CN113248553A - Preparation method of D-glucosamine hydrochloride - Google Patents
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Abstract
The invention relates to a preparation method of D-glucosamine hydrochloride. Belongs to the technical field of biological engineering, and comprises the following specific steps: firstly, obtaining a N-acetylglucosamine clear solution; putting the N-acetylglucosamine into an ion exchange resin column for ion exchange to obtain a pure N-acetylglucosamine solution; then carrying out deacetylation reaction on the obtained product to obtain deacetylated clear liquid; adding hydrochloric acid to prepare D-glucosamine hydrochloride solution; carrying out evaporation concentration, cooling and filtration on the D-glucosamine hydrochloride solution; obtaining D-glucosamine hydrochloride crude crystals; dissolving, filtering and recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, collecting the crystal and drying; finally obtaining the pure D-glucosamine hydrochloride. The glucosamine hydrochloride prepared by the process has high purity, simple process, mild enzyme reaction conditions in the production process, less resin consumption and less waste hydrochloric acid discharge, and is an environment-friendly and efficient glucosamine production process.
Description
Technical Field
The invention belongs to the technical field of bioengineering, and particularly relates to a synthetic preparation method of D-glucosamine hydrochloride.
Background
Glucosamine (GlcNAc) is an important hexosamine formed by the substitution of one hydroxyl group of glucose with an amino group, readily soluble in water and hydrophilic solvents; widely existing in nature, chemical name is: 2-amino-2-deoxy-D-glucose is usually present in polysaccharides of microbial, animal origin and in conjugated polysaccharides in the form of N-acetyl derivatives, such as chitin, or N-sulfate esters and N-acetyl-3-O-lactate ether (muramic acid). Glucosamine hydrochloride, with a molecular weight of 215.5, is white crystal, odorless, slightly sweet, easily soluble in water, slightly soluble in methanol, and insoluble in organic solvents such as ethanol. Glucosamine is not itself very stable and is easily oxidized or degraded. Most are prepared into stable forms such as glucosamine hydrochloride, sulfate and phosphate.
In addition, the glucosamine has important physiological functions for human bodies, participates in liver and kidney detoxification, plays a role in resisting inflammation, protecting liver and tonifying kidney, has good curative effect on treating rheumatic arthritis and gastric ulcer, is a main raw material for synthesizing antibiotics and anticancer drugs, and can also be applied to food, cosmetics and feed additives.
Currently, there are three main types of GlcNAc production methods: chemical, enzymatic and microbiological methods; the chemical method can degrade chitin in shrimp and crab shells and fungal cell walls into glucosamine monomers by using high-concentration hydrochloric acid under certain conditions, but the severe damage to the environment caused by the severe reaction conditions due to the use of a large amount of concentrated hydrochloric acid is gradually limited by national policies, so that the deacetylation production process by adopting a mild reaction condition and an enzymatic method is more and more concerned; the enzymatic method is mainly characterized in that chitin is hydrolyzed by chitinase and deacetylase to obtain glucosamine monomers; the main raw materials of the extraction method are shrimp and crab shells and microbial fermentation liquor, and corresponding extraction processes need to be developed aiming at different raw materials. At present, the extraction method in the actual production process often has the defects of complex process route, low separation efficiency, high energy consumption, large environmental pollution and the like.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a novel preparation method of D-glucosamine hydrochloride.
