no special requirements for the main material of the ceramic membrane. Exemplarily, inorganic ceramic materials such as alumina, zirconia, titanium oxide, and silicon oxide can be used. It should be understood that the function of the plate-and-frame filtration or ceramic membrane filtration in the present invention is to filter out insoluble impurities in the solution to achieve the purpose of preliminary purification.

[0026] After obtaining the filtrate, the present invention performs ion exchange on the filtrate to obtain a desalted solution. In the present invention, the ion exchange preferably uses ion exchange resin; the conductivity of the desalted solution obtained by ion-exchanging the filtrate in the present invention is < 7000 us / cm. In the present invention, the ion exchange resin preferably includes a cation exchange resin, and more preferably includes a strongly acidic cation exchange resin. It should be understood that different from obtaining glucuronic acid solution by starch oxidation method or directly preparing glucuronic acid solution, a certain amount of salt will be introduced during the preparation of glucuronic acid solution by inositol conversion, and the presence of salt may affect the subsequent crystallization process. Therefore, the present invention performs desalination by ion exchange and controls the desalination conductivity. The lower the desalination conductivity, the easier it is to obtain crystals. Through experimental verification, by controlling the desalination conductivity < 7000 us / cm, crystals with uniform particle size and larger particle size can be obtained. In addition, the resin can be reused multiple times, is easy to operate, has high safety, and is easy to realize industrial production.

[0027] Further, in combination with the above embodiments, the embodiments of the present invention further limit that in the step of obtaining a decolorized solution by decolorizing the desalted solution, the decolorizing method includes decolorization with activated carbon or decolorization with an adsorption resin, and a decolorized solution is obtained after decolorization. When decolorization with activated carbon is used, the addition amount of the activated carbon can be selected as 1-5% of the mass of the desalted solution. Specifically, the addition amount of the activated carbon can be selected as 1%, 2%, 3%, 4%, or 5%. The present invention has no special requirements for the decolorization time, and it can be carried out according to the common standards in production. For example, it can be determined by observing the color of the solution or according to the conventional time obtained from the production experience in the art. The present invention has no special requirements for the micropore diameter and surface area of the activated carbon. By way of example, the activated carbon can be medicinal activated carbon. When decolorization with an adsorption resin is used, by way of example, the adsorption resin can be a macroporous adsorption resin; specifically, the macroporous adsorption resin can be LS-108 or LS-109D, which further decolorizes the glucuronic acid solution obtained by the reaction of inositol and inositol oxidase, further improves the purity of the glucuronic acid solution, facilitates the subsequent esterification reaction, and improves the extraction rate of glucuronolactone.

[0028] Further, in combination with the above embodiments, the embodiments of the present invention further limit that in the step of obtaining a concentrated solution by thermally concentrating the decolorized solution, the steps of thermal concentration include: using a concentrator to concentrate the decolorized solution to a concentrated solution with a solid content of 50-70%. Specifically, the solid content of the decolorized solution can be 50%, 55%, 60%, 65%, or 70%. Further, through the tests by the inventor, at this solid content, the glucuronic acid concentrated solution is easy to obtain, the concentration energy consumption is low, no additional acid needs to be added during the crystallization process, the time consumption is short, which further shortens the equilibrium time of the lactonization reaction and lays a foundation for the lactonization reaction. Moreover, the dissolution loss of glucuronolactone in water is reduced or avoided during the concentration process, thereby improving the crystallization yield of glucuronolactone.

[0029] Furthermore, the thermal concentration is carried out at 60 - 80°C under a vacuum of < -0.09 MPa, which can easily evaporate the moisture in the feed liquid to achieve the purpose of concentration. Moreover, the concentration equipment is common and the technology is mature in industrial production, making it easy to realize industrial production.

[0030] Furthermore, in combination with the above embodiments, the embodiments of the present invention further define that in the step of obtaining the crude gluconolactone by lactonization crystallization of the concentrated liquid, the steps of the lactonization crystallization include: mixing the concentrated liquid and glacial acetic acid for an esterification reaction, performing vacuum distillation after the reaction, and then obtaining the crude gluconolactone by cooling crystallization.

