CN116179625A - Preparation method of glucurolactone - Google Patents
Preparation method of glucurolactone Download PDFInfo
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- CN116179625A CN116179625A CN202310263076.2A CN202310263076A CN116179625A CN 116179625 A CN116179625 A CN 116179625A CN 202310263076 A CN202310263076 A CN 202310263076A CN 116179625 A CN116179625 A CN 116179625A
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Abstract
The invention discloses a preparation method of glucurolactone, and relates to the technical field of esterification reaction. The method comprises the following steps: and adding inositol oxidase into the inositol feed liquid to perform conversion to obtain conversion liquid, and sequentially performing the steps of filtering, ion exchange, decoloring, thermal concentration and lactonization crystallization on the conversion liquid to obtain a crude product of the glucurolactone. The preparation method of the invention takes inositol as a raw material, converts the inositol into glucuronic acid solution under the action of enzyme, and adopts the steps of filtration, ion exchange, decoloration, thermal concentration and lactonization crystallization to prepare the crude product of the glucurolactone. The invention solves the problems of low crude product extraction rate, strict operating pressure, strict equipment requirements and environmental pollution existing in the nitric acid oxidation method which takes starch as raw material, and simultaneously takes inositol as raw material, which is a new process different from the process which takes starch as raw material, and has the advantages of low production cost, short period and industrialization.
Description
Technical Field
The invention relates to the technical field of esterification reaction, in particular to a preparation method of glucurolactone.
Background
Glucuronolactone chinese full name glucuronic acidLactone, commonly known as Gantaile, has a molecular formula of C 6 H 8 O 6 The chemical composition of the compound is D (+) -furan glucuronic acid gamma-lactone, and the English name is [ D (+) -Glucofuranurono-6,3-lactone]. The glucurolactone is used as a liver antidote and an immune function regulator, and is a conventional liver-protecting good medicine; the glucurolactone and the subsequent products thereof are also main additives of functional beverages, foods, weight-reducing drugs, cosmetics and the like, and have the effects of supplementing physical energy, improving hypoxia, nourishing skin and delaying aging.
In the prior art, the main method for producing glucurolactone is a nitric acid oxidation method which takes starch as a raw material, and comprises the following steps: adding starch into nitric acid with the content of about 80% (V/V) for oxidation to obtain starch oxidation solution, heating and pressurizing the obtained starch oxidation solution under an acidic condition for hydrolysis to obtain hydrolysis solution with glucuronic acid as a main component, concentrating the hydrolysis solution under reduced pressure, adding a complex acid reagent or glacial acetic acid consisting of phosphoric acid and sulfuric acid for esterification reaction, and adding ethanol for recrystallization after the esterification reaction is finished to obtain a glucurolactone crude product. In the above technical scheme, the process of nitric acid oxidizing starch to obtain hydrolysis liquid of glucuronic acid is carried out in a high-pressure reaction kettle, wherein the pressure during the reaction in the kettle is generally controlled to 245.25kPa (2.5 kgf/cm) 2 ) Left and right; the method has the problems of low crude product extraction rate, strict equipment requirement and severe operating pressure, and simultaneously, the nitric acid oxidation process also causes great pollution to the environment.
In addition, the related method for preparing glucurolactone by using inositol as a raw material is not disclosed in the prior art for a while, and the invention is a novel process which is different from the process by using starch as a raw material.
Disclosure of Invention
In view of the above, the invention aims to provide a preparation method of glucurolactone, which is used for solving the problems of harsh and complex preparation process, low crude product extraction rate and the like of the glucurolactone in the prior art.
In order to achieve the above object, the present invention provides the following technical solutions: the invention provides a preparation method of glucurolactone, which comprises the following steps:
adding inositol oxidase into the inositol feed liquid to perform conversion to obtain conversion liquid;
the conversion solution is filtered to obtain filtrate,
the filtrate is subjected to ion exchange to obtain desalted liquid,
the desalted liquid is decolorized to obtain decolorized liquid,
the decolorized solution is thermally concentrated to obtain concentrated solution,
and (3) carrying out lactonization crystallization on the concentrated solution to obtain a crude product of the glucurolactone.