The technical scheme is as follows: the preparation method of the D-glucosamine hydrochloride comprises the following specific operation steps:
(1.1), preparation of N-acetylglucosamine clear solution: adjusting the pH of the N-acetylglucosamine fermentation liquor which is subjected to high-density fermentation by engineering bacteria to weak acidity by using organic acid, adding chitin solution, performing flocculation and plate-frame filter pressing, and removing thalli and insoluble substances to obtain a clarified N-acetylglucosamine solution;
(1.2) preparation of pure N-acetylglucosamine solution: introducing the obtained N-acetylglucosamine clear solution into an ion exchange resin column for ion exchange, and removing soluble impurities and ash in the N-acetylglucosamine clear solution to obtain a pure N-acetylglucosamine solution;
(1.3) preparation of D-glucosamine hydrochloride solution: adding deacetylase into the obtained pure N-acetylglucosamine solution to carry out deacetylation reaction; performing membrane ultrafiltration on the N-acetylglucosamine solution subjected to deacetylation reaction by using an ultrafiltration membrane to remove enzyme protein in the solution and obtain deacetylated clear liquid; adding hydrochloric acid into the obtained clear liquid of the deacetylation reaction to prepare D-glucosamine hydrochloride solution;
(1.4) preparation of crude crystals of D-glucosamine hydrochloride: evaporating and concentrating the obtained D-glucosamine hydrochloride solution, cooling to 10-30 ℃, crystallizing for 2-6 hours, and filtering; thereby obtaining D-glucosamine hydrochloride crude crystals;
(1.5) preparation of pure D-glucosamine hydrochloride: dissolving, filtering and recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, collecting the crystal and drying; finally obtaining the pure D-glucosamine hydrochloride.
Further, in the step (1.1), the organic acid is glacial acetic acid, and the pH value of the weak acid is 4.0-5.9.
Further, in the step (1.1), the chitin is a natural polymeric flocculant compound, and the molecular weight of the chitin is 80-100 ten thousand Da.
Further, in the step (1.2), the resin in the ion exchange resin column comprises a strong acid cation resin and a macroporous anion weak base anion resin; the total content of the N-acetylglucosamine is 10-20%.
Further, in the step (1.3), the addition amount of the deacetylase is 1-5% (V/V) of the volume of the prepared pure N-acetylglucosamine solution; the enzyme activity of the deacetylase is 14-25U,
the deacetylation reaction conditions are as follows: the reaction temperature is 20-40 ℃; the pH value of the reaction process is controlled to be 6.5-7.5 by adding sodium hydroxide, and the reaction time is 30-60 min.
Further, in the step (1.3), the ultrafiltration membrane is one of a ceramic membrane and a tubular membrane, and the pore diameter of the membrane is 10-200 nm.
Further, in the step (1.3), the concentration of the added hydrochloric acid is 18% -42%, and the added hydrochloric acid is equal to the mol number of the glucosamine in the obtained clear liquid of the deacetylation reaction;
the prepared D-glucosamine hydrochloride solution is subjected to multi-effect vacuum concentration, the concentration temperature is 60-120 ℃, and the concentration of the glucosamine hydrochloride in the concentrated solution is 400-750 g/L.
Further, in the step (1.4), the mode of obtaining the D-glucosamine hydrochloride crude crystals is one of plate-and-frame filtration, vacuum filtration and centrifugation.
Further, in the step (1.5), the operation method of finally obtaining the pure D-glucosamine hydrochloride comprises the following steps: recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, firstly adding pure water into the coarse crystal according to the concentration of 300-600g/L, stirring, heating to 50-80 ℃ to dissolve the coarse crystal, and adding active carbon to decolor; wherein the using amount of the active carbon is 0.2-4% (W/V), the filtering temperature of the active carbon is 50-80 ℃, the temperature is reduced to 10-30 ℃, the glucosamine hydrochloride is recrystallized out, and the recrystallization is subjected to flash evaporation and drying, so that the pure D-glucosamine hydrochloride is prepared;
the content of the obtained pure D-glucosamine hydrochloride product is 98-105% by HPLC determination.
Further, mixing the crude D-glucosamine hydrochloride crystal (glucosamine crystallization mother liquor 1) and pure D-glucosamine hydrochloride (recrystallization mother liquor 2) for ion exchange, adsorbing glucosamine in the crystallization mother liquor through a strong acid cation exchange resin column, adsorbing acetic acid in the mother liquor through a weak base anion resin, and returning the lower column liquor to the step (1.3) for secondary enzyme deacetylation reaction, wherein the lower column liquor is an unreacted N-acetylglucosamine solution.