[0031] Furthermore, in combination with the above embodiments, the embodiments of the present invention further define that the addition amount of the glacial acetic acid is 0.8 - 1.8 times the volume of the concentrated liquid.

[0032] Furthermore, in combination with the above embodiments, the embodiments of the present invention further define that the temperature of the lactonization reaction is 50 - 70°C and the reaction time is 5 - 10 h.

[0033] Furthermore, in combination with the above embodiments, the embodiments of the present invention further define that the temperature of the vacuum distillation is 50 - 70°C, the vacuum is -0.09 MPa, and the volume of the distillate is 30 - 50% of the addition amount of the glacial acetic acid.

[0034] Furthermore, in combination with the above embodiments, the embodiments of the present invention further define that the cooling crystallization is carried out by gradient cooling crystallization at a rate of 5 - 10°C / h, and the crystallization termination temperature is 5 - 15°C.

[0035] By adopting the above technical solutions, during the whole lactonization crystallization process, through dynamic gradient cooling crystallization, the particle size of the gluconolactone crystals obtained is uniform, easy to filter, and the purity of the gluconolactone product is also improved. At the same time, the crystallization termination temperature of the crystallization process is 5 - 15°C, which can improve the crystallization yield while reducing energy consumption. At the same time, the reaction system is a solid-liquid mixed system after the reaction, which is easy to separate and filter the gluconolactone. The crystallization process has simple operation. The content of gluconolactone in the crude gluconolactone obtained by adopting the above technical solutions is ≥95%, and the crystallization rate is ≥80%.

[0036] Furthermore, in combination with the above embodiments, after obtaining the conversion liquid and before filtration, the embodiments of the present invention further include adding chitosan to the conversion liquid, and then performing plate-and-frame filtration or directly filtering the conversion liquid through a ceramic membrane. It should be understood that the chitosan in the present invention is used as a flocculant, specifically a cationic flocculant, and there is no special requirement for its variety, and a commercially available chitosan flocculant can be used.

[0037] Further, in combination with the above embodiments, after the conversion liquid is filtered and before ion exchange, the embodiments of the present invention further include: performing ultrafiltration membrane filtration on the filtrate to obtain an ultra-clear filtrate; the pore size of the ultrafiltration membrane is selected to be 5000-20000Da.

[0038] Further, in combination with the above embodiments, after the conversion liquid is decolorized and before thermal concentration, the embodiments of the present invention further include: performing nanofiltration membrane concentration on the decolorized liquid to obtain a nanofiltration decolorized liquid; the pore size of the nanofiltration membrane is 150-300Da, and the solid content of the nanofiltration decolorized liquid is 10-15%.

[0039] Adopting the above technical solution, before and after the esterification reaction, the embodiments of the present invention respectively adopt two-stage dehydration operations of thermal concentration and vacuum distillation, reducing or avoiding the dissolution loss of glucuronolactone in water, thereby improving the crystallization yield of glucuronolactone.

[0040] Through the separation and purification processes such as filtration, ion exchange, and decolorization adopted after inositol conversion, the present invention solves the problem of low crude product extraction rate in the prior art for the preparation of glucuronolactone using starch as a raw material. In summary, the present invention uses inositol as a raw material, and combines the steps of filtration, ion exchange, decolorization, thermal concentration, and lactonization crystallization in sequence to prepare glucuronolactone. The process has the advantages of simple operating conditions, environmental protection and no pollution, and high crude product extraction rate, and has good economy, environmental protection and operability, and has the basis for large-scale industrial production.

[0041] Further, the embodiments of the present invention further include further refining the above-mentioned crude glucuronolactone, and the refining method can adopt the existing / commonly used methods in the art, and the present invention does not make special limitations on it.