The preparation method of the glucurolactone provided by the invention converts inositol into glucuronic acid solution under the action of enzyme, and then adopts the steps of filtering, ion exchange, decoloring, thermal concentration and lactonization crystallization to prepare the crude product of the glucurolactone. The invention takes inositol as raw material, can complete the conversion of inositol to glucuronic acid under the reaction conditions of normal pressure and 30-40 ℃, and the reaction process is enzyme catalytic conversion, so that the high pollution process such as oxidation reaction is not existed, and the problems of low crude product extraction rate, strict operation pressure, strict equipment requirement, high energy consumption, environmental pollution and the like existing in the nitric acid oxidation method taking starch as raw material in the prior art are solved; meanwhile, the invention takes inositol as a raw material, is a novel process different from the process taking starch as a raw material, and has the advantages of low production cost, short period and industrialization. In conclusion, the invention uses inositol as raw material, combines the steps of filtering, ion exchange, decoloring, thermal concentration and lactonization crystallization sequentially, and the process for preparing the glucurolactone has the advantages of simple operation condition, environmental protection, no pollution, high extraction rate of crude products and the like, has good economy, environmental protection and operability, and has the basis of large-scale industrial production.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved more clear, the invention is further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
In the prior art, in the production process of glucurolactone, a nitric acid oxidation method which takes starch as a raw material is mainly adopted, and the method firstly comprises the steps ofOxidizing acid in a reaction kettle to obtain glucuronic acid, and then mixing glucuronic acid and glacial acetic acid to carry out a lactonization reaction to obtain glucurolactone. In the above preparation process, on the one hand, the reaction of starch and nitric acid is an exothermic oxidation reaction, which not only produces polluting NO 2 The gas causes environmental pollution, and the generated heat also causes the temperature in the reaction kettle to be too high, so that the reaction product is carbonized more seriously, thereby causing yield loss; on the other hand, in the starch oxidation process, it is necessary to carry out the reaction in a reaction vessel, and the reaction conditions are generally such that the internal pressure of 245.25kPa (2.5 kgf/cm) 2 ) The temperature is 140-142 ℃, the high pressure and high temperature conditions lead to strict requirements on equipment in the reaction process, and the pollution gas NO 2 The generation of the exhaust gas treatment device is additionally needed, so that the complexity and the occupied area of the equipment are increased as a whole; on the other hand, although the prior art generally carries out the lactonization crystallization step directly after the glucuronic acid is obtained, the extraction rate of the glucuronolactone in this way is low, which results in low economical production process.
In order to solve the problems, the invention provides a preparation method of glucurolactone, which comprises the following steps:
adding inositol oxidase into the inositol feed liquid to perform conversion to obtain conversion liquid;
the conversion solution is filtered to obtain filtrate,
the filtrate is subjected to ion exchange to obtain desalted liquid,
the desalted liquid is decolorized to obtain decolorized liquid,
the decolorized solution is thermally concentrated to obtain concentrated solution,
and (3) carrying out lactonization crystallization on the concentrated solution to obtain a crude product of the glucurolactone.
In the invention, inositol oxidase is added into inositol feed liquid for conversion to obtain conversion liquid. In the present invention, the conversion is carried out under reaction conditions of normal pressure and 30 to 40 ℃. The source of the inositol feed solution is not particularly required in the invention, and the inositol feed solution can be prepared by the method well known to the person skilled in the art or by self. When the inositol feed liquid is provided by adopting a self-preparation method, the preparation method of the glucurolactone specifically comprises the following steps: preparing inositol feed liquid, and adding inositol oxidase into the inositol feed liquid for conversion. In the present invention, the concentration of the inositol feed solution is preferably 10 to 100g/L, more preferably 50g/L; the reaction temperature of the conversion is preferably 30-40 ℃, and the reaction pH value is preferably 8.0-9.0. In the examples of the present invention, the conversion reaction of inositol with inositol oxidase can be specifically carried out with reference to chinese patent CN109423469 a. The solid content of the obtained conversion solution is preferably 3 to 7%, more preferably 3%, 4%, 5%, 6% or 7%. It will be appreciated that the above-described solids conversion solution is suitably thin and of significant benefit to the performance and operation of the subsequent filtration, desalination and decolorization steps. Generally, the solid content of the conversion liquid obtained by reacting the pre-prepared inositol feed liquid with inositol oxidase can meet the requirement, and no additional dilution or concentration operation is required.