Has the advantages that: compared with the prior art, the invention has the beneficial effects that: 1. the process realizes the deacetylation enzyme by ultrafiltration membrane filtration, so that the enzyme and the product are effectively separated, the enzyme is recycled, and the use cost of the enzyme is reduced; 2. compared with the traditional glucosamine production process, on one hand, the byproduct sodium acetate and the incompletely reacted substrate are recycled, the conversion rate of the substrate is effectively improved, the dosage of the ion exchange resin and the consumption of the hydrochloric acid eluent are effectively reduced, and the triple benefits of low consumption, energy conservation and environmental protection are achieved; 3. compared with the coupling adsorption separation technology of the acetylglucosamine, the method has the advantages of mild reaction conditions, high reaction rate and energy conservation; 4. the method of the invention can be adopted to produce high-purity products more stably, and the product quality is more reliable; 5. the closed circulating operation process of triple-effect evaporation concentration, crystallization, continuous centrifugation and decoloration of the salt glucosamine is constructed, has the characteristics of high efficiency, energy conservation, low equipment investment and easily controlled sanitary conditions, and can form the potential of a set of continuous industrial production process and equipment facilities.
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FIG. 1 is a flow chart of the architecture of the present invention.
Detailed Description
The preparation method of the D-glucosamine hydrochloride comprises the steps of preparing N-acetylglucosamine fermentation clear liquid prepared by fermentation, hydrolyzing N-acetylglucosamine by deacetylase, preparing the glucosamine hydrochloride, and recycling mother liquor; the specific operation steps are as follows:
(1.1), preparation of N-acetylglucosamine clear solution: adjusting the pH of the N-acetylglucosamine fermentation liquor which is subjected to high-density fermentation by engineering bacteria to weak acidity by using organic acid, adding chitin solution, performing flocculation and plate-frame filter pressing, and removing thalli and insoluble substances to obtain a clarified N-acetylglucosamine solution;
(1.2) preparation of pure N-acetylglucosamine solution: introducing the obtained N-acetylglucosamine clear solution into an ion exchange resin column for ion exchange, and removing soluble impurities and ash in the N-acetylglucosamine clear solution to obtain a pure N-acetylglucosamine solution;
(1.3) preparation of D-glucosamine hydrochloride solution: adding deacetylase into the obtained pure N-acetylglucosamine solution to carry out (timing, constant temperature and constant) deacetylation reaction; performing membrane ultrafiltration on the N-acetylglucosamine solution subjected to deacetylation reaction by using an ultrafiltration membrane to remove enzyme protein in the solution and obtain deacetylated clear liquid; adding hydrochloric acid into the obtained clear liquid of the deacetylation reaction to prepare D-glucosamine hydrochloride solution;
(1.4) preparation of crude crystals of D-glucosamine hydrochloride: evaporating and concentrating the obtained D-glucosamine hydrochloride solution, gradually and slowly cooling to 10-30 ℃, and then carrying out crystal growth for 2-6 hours and filtering; thereby obtaining D-glucosamine hydrochloride crude crystals;
(1.5) preparation of pure D-glucosamine hydrochloride: dissolving, filtering and recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, collecting the crystal and drying; finally obtaining the pure D-glucosamine hydrochloride.
Further, in the step (1.1), the organic acid is glacial acetic acid, and the pH value of the weak acid is 4.0-5.9.
Further, in the step (1.1), the chitin is a natural polymeric flocculant compound, and the molecular weight of the chitin is 80-100 ten thousand Da.
Further, in the step (1.2), the resin in the ion exchange resin column comprises a strong acid cation resin and a macroporous anion weak base anion resin; the total content of the N-acetylglucosamine is 10-20%.