[0042] To better illustrate the technical solution of the present invention, the present invention also provides the following specific embodiments. It should be understood that the raw materials used in the following embodiments are all commercially available raw materials unless otherwise specified.

[0043] Example 1

[0044] This example provides a method for preparing glucuronolactone, and the steps are as follows:

[0045] S1. Prepare 60L of 50g / L inositol feed liquid, add inositol oxidase to make the bacterial concentration in the system reach 30OD, perform conversion at 37°C and pH = 8 to obtain 64.5L of conversion liquid. After adding 3.0L of chitosan solution for flocculation, collect 71.2L of filtrate through plate-frame filtration with a pore size of 50nm under a filtration pressure of 0.6MPa and a flow rate of 150L / h·㎡, and collect 78L of ultrafiltration membrane clear liquid through ultrafiltration membrane filtration of the filtrate;

[0046] S2. At a flow rate of 22 L / h, the above filtrate was desalted by 15 L of cation exchange resin to obtain 82.2 L of desalted liquid, and the conductivity of the desalted liquid was 6200 us / cm;

[0047] S3. 3% medicinal activated carbon was added to the above desalted liquid for decolorization, and the decolorized liquid was collected after decolorization;

[0048] S4. The above decolorized liquid was concentrated at 70 °C and -0.09 MPa to obtain 4.4 L of concentrated liquid with a solid content of 62%;

[0049] S5. 4.4 L of glacial acetic acid was added to the above concentrated liquid for lactonization reaction at 60 °C. After reacting for 6 h, 2.1 L of acid water was distilled off at 60 °C and a vacuum degree of -0.09 MPa, and then dynamic gradient cooling crystallization was carried out at a rate of 8 °C / h. The crystallization termination temperature was 9 °C. The crystallization mixture was filtered by suction to obtain 2.4 kg of crude glucuronolactone (white crystalline particles). The purity was detected by a liquid chromatograph to be 98.2%, and the crystallization yield was 81.49%. This crude product can be used for subsequent purification.

[0050] Example 2

[0051] This example provides a method for preparing glucuronolactone, which includes the following steps:

[0052] S1. Prepare 60 L of inositol feed liquid at 50 g / L, add inositol oxidase to make the cell concentration in the system reach 30 OD, and carry out conversion at 37 °C and pH = 8 to obtain 63 L of conversion liquid. The conversion liquid was filtered through a ceramic membrane with a pore size of 50 nm to collect 72 L of filtrate, and the filtrate was filtered through an ultrafiltration membrane to collect 78 L of ultrafiltration membrane permeate;

[0053] S2. At a flow rate of 22 L / h, the above filtrate was desalted by 15 L of cation exchange resin to obtain 81 L of desalted liquid, and the conductivity of the desalted liquid was 5800 us / cm;

[0054] S3. 5% medicinal activated carbon was added to the desalted liquid for decolorization, and the decolorized liquid was collected after decolorization;

[0055] S4. The decolorized liquid was concentrated at 60 °C and -0.09 MPa to obtain 4.3 L of concentrated liquid with a solid content of 50%;

[0056] In S5, 4.2 L of glacial acetic acid was added to the concentrated solution for lactonization reaction. The lactonization reaction temperature was 50 °C. After reacting for 10 h, 2 L of acid water was distilled off at the same temperature as the lactonization reaction and a vacuum degree of -0.09 MPa. Then, dynamic gradient cooling crystallization was carried out at a rate of 5 °C / h, and the crystallization termination temperature was 5 °C. The crystallization mixture was filtered by suction to obtain 2.38 kg of crude glucuronolactone (white crystalline particles). The purity was detected to be 98.2% by a liquid chromatograph, and the crystallization yield was 82.08%. This crude product can be used for subsequent purification.