The invention can complete the conversion of inositol to glucuronic acid through inositol oxidase without high pressure and high heat, and the reaction process is catalytic conversion, so that the high pollution process such as oxidation reaction is not existed, and the problems of strict operation pressure, strict equipment requirement, high energy consumption, environmental pollution and the like existing in the nitric acid oxidation method which takes starch as raw material in the prior art are solved.
After the conversion liquid is obtained, the conversion liquid is filtered to obtain filtrate. In the present invention, the filtration preferably includes a plate frame filtration or a ceramic membrane filtration. The pore size of the filter membrane for plate and frame filtration can be selected to be 10-100nm. In the embodiment of the invention, any value with the aperture within the range of 10-100nm can be selected as the aperture of the filter membrane; specifically, the pore size of the plate-frame filtration membrane can be selected to be 10nm, 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm or 100nm. The invention has no special requirements on the plate and frame filtering equipment, and has no special requirements on other parameters of the plate and frame filtering, such as the number of layers of a filter screen, the filtering pressure, the water flow and the like, so long as the filtering under the aperture of a filter membrane with the diameter of 10-100nm can be realized. However, it is verified by test that when the filtration pressure is 0.6MPa and the flow is 150L/h square meter, a better effect (clear plate and frame clear liquid without visible impurities) can be achieved. The separation pore diameter of the ceramic membrane can be selected to be 20-100nm. In the embodiment of the invention, any value with the aperture within the range of 20-100nm can be selected as the separation aperture of the ceramic membrane; specifically, the separation pore diameter of the ceramic membrane may be selected from 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm. Preferably, when the pore diameter of the ceramic membrane is 50nm, the better effect of production filtration can be achieved, clear liquid of the ceramic membrane is clear, no visible impurities are required, the invention has no special requirements on the type of the ceramic membrane, and the ceramic membrane can be a tubular ceramic membrane or a flat ceramic membrane. The invention has no special requirement on the main material of the ceramic membrane, and can be exemplified by inorganic ceramic materials such as alumina, zirconia, titania, silica and the like. It should be understood that the plate-frame filtration or ceramic membrane filtration of the present invention is used to filter out insoluble impurities in the solution for primary purification.
After the filtrate is obtained, the filtrate is subjected to ion exchange to obtain the desalted liquid. In the present invention, the ion exchange is preferably performed using an ion exchange resin; the invention obtains the desalted liquid with the conductivity less than 7000us/cm after the filtrate is subjected to ion exchange. In the present invention, the ion exchange resin preferably comprises a cation exchange resin, and further preferably comprises a strongly acidic cation exchange resin. It will be appreciated that unlike the oxidation of starch to give a glucuronic acid solution or the direct preparation of a glucuronic acid solution, a certain amount of salt is carried over during the conversion of inositol to give a glucuronic acid solution, and the presence of salt may affect the subsequent crystallization process. Therefore, the invention performs desalination by ion exchange and controls the desalination conductivity, and the lower the desalination conductivity is, the easier crystallization is obtained. Experiments prove that crystals with uniform particle size and larger particle size can be obtained by controlling the desalination conductivity to be less than 7000us/cm. In addition, the resin can be repeatedly used, is easy to operate, has high safety and is easy to realize industrial production.
Further, in combination with the above embodiment, the method further defines that in the step of decolorizing the desalted liquid to obtain a decolorized liquid, the decolorization mode includes activated carbon decolorization or adsorption resin decolorization, and the decolorized liquid is obtained after decolorization. When activated carbon is used for decolorization, the addition amount of the activated carbon may be selected to be 1 to 5% by mass of the desalted liquid. Specifically, the addition amount of the activated carbon may be selected to be 1%, 2%, 3%, 4%, 5%. The time for decoloring is not particularly limited, and the decoloring can be performed according to a standard common in production, for example, by observing the color of a solution or a conventional time obtained by production experience in the field. The invention has no special requirement on the micropore diameter and the surface area of the active carbon, and the active carbon can be medicinal active carbon. When decolorizing with an adsorbent resin, the adsorbent resin may be exemplified by macroporous adsorbent resins; specifically, LS-108 or LS-109D can be selected as macroporous adsorption resin, so that the glucuronic acid solution obtained by the reaction of inositol and inositol oxidase is further decolorized, the purity of the glucuronic acid solution is further improved, the subsequent esterification reaction is facilitated, and the extraction rate of glucurolactone is improved.