Further, in the step (1.3), the addition amount of the deacetylase is 1-5% (V/V) of the volume of the prepared pure N-acetylglucosamine solution; the enzyme activity of the deacetylase is 14-25U,
the deacetylation reaction conditions are as follows: the reaction temperature is 20-40 ℃; the pH value of the reaction process is controlled to be 6.5-7.5 by adding sodium hydroxide, and the reaction time is 30-60 min.
Further, in the step (1.3), the ultrafiltration membrane is one of a ceramic membrane and a tubular membrane, and the pore diameter of the membrane is 10-200 nm.
Further, in the step (1.3), the concentration of the added hydrochloric acid is 18% -42%, and the added hydrochloric acid is equal to the mol number of the glucosamine in the obtained clear liquid of the deacetylation reaction;
the prepared D-glucosamine hydrochloride solution is subjected to multi-effect vacuum concentration, the concentration temperature is 60-120 ℃, and the concentration of the glucosamine hydrochloride in the concentrated solution is 400-750 g/L.
Further, in the step (1.4), the mode of obtaining the D-glucosamine hydrochloride crude crystals is one of plate-and-frame filtration, vacuum filtration and centrifugation.
Further, in the step (1.5), the operation method of finally obtaining the pure D-glucosamine hydrochloride comprises the following steps: recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, firstly adding pure water into the coarse crystal according to the concentration of 300-600g/L, slowly stirring, heating to 50-80 ℃, gradually dissolving the coarse crystal, and adding activated carbon for decoloring; wherein the using amount of the active carbon is 0.2-4% (W/V), the filtering temperature of the active carbon is 50-80 ℃, the clear liquid is slowly cooled to 10-30 ℃ to recrystallize the glucosamine hydrochloride, and the recrystallization is subjected to flash evaporation and drying, so that a pure D-glucosamine hydrochloride product is prepared;
the content of the obtained pure D-glucosamine hydrochloride product is 98-105% by HPLC determination.
Further, mixing the crude D-glucosamine hydrochloride crystal (glucosamine crystallization mother liquor 1) and pure D-glucosamine hydrochloride (recrystallization mother liquor 2) for ion exchange, adsorbing glucosamine in the crystallization mother liquor through a strong acid cation exchange resin column, adsorbing acetic acid in the mother liquor through a weak base anion resin, and returning the lower column liquor to the step (1.3) for secondary enzyme deacetylation reaction, wherein the lower column liquor is an unreacted N-acetylglucosamine solution.
Example 1:
taking 100L (the content is 140g/L) of the acetamido sugar fermentation liquor, adding glacial acetic acid to adjust the pH value to 5.0, adding 2.5L of 4% chitin flocculant, standing for flocculation for 0.5h, and then carrying out plate-and-frame filter pressing; carrying out ion-exchange decoloration on the clear liquid obtained by plate-frame filter pressing to remove soluble protein organic matters and inorganic ash; adding 1L of deacetylase solution into 100L of ion exchange clear liquid, wherein the enzyme activity unit is 18U, the enzyme reaction temperature is 30 ℃, the reaction pH is 7.0 and is controlled by adding NaOH, the reaction time is 30min, and 0.4mol/L glucosamine can be generated; passing the enzyme reaction liquid through a tubular membrane with the aperture of 10nm, adding 4.0L of 36% hydrochloric acid into the obtained enzyme reaction clear liquid, uniformly stirring, carrying out vacuum concentration at 70 ℃ until the concentration of glucosamine hydrochloride is 500g/L, slowly stirring, cooling to 20 ℃, carrying out crystal growth for 2 hours, carrying out plate-and-frame filtration to collect glucosamine hydrochloride coarse crystals, carrying out refining on the coarse crystals such as re-dissolution, carbon desorption, concentration, crystallization, filtration, drying and the like to obtain an glucosamine hydrochloride finished product, separating and recycling glucosamine and acetamido in the crystallization mother liquid through an ion exchange column, wherein the yield of the glucosamine hydrochloride in the whole preparation process is 90%, and the content of the product is more than 98% by HPLC (high performance liquid chromatography).