[0057] Example 3

[0058] This example provides a preparation method of glucuronolactone, which includes the following steps:

[0059] In S1, 60 L of 50 g / L inositol feed liquid was prepared, inositol oxidase was added to make the bacterial concentration in the system reach 30 OD, and conversion was carried out at 37 °C and pH = 8 to obtain 63 L of conversion liquid. The conversion liquid was filtered through a ceramic membrane with a pore size of 50 nm to collect 72 L of filtrate, and the filtrate was filtered through an ultrafiltration membrane to collect 78 L of ultrafiltration membrane supernatant;

[0060] In S2, at a flow rate of 22 L / h, the above filtrate was desalted by 15 L of cation exchange resin to obtain 85 L of desalted liquid, and the conductivity of the desalted liquid was 6500 us / cm;

[0061] The desalted liquid passed through a 6 L macroporous adsorption resin column for decolorization, and the decolorized liquid was collected after decolorization to obtain 85 L of decolorized liquid;

[0062] In S4, the decolorized liquid was concentrated at 60 °C and -0.09 MPa to obtain 4.1 L of concentrated solution with a solid content of 70%;

[0063] In S5, 5 L of glacial acetic acid was added to the concentrated solution for lactonization reaction. The lactonization reaction temperature was 70 °C. After reacting for 8 h, 2 L of acid water was distilled off at the same temperature as the lactonization reaction and a vacuum degree of -0.09 MPa. Then, dynamic gradient cooling crystallization was carried out at a rate of 5 °C / h, and the crystallization termination temperature was 10 °C. The crystallization mixture was washed with 2 L of absolute ethanol and dried to obtain 2.39 kg of crude glucuronolactone (white crystalline particles). The purity was detected to be 98.2% by a liquid chromatograph, and the crystallization yield was 82.78%. This crude product can be used for subsequent purification.

[0064] Example 4

[0065] This example provides a preparation method of glucuronolactone, which includes the following steps:

[0066] S1. Prepare 60 L of 50 g / L inositol feed solution, add inositol oxidase to make the cell concentration in the system reach 30 OD, and perform transformation at 37 °C and pH = 8 to obtain 63 L of transformation solution. The transformation solution is filtered through a ceramic membrane with a pore size of 50 nm to collect 72 L of filtrate. The filtrate is filtered through an ultrafiltration membrane to collect 78 L of ultrafiltration membrane permeate;

[0067] S2. At a flow rate of 22 L / h, the above filtrate is desalted by 15 L of cation exchange resin to obtain 92 L of desalted solution, and the conductivity of the desalted solution is 5500 us / cm;

[0068] S3. The desalted solution is decolorized by a 6 L macroporous adsorption resin column, and 97 L of decolorized solution is collected after decolorization;

[0069] S4. The decolorized solution is concentrated at 80 °C and -0.09 MPa to obtain 4.1 L of concentrated solution with a solid content of 65%;

[0070] S5. 6 L of glacial acetic acid is added to the concentrated solution for lactonization reaction. The lactonization reaction temperature is 70 °C. After reacting for 5 h, 2 L of acid water is distilled off at the same temperature as the lactonization reaction and a vacuum degree of -0.09 MPa. Then, dynamic gradient cooling crystallization is carried out at a rate of 7 °C / h, and the crystallization termination temperature is 15 °C. The crystallization mixture is washed with 2 L of absolute ethanol and dried to obtain 2.4 kg of crude glucuronolactone (white crystalline particles). The purity is detected by a liquid chromatograph to be 97.7%, and the crystallization yield is 82.68%. This crude product can be used for subsequent refining.

[0071] Example 5

[0072] This example provides a method for preparing glucuronolactone, including the following steps:

[0073] S1. Prepare 60 L of 50 g / L inositol feed solution, add inositol oxidase to make the cell concentration in the system reach 30 OD, and perform transformation at 37 °C and pH = 8 to obtain 63 L of transformation solution. The transformation solution is filtered through a ceramic membrane with a pore size of 50 nm to collect 72 L of filtrate; The filtrate is filtered through an ultrafiltration membrane to collect 81 L of ultrafiltration membrane permeate;