Further, in combination with the above embodiment, the method further defines that in the step of thermally concentrating the decolorized solution to obtain a concentrated solution, the step of thermally concentrating includes: concentrating the decolorized solution to a concentrated solution with a solid content of 50-70% by using a concentrator. Specifically, the solid content of the decolorized solution may be 50%, 55%, 60%, 65%, 70%. Further, through the tests of the inventor, the glucuronic acid concentrated solution is easy to obtain under the solid content, the concentrating energy consumption is low, acid is not needed to be supplemented again in the crystallization process, the time consumption is short, the equilibrium time of the lactonization reaction is further shortened, and a foundation is laid for the lactonization reaction. In addition, the concentration process reduces or avoids the dissolution loss of the glucurolactone in water, thereby improving the crystallization yield of the glucurolactone.
Furthermore, the thermal concentration is carried out under the condition that the vacuum degree is less than-0.09 MPa at the temperature of 60-80 ℃, so that the moisture in the feed liquid is easily distilled out, the purpose of concentration is achieved, and the concentration equipment is common in industrial production, the technology is mature, and the industrial production is easily realized.
Further, in combination with the above embodiment, the step of obtaining a crude product of glucurolactone by lactonizing and crystallizing the concentrated solution is further defined in the embodiment of the present invention, wherein the step of lactonizing and crystallizing includes: and mixing the concentrated solution with glacial acetic acid for esterification reaction, evaporating out in vacuum after the reaction, and cooling and crystallizing to obtain a crude product of glucurolactone.
Further, in combination with the above embodiment, the embodiment of the present invention further defines that the glacial acetic acid is added in an amount of 0.8 to 1.8 times the volume of the concentrated solution.
Further, in combination with the above examples, the present invention further defines that the temperature of the lactonization reaction is 50-70 ℃ and the reaction time is 5-10h.
Further, in combination with the above embodiment, the embodiment of the present invention further defines that the vacuum distillation temperature is 50-70 ℃, the vacuum degree is-0.09 MPa, and the volume of the distilled product is 30-50% of the glacial acetic acid addition.
Further, in combination with the above embodiment, the embodiment of the present invention further defines that the cooling crystallization is a gradient cooling crystallization performed at a rate of 5-10 ℃/h, and the crystallization termination temperature is 5-15 ℃.
By adopting the technical scheme, the particle size of the obtained glucurolactone crystals is uniform and is easy to filter in the whole lactonization crystallization process through dynamic gradient cooling crystallization, and the purity of the glucurolactone product is also improved. Meanwhile, the crystallization termination temperature of the crystallization process is 5-15 ℃, so that the crystallization yield can be improved while the energy consumption is reduced. Meanwhile, the system after the reaction is a solid-liquid mixed system, and the separation and filtration of glucurolactone are easy. The crystallization process is simple to operate, and the content of the glucurolactone in the crude glucurolactone product obtained by adopting the technical scheme is more than or equal to 95%, and the crystallization rate is more than or equal to 80%.
Further, in combination with the above embodiment, the embodiment of the present invention further includes adding chitosan into the conversion solution after the conversion solution is obtained and before the filtration, and then filtering the conversion solution through a plate frame or directly filtering the conversion solution through a ceramic membrane. It should be understood that the chitosan in the invention is used as a flocculant, in particular to a cationic flocculant, and the variety of the chitosan flocculant is not particularly required, and the chitosan flocculant is commercially available.
Further, in combination with the above embodiment, the embodiment of the present invention further includes, after the conversion solution is filtered, before ion exchange: performing ultrafiltration membrane filtration on the filtrate to obtain ultra-clear filtrate; the aperture of the ultrafiltration membrane is 5000-20000Da.
Further, in combination with the above embodiment, the embodiment of the present invention further includes, after the conversion solution is decolorized, before the thermal concentration: concentrating the decolorized solution by using a nanofiltration membrane to obtain nanofiltration decolorized solution; the aperture of the nanofiltration membrane is 150-300Da, and the solid content of the nanofiltration decolorization liquid is 10-15%.