Example 2:
taking 100L (the content is 140g/L) of the acetamido sugar fermentation liquor, adding glacial acetic acid to adjust the pH value to 4.5, adding 2.5L of 4% chitin flocculant, standing for flocculation for 0.5h, and then carrying out plate-and-frame filter pressing; carrying out ion-exchange decoloration on the clear liquid obtained by plate-frame filter pressing to remove soluble protein organic matters and inorganic ash; adding 5L of deacetylase solution with enzyme activity unit of 18U into 100L of ion exchange clear liquid, controlling the enzyme reaction temperature of 40 ℃ and the reaction pH of 7.0 by adding NaOH, and reacting for 30min to generate 0.4mol/L glucosamine; the enzyme reaction liquid passes through a ceramic membrane with the aperture of 100nm, 4.0L of 36% hydrochloric acid is added into the obtained enzyme reaction clear liquid, the mixture is uniformly stirred, vacuum concentration is carried out at 70 ℃ until the concentration of glucosamine hydrochloride is 700g/L, the mixture is slowly stirred, cooled to 10 ℃, crystallized for 2 hours, plate-frame filtration is carried out to collect glucosamine hydrochloride coarse crystals, the coarse crystals are refined through re-dissolution, carbon desorption, concentration, crystallization, filtration, drying and the like to obtain the glucosamine hydrochloride finished product, the glucosamine and the acetamido in the crystallization mother liquid are separated, recovered and reused through an ion exchange column, the yield of the glucosamine hydrochloride in the whole preparation process is 95%, and the content of the product is more than 98% through HPLC determination.
Example 3:
taking 100L (the content is 140g/L) of the acetamido sugar fermentation liquor, adding glacial acetic acid to adjust the pH value to 4.5, adding 2.5L of 4% chitin flocculant, standing for flocculation for 0.5h, and then carrying out plate-and-frame filter pressing; carrying out ion-exchange decoloration on the clear liquid obtained by plate-frame filter pressing to remove soluble protein organic matters and inorganic ash; adding 5L of deacetylase solution with enzyme activity unit of 20U into 100L of ion exchange clear liquid, controlling the reaction pH at 10 ℃ by adding NaOH, and reacting for 60min to generate 0.45mol/L glucosamine; and (2) passing the enzyme reaction liquid through a ceramic membrane with the aperture of 50nm, adding 4.5L of 36% hydrochloric acid into the obtained enzyme reaction clear liquid, uniformly stirring, carrying out vacuum concentration at 70 ℃ until the concentration of glucosamine hydrochloride is 700g/L, slowly stirring, cooling to 10 ℃, carrying out crystal growth for 2 hours, carrying out plate-and-frame filtration to collect glucosamine hydrochloride coarse crystals, carrying out refining on the coarse crystals such as re-dissolution, carbon desorption, concentration, crystallization, filtration, drying and the like to obtain an glucosamine hydrochloride finished product, separating and recycling glucosamine and acetamido in the crystallization mother liquid through an ion exchange column, wherein the yield of the glucosamine hydrochloride in the whole preparation process is 95%, and the content of the product is determined by HPLC and reaches more than 98%.
The invention relates to a novel preparation method of D-glucosamine hydrochloride, and the production process has the advantages of high conversion rate, high recovery rate, higher purity of the prepared glucosamine hydrochloride, simple process, mild enzyme reaction conditions in the production process, less resin consumption and less discharge of waste hydrochloric acid, and is an environment-friendly and efficient glucosamine production process.