[0074] S2. At a flow rate of 22 L / h, the above ultrafiltration membrane filtrate is desalted by 15 L of cation exchange resin to obtain 92 L of desalted solution, and the conductivity of the desalted solution is 6300 us / cm;

[0075] S3. The desalted solution is decolorized by a 6 L macroporous adsorption resin column, and 97 L of decolorized solution is collected after decolorization;

[0076] S4. The decolorized solution is concentrated by nanofiltration membrane at 80 °C and -0.09 MPa, 23 L of nanofiltration decolorized solution is collected, and the nanofiltration decolorized solution is concentrated to obtain 4.2 L of concentrated solution with a solid content of 65%;

[0077] S5. 3.5 L of glacial acetic acid was added to the concentrated solution for lactonization reaction. The temperature of the lactonization reaction was 50 °C. After reacting for 10 h, 2.1 L of acid water was distilled off at the same temperature as the lactonization reaction and a vacuum degree of 0.09 MPa. Then, dynamic gradient cooling crystallization was carried out at a rate of 10 °C / h, and the crystallization termination temperature was 9 °C. The crystallization mixture was washed with 2 L of absolute ethanol and dried to obtain 2.98 kg of crude glucuronolactone (white crystalline particles). The purity was detected by a liquid chromatograph to be 97.5%, and the crystallization yield was 82.28%. This crude product can be used for subsequent purification.

[0078] Comparative Example 1

[0079] Compared with Example 1, after preparing the prefabricated inositol feed liquid, a gluconic acid solution with the same volume and concentration was prepared by the starch oxidation method, and other reaction conditions remained unchanged.

[0080] After testing, the purity of the finished product obtained under this reaction system was 78.6%, and the purification yield was 65.8%.

[0081] It is speculated that the reason may be that the composition of the gluconic acid solution prepared by the starch oxidation method is different from that of the gluconic acid solution prepared from inositol in the present invention. Under the same subsequent process, the process of the present invention is not compatible with the process of the starch oxidation method and cannot achieve the same technical effect.

[0082] Comparative Example 2

[0083] Compared with Example 2, the ultrafiltration membrane filtration step was cancelled, and the ceramic membrane filtrate was directly desalted by ion exchange resin, and other reaction conditions remained unchanged.

[0084] Under this condition, the purity of the finished product obtained in the reaction system was 88.4%, and the crystallization yield was 61%. The color of the finished product was visibly different from that of Example 2.

[0085] It is speculated that the reason may be that after cancelling the ultrafiltration process, the impurities present in the solution cannot be effectively removed in the subsequent process and still remain in the crude glucuronolactone extract after crystallization, reducing the purity of the product and causing an obvious color difference.

[0086] Comparative Example 3

[0087] Compared with Example 3, the solid content obtained in the concentration process was adjusted to 30%, and other reaction conditions remained unchanged.

[0088] Under this condition, the purity of the finished product obtained in the reaction system was 90.1%, and the crystallization yield was 21%.

[0089] It is speculated that the reason may be that the solid content of the concentrated solution is low, resulting in a high solubility of glucuronolactone in the solution, a longer lactonization reaction time, more by-products, and inefficient crystallization and precipitation.

[0090] Comparative Example 4

[0091] Compared with Example 4, the vacuum distillation step in the lactonization crystallization step was cancelled, and other reaction conditions remained unchanged.

[0092] The purity of the finished product obtained under this condition in the reaction system was 90.3%, and the crystallization yield was 16%.

[0093] It is speculated that the reason may be that the solid content of the concentrated solution is low, resulting in a high solubility of glucono delta-lactone in the solution, and thus excessive glucono delta-lactone is dissolved and lost in water.

[0094] Comparative Example 5

[0095] Compared with Example 5, by controlling the amount of resin selected, the conductivity of the desalted liquid in step S2 was 8000 us / cm, and other reaction conditions remained unchanged.

[0096] The purity of the finished product obtained under this condition in the reaction system was 90.2%, and the crystallization yield was 56.7%.