By adopting the technical scheme, the embodiment of the invention adopts two-stage dehydration operations of thermal concentration and vacuum distillation before and after the esterification reaction, so that the dissolution loss of the glucurolactone in water is reduced or avoided, and the crystallization yield of the glucurolactone is improved.
The invention solves the problem of low extraction rate of crude products in the scheme of preparing glucurolactone by taking starch as raw material in the prior art through separation and purification processes such as filtration, ion exchange, decoloration and the like adopted after inositol conversion. In conclusion, the invention uses inositol as raw material, combines the steps of filtering, ion exchange, decoloring, thermal concentration and lactonization crystallization sequentially, and the process for preparing the glucurolactone has the advantages of simple operation condition, environmental protection, no pollution, high extraction rate of crude products and the like, has good economy, environmental protection and operability, and has the basis of large-scale industrial production.
Further, the embodiment of the invention further comprises further refining the crude product of the glucurolactone, and the refining method can adopt the existing/commonly used method in the field, and the invention is not limited in particular.
In order to better explain the technical scheme of the invention, the invention also provides the following specific embodiments. It should be understood that the starting materials used in the examples below are commercially available unless otherwise specified.
Example 1
The embodiment provides a preparation method of glucurolactone, which comprises the following steps:
s1, preparing 60L of inositol feed liquid with the concentration of 50g/L, adding inositol oxidase to enable the concentration of system bacteria to reach 30OD, converting at 37 ℃ and pH=8 to obtain 64.5L of conversion liquid, adding 3.0L of chitosan solution into the conversion liquid for flocculation, filtering and collecting 71.2L of filtrate through a plate frame with the aperture of 50nm under the condition that the filtering pressure is 0.6MPa and the flow rate is 150L/h square meter, and filtering and collecting 78L of ultrafiltration membrane clear liquid through an ultrafiltration membrane;
s2, desalting the filtrate by 15L of cation exchange resin at a flow rate of 22L/h to obtain 82.2L of desalted liquid, wherein the conductivity of the desalted liquid is 6200us/cm;
s3, adding 3% of medicinal active carbon into the desalted liquid to decolorize, and collecting decolorized liquid after decolorization;
s4, concentrating the decolorized solution at 70 ℃ and-0.09 MPa to obtain 4.4L of concentrated solution with 62% of solid content;
s5, adding 4.4L glacial acetic acid into the concentrated solution to carry out a lactonization reaction at 60 ℃, after 6 hours of reaction, steaming out 2.1L of acid water at 60 ℃ and a vacuum degree of-0.09 MPa, and then carrying out dynamic gradient cooling crystallization at a speed of 8 ℃/h, wherein the crystallization termination temperature is 9 ℃. The crystallization mixture is filtered by suction to obtain 2.4kg of crude glucurolactone (white crystalline particles), the purity is 98.2% by liquid chromatograph, the crystallization yield is 81.49%, and the crude product can be used for subsequent refining.
Example 2
The embodiment provides a preparation method of glucurolactone, which comprises the following steps:
s1, preparing 60L of inositol feed liquid with the concentration of 50g/L, adding inositol oxidase to enable the concentration of system bacteria to reach 30OD, converting at 37 ℃ and pH=8 to obtain 63L of conversion liquid, filtering the conversion liquid by a ceramic membrane with the pore diameter of 50nm, collecting 72L of filtrate, and filtering the filtrate by an ultrafiltration membrane to collect 78L of ultrafiltration membrane clear liquid;
s2, desalting the filtrate by using 15L cation exchange resin at a flow rate of 22L/h to obtain a desalted solution 81L, wherein the conductivity of the desalted solution is 5800us/cm;
s3, adding 5% of medicinal active carbon into the desalted liquid for decolorization, and collecting decolorized liquid after decolorization;
s4, concentrating the decolorized solution at 60 ℃ and-0.09 MPa to obtain 4.3L of concentrated solution with the solid content of 50%;
s5, adding 4.2L of glacial acetic acid into the concentrated solution to carry out a lactonization reaction, wherein the lactonization reaction temperature is 50 ℃, after the reaction is carried out for 10 hours, steaming out 2L of acid water at the same temperature as the lactonization reaction and under the vacuum degree of minus 0.09MPa, then carrying out dynamic gradient cooling crystallization at the speed of 5 ℃/h, the crystallization termination temperature is 5 ℃, carrying out suction filtration on the crystallization mixture to obtain 2.38kg of a crude product (white crystalline particles) of glucurolactone, detecting the purity of the crude product to be 98.2% by a liquid chromatograph, and the crystallization yield to be 82.08%, wherein the crude product can be used for subsequent refining.