Claims (9)
1. A preparation method of D-glucosamine hydrochloride is characterized by comprising the following specific operation steps:
(1.1), preparation of N-acetylglucosamine clear solution: adjusting the pH of the N-acetylglucosamine fermentation liquor which is subjected to high-density fermentation by engineering bacteria to weak acidity by using organic acid, adding chitin solution, performing flocculation and plate-frame filter pressing, and removing thalli and insoluble substances to obtain a clarified N-acetylglucosamine solution;
(1.2) preparation of pure N-acetylglucosamine solution: introducing the obtained N-acetylglucosamine clear solution into an ion exchange resin column for ion exchange, and removing soluble impurities and ash in the N-acetylglucosamine clear solution to obtain a pure N-acetylglucosamine solution;
(1.3) preparation of D-glucosamine hydrochloride solution: adding deacetylase into the obtained pure N-acetylglucosamine solution to carry out deacetylation reaction; performing membrane ultrafiltration on the N-acetylglucosamine solution subjected to deacetylation reaction by using an ultrafiltration membrane to remove enzyme protein in the solution and obtain deacetylated clear liquid; adding hydrochloric acid into the obtained clear liquid of the deacetylation reaction to prepare D-glucosamine hydrochloride solution;
(1.4) preparation of crude crystals of D-glucosamine hydrochloride: evaporating and concentrating the obtained D-glucosamine hydrochloride solution, cooling to 10-30 ℃, crystallizing for 2-6 hours, and filtering; thereby obtaining D-glucosamine hydrochloride crude crystals;
(1.5) preparation of pure D-glucosamine hydrochloride: dissolving, filtering and recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, collecting the crystal and drying; finally obtaining the pure D-glucosamine hydrochloride.
2. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein in step (1.1), the organic acid is glacial acetic acid, and the weakly acidic pH value is 4.0-5.9.
3. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein in step (1.1), the chitin is a natural polymeric flocculant compound with a molecular weight of 80-100 ten thousand Da.
4. The method according to claim 1, wherein in step (1.2), the resin in the ion exchange resin column comprises a strongly acidic cation resin and a macroporous anion weakly basic anion resin.
5. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein in the step (1.3), the amount of the deacetylase is 1-5% of the volume of the prepared pure N-acetylglucosamine solution;
the deacetylation reaction conditions are as follows: the reaction temperature is 20-40 ℃; the pH value of the reaction process is controlled to be 6.5-7.5 by adding sodium hydroxide, and the reaction time is 30-60 min.
6. The method according to claim 1, wherein in step (1.3), the ultrafiltration membrane is one of a ceramic membrane and a tubular membrane, and the pore size of the membrane is 10-200 nm.
7. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein in step (1.3), said hydrochloric acid is added in a concentration of 18% -42% in an amount equal to the molar number of the glucosamine in the obtained supernatant of the deacetylation reaction;
the prepared D-glucosamine hydrochloride solution is subjected to multi-effect vacuum concentration, the concentration temperature is 60-120 ℃, and the concentration of the glucosamine hydrochloride in the concentrated solution is 400-750 g/L.
8. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein in step (1.4), the crude D-glucosamine hydrochloride crystals are obtained by one of plate-and-frame filtration, vacuum filtration and centrifugation.
9. The method for preparing D-glucosamine hydrochloride according to claim 1, wherein the operation method for obtaining pure D-glucosamine hydrochloride in step (1.5) is: recrystallizing the obtained D-glucosamine hydrochloride coarse crystal, firstly adding pure water into the coarse crystal according to the concentration of 300-600g/L, stirring, heating to 50-80 ℃ to dissolve the coarse crystal, and adding active carbon to decolor; wherein the usage amount of active carbon is 0.2-2%, the filtering temperature of the active carbon is 50-80 ℃, the temperature is reduced to 10-30 ℃, the glucosamine hydrochloride is recrystallized out, and the recrystallization is subjected to flash evaporation and drying, so that the pure D-glucosamine hydrochloride is prepared;
the content of the obtained pure D-glucosamine hydrochloride product is 98-105% by HPLC determination.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113861247A (en) * | 2021-10-31 | 2021-12-31 | 扬州明增生物科技有限公司 | Method for extracting glucosamine hydrochloride from fermentation liquor |
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Application publication date: 20210813 |