[0097] Comparative Example 6

[0098] Compared with Example 5, the dynamic gradient cooling process in S5 was cancelled and changed to natural cooling, and other reaction conditions remained unchanged.

[0099] The purity of the finished product obtained under this condition in the reaction system was 89.6%, and the crystallization yield was 40.5%.

[0100] *Test Example

[0101] Furthermore, the liquid chromatography test conditions in Examples 1 to 5 and Comparative Example 1-4-5 of the present invention are as follows:

[0102] Mobile phase: 10 mmol / L formic acid aqueous solution;

[0103] Chromatographic column: calcium column (300*7.7 or similar column);

[0104] Flow rate: 0.5 Ml / min;

[0105] Detector: differential detector;

[0106] Column temperature: 55 °C;

[0107] Detector temperature: 45 °C;

[0108] Solvent: 10 mmol / L formic acid aqueous solution;

[0109] Standard concentration: 1.0 mg / mL (D-gluconolactone

CAS No.

[0110] Test sample concentration: 1.0 mg / mL;

[0111] Chromatographic conditions: Run with 100% 10 mmol / L formic acid aqueous solution for 30 min.

[0112] The above are only the preferred embodiments of the present invention and are 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 perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing glucuronic lactone, characterized in that, It includes the following steps: Add inositol oxidase to the inositol feed liquid for conversion to obtain a conversion liquid. The concentration of the inositol feed liquid is 10 - 100 g / L, the reaction temperature for the conversion is 30 - 40 °C, and the pH value is 8.0 - 9.0; The conversion liquid is filtered through a plate and frame filter or a ceramic membrane filter to obtain a filtrate. The pore size of the filter membrane for the plate and frame filter is 10 - 100 nm; the separation pore size of the ceramic membrane is 20 - 100 nm; The filtrate is subjected to ion exchange to obtain a desalted liquid, and the conductivity of the desalted liquid < 7000 us / cm; The desalted liquid is decolorized with activated carbon or adsorption resin to obtain a decolorized liquid; The decolorized liquid is thermally concentrated to a solid content of 50 - 70% to obtain a concentrated liquid; Mix the concentrated liquid and glacial acetic acid for lactonization reaction. After the reaction, perform vacuum distillation, and then cool and crystallize to obtain crude glucuronolactone; wherein, the addition amount of the glacial acetic acid is 0.8 - 1.8 times the volume of the concentrated liquid, the temperature of the lactonization reaction is 50 - 70 °C, and the reaction time is 5 - 10 h.

2. The preparation method according to claim 1, characterized in that, The ion exchange uses ion exchange resin.

3. The preparation method according to claim 1, characterized in that, When using the activated carbon for decolorization, the addition amount of the activated carbon is 1 - 5% of the mass of the desalted liquid.

4. The preparation method according to claim 1, characterized in that, The temperature for the vacuum distillation is 50 - 70 °C, the vacuum degree is -0.09 MPa, and the volume of the distillate is 30 - 50% of the addition amount of the glacial acetic acid; The cooling crystallization is carried out by gradient cooling crystallization at a rate of 5 - 10 °C / h, and the crystallization termination temperature is 5 - 15 °C.

5. The preparation method according to claim 1, characterized in that, After the conversion liquid is filtered to obtain a filtrate and before the filtrate is subjected to ion exchange to obtain a desalted liquid, it further includes: filtering the filtrate through an ultrafiltration membrane to obtain an ultra-clear filtrate; the pore size of the ultrafiltration membrane is 5000 - 20000 Da.

6. The preparation method according to claim 1, characterized in that, After the desalted liquid is decolorized to obtain a decolorized liquid and before the decolorized liquid is thermally concentrated to obtain a concentrated liquid, it further includes: concentrating the decolorized liquid through a nanofiltration membrane to obtain a nanofiltration decolorized liquid; the pore size of the nanofiltration membrane is 150 - 300 Da, and the solid content of the nanofiltration decolorized liquid is 10 - 15%.