Example 3
The embodiment provides a preparation method of glucurolactone, which comprises the following steps:
s1, preparing 60L of inositol feed liquid with the concentration of 50g/L, adding inositol oxidase to enable the concentration of system bacteria to reach 30OD, converting at 37 ℃ and pH=8 to obtain 63L of conversion liquid, filtering the conversion liquid by a ceramic membrane with the pore diameter of 50nm, collecting 72L of filtrate, and filtering the filtrate by an ultrafiltration membrane to collect 78L of ultrafiltration membrane clear liquid;
s2, desalting the filtrate by 15L of cation exchange resin at a flow rate of 22L/h to obtain a desalted liquid 85L, wherein the conductivity of the desalted liquid is 6500us/cm;
s3, decolorizing the desalted liquid by using a 6L macroporous adsorption resin column, and collecting decolorized liquid after decolorization to obtain decolorized liquid 85L;
s4, concentrating the decolorized solution at 60 ℃ and-0.09 MPa to obtain 4.1L of concentrated solution with the solid content of 70%;
s5, adding 5L of glacial acetic acid into the concentrated solution to carry out a lactonization reaction, wherein the lactonization reaction temperature is 70 ℃, after 8 hours of reaction, 2L of acid water is distilled out under the same temperature as the lactonization reaction and the vacuum degree of minus 0.09MPa, then carrying out dynamic gradient cooling crystallization at the speed of 5 ℃/h, the crystallization termination temperature is 10 ℃, washing and drying the crystallization mixture by 2L of absolute ethyl alcohol to obtain 2.39kg of crude product of glucurolactone (white crystalline particles), the purity of which is detected by a liquid chromatograph is 98.2%, and the crystallization yield is 82.78%, wherein the crude product can be used for subsequent refining.
Example 4
The embodiment provides a preparation method of glucurolactone, which comprises the following steps:
s1, preparing 60L of inositol feed liquid with the concentration of 50g/L, adding inositol oxidase to enable the concentration of system bacteria to reach 30OD, converting at 37 ℃ and pH=8 to obtain 63L of conversion liquid, filtering the conversion liquid by a ceramic membrane with the pore diameter of 50nm, collecting 72L of filtrate, and filtering the filtrate by an ultrafiltration membrane to collect 78L of ultrafiltration membrane clear liquid;
s2, desalting the filtrate by using 15L cation exchange resin at a flow rate of 22L/h to obtain a desalted liquid 92L, wherein the conductivity of the desalted liquid is 5500us/cm;
s3, decolorizing the desalted liquid by using a 6L macroporous adsorption resin column, and collecting 97L decolorized liquid after decolorization;
s4, concentrating the decolorized solution at 80 ℃ and under the pressure of minus 0.09MPa to obtain 4.1L of concentrated solution with the solid content of 65%;
s5, adding 6L of glacial acetic acid into the concentrated solution to carry out a lactonization reaction, wherein the lactonization reaction temperature is 70 ℃, after the reaction is carried out for 5 hours, 2L of acid water is distilled out under the same temperature as the lactonization reaction and the vacuum degree of minus 0.09MPa, then carrying out dynamic gradient cooling crystallization at the speed of 7 ℃/h, the crystallization termination temperature is 15 ℃, washing and drying the crystallization mixture by 2L of absolute ethyl alcohol to obtain 2.4kg of crude products of glucurolactone (white crystalline particles), the purity of the crude products is detected to be 97.7% by a liquid chromatograph, the crystallization yield is 82.68%, and the crude products can be used for subsequent refining.
Example 5
The embodiment provides a preparation method of glucurolactone, which comprises the following steps:
s1, preparing 60L of 50g/L inositol feed liquid, adding inositol oxidase to enable the concentration of system bacteria to reach 30OD, converting at 37 ℃ and pH=8 to obtain 63L of conversion liquid, and filtering the conversion liquid by a ceramic membrane with the pore diameter of 50nm to collect 72L of filtrate; filtering the filtrate by an ultrafiltration membrane to collect 81L of ultrafiltration membrane clear liquid;
s2, desalting the ultrafiltration membrane filtrate by 15L of cation exchange resin at the flow rate of 22L/h to obtain a desalted liquid 92L, wherein the conductivity of the desalted liquid is 6300us/cm;
s3, decolorizing the desalted liquid by using a 6L macroporous adsorption resin column, and collecting 97L decolorized liquid after decolorization;
s4, concentrating the decolorized solution by a nanofiltration membrane at 80 ℃ and under the condition of minus 0.09MPa, collecting 23L of nanofiltration decolorized solution, and concentrating the nanofiltration decolorized solution to obtain 4.2L of concentrated solution with the solid content of 65%;
s5, adding 3.5L glacial acetic acid into the concentrated solution to carry out a lactonization reaction, wherein the lactonization reaction temperature is 50 ℃, after reacting for 10 hours, steaming out 2.1L acid water at the same temperature as the lactonization reaction and under the vacuum degree of 0.09MPa, then carrying out dynamic gradient cooling crystallization at the speed of 10 ℃/h, washing and drying the crystallization mixture by 2L absolute ethyl alcohol at the crystallization termination temperature of 9 ℃ to obtain 2.98kg of glucurolactone crude product (white crystalline particles), wherein the purity is 97.5 percent by a liquid chromatograph, the crystallization yield is 82.28 percent, and the crude product can be used for subsequent refining.
Comparative example 1
Compared with example 1, the equal volume and equal concentration glucuronic acid solution is prepared by a starch oxidation method after the inositol feed liquid is prefabricated, and other reaction conditions are unchanged.
Through testing, the purity of the finished product obtained under the reaction system is 78.6%, and the refining yield is 65.8%.
The reason is probably because the components of the glucuronic acid solution prepared by the starch oxidation method are different from those of the glucuronic acid solution prepared by inositol in the invention, and the process is not adapted to the process flow of the starch oxidation method under the condition of the same subsequent flow, so that the same technical effect cannot be achieved.
Comparative example 2
Compared with the embodiment 2, the ultrafiltration membrane filtration step is omitted, the ceramic membrane filtrate is directly desalted by ion exchange resin, and other reaction conditions are unchanged.
The purity of the finished product obtained under the reaction system under the condition is 88.4%, the crystallization yield is 61%, and the color of the finished product is visually different from that of the example 2.
The reason for this is presumably that, after the elimination of the ultrafiltration, impurities present in the solution cannot be removed effectively in the subsequent process until after crystallization are still present in the crude extract of glucurolactone, which reduces the purity of the product and causes a significant color difference.
Comparative example 3
In comparison with example 3, the solid content obtained in the concentration process was adjusted to 30%, and the other reaction conditions were unchanged.
The purity of the finished product obtained under the reaction system under the condition is 90.1 percent, and the crystallization yield is 21 percent.
The reason is presumably that the low solid content of the concentrate leads to high solubility of glucurolactone in the solution, which leads to a prolonged lactonization reaction time and an increase in byproducts, and thus, efficient crystallization is not possible.
Comparative example 4
In comparison with example 4, the vacuum distillation step in the lactonization crystallization step was omitted, and the other reaction conditions were unchanged.
The purity of the finished product obtained under the reaction system under the condition is 90.3 percent, and the crystallization yield is 16 percent.
The reason is presumably that the low solids content of the concentrate results in a higher solubility of the glucurolactone in the solution, resulting in excessive loss of the glucurolactone in water.
Comparative example 5
In comparison with example 5, the conductivity of the desalted liquid in step S2 was 8000us/cm by controlling the selection of the resin amount, and the other reaction conditions were unchanged.
The purity of the finished product obtained under the reaction system under the condition is 90.2%, and the crystallization yield is 56.7%.
Comparative example 6
Compared with the embodiment 5, the dynamic gradient cooling process in the step S5 is canceled, and the natural cooling is carried out instead, and other reaction conditions are unchanged.
The purity of the finished product obtained under the reaction system under the condition is 89.6 percent, and the crystallization yield is 40.5 percent.
* Test case
Further, the liquid chromatography test conditions in examples 1 to 5 of the present invention and comparative example 145 were as follows:
mobile phase: 10mmol/L formic acid aqueous solution;
chromatographic column: calcium column (300 x 7.7 or similar column);
flow rate: 0.5Ml/min;
a detector: a differential detector;
column temperature: 55 ℃;
detector temperature: 45 ℃;
solvent: 10mmol/L formic acid aqueous solution;
standard substance concentration: 1.0mg/mL (D-glucuronolactone [ CAS No. ] 32449-92-6, content of 99.9% based on C6H8O6, china food and drug inspection institute);
test sample concentration: 1.0mg/mL;
chromatographic conditions: run at 100% 10mmol/L aqueous formic acid for 30min.
The foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A method for preparing glucurolactone, which is characterized by comprising the following steps:
adding inositol oxidase into the inositol feed liquid to perform conversion to obtain conversion liquid;
the conversion solution is filtered to obtain filtrate,
the filtrate is subjected to ion exchange to obtain desalted liquid,
the desalted liquid is decolorized to obtain decolorized liquid,
the decolorized solution is thermally concentrated to obtain concentrated solution,
and (3) carrying out lactonization crystallization on the concentrated solution to obtain a crude product of the glucurolactone.
2. The method of claim 1, wherein the filtering comprises plate and frame filtering or ceramic membrane filtering; the aperture of the filter membrane for plate and frame filtration is 10-100nm; the separation pore diameter of the ceramic membrane is 20-100nm.
3. The method according to claim 1 or 2, wherein the ion exchange is performed with an ion exchange resin; the conductivity of the desalted liquid is less than 7000us/cm.
4. The method according to claim 1 or 2, wherein the means for decoloring comprises activated carbon decoloring or adsorbent resin decoloring; when the activated carbon is adopted for decolorization, the addition amount of the activated carbon is 1-5% of the mass of the desalted liquid.
5. The method of preparation according to claim 1 or 2, wherein the step of thermal concentration comprises: concentrating the decolorized solution to a concentrated solution with a solid content of 50-70%.
6. The method according to claim 1 or 2, wherein the step of lactonizing crystals comprises: and mixing the concentrated solution with glacial acetic acid to carry out a lactonization reaction, carrying out vacuum distillation after the reaction, and then cooling and crystallizing to obtain a crude product of glucurolactone.
7. The method according to claim 6, wherein the glacial acetic acid is added in an amount of 0.8 to 1.8 times the volume of the concentrated solution;
the temperature of the lactonization reaction is 50-70 ℃ and the reaction time is 5-10h;
the temperature of vacuum distillation is 50-70 ℃, the vacuum degree is-0.09 MPa, and the volume of the distilled product is 30-50% of the addition amount of glacial acetic acid;
the cooling crystallization is carried out at a rate of 5-10 ℃/h, and the crystallization termination temperature is 5-15 ℃.
8. The production method according to claim 1 or 2, characterized by further comprising, after the conversion solution is filtered to obtain a filtrate, before the filtrate is ion-exchanged to obtain a desalted solution: performing ultrafiltration membrane filtration on the filtrate to obtain ultra-clear filtrate; the aperture of the ultrafiltration membrane is 5000-20000Da.
9. The method according to claim 1 or 2, characterized by further comprising, after the desalting solution is decolorized to obtain a decolorized solution, before the decolorized solution is thermally concentrated to obtain a concentrated solution: concentrating the decolorized solution by using a nanofiltration membrane to obtain nanofiltration decolorized solution; the aperture of the nanofiltration membrane is 150-300Da, and the solid content of the nanofiltration decolorization liquid is 10-15%.
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| CN117467719A (en) * | 2023-10-30 | 2024-01-30 | 河北宇威生物科技有限公司 | Method for preparing glucurolactone by using enzyme-catalyzed starch |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117467719A (en) * | 2023-10-30 | 2024-01-30 | 河北宇威生物科技有限公司 | Method for preparing glucurolactone by using enzyme-catalyzed starch |
| CN117467719B (en) * | 2023-10-30 | 2024-05-31 | 河北宇威生物科技有限公司 | Method for preparing glucurolactone by using enzyme-catalyzed starch |
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