CN110590867B - Synthesis method of D-glucosamine hydrochloride - Google Patents
Synthesis method of D-glucosamine hydrochloride Download PDFInfo
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- CN110590867B CN110590867B CN201910866958.1A CN201910866958A CN110590867B CN 110590867 B CN110590867 B CN 110590867B CN 201910866958 A CN201910866958 A CN 201910866958A CN 110590867 B CN110590867 B CN 110590867B
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- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
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Abstract
The invention relates to a method for synthesizing D-glucosamine hydrochloride, which belongs to the technical field of bioengineering and comprises the steps of ultrafiltration, carbon desorption, concentration, acidification, concentration to obtain a crude product, refining the crude product and the like. The glucosamine hydrochloride prepared by the process has high purity, the process is simple, the amount of hydrochloric acid for acidification in the production process is reduced by at least half compared with that of the traditional process, and the environmental protection pressure is greatly reduced.
Description
Technical Field
The invention belongs to the technical field of bioengineering, and particularly relates to a method for synthesizing D-glucosamine hydrochloride.
Background
Glucosamine hydrochloride, molecular formula C6H13NO5 & HCl, molecular weight 215.5, white crystal, NO smell, slight sweet taste, easy water solubility, slightly soluble in methanol, insoluble in organic solvent such as ethanol, etc., has important physiological function for human body, participates in liver and kidney detoxification, plays the role of anti-inflammation, liver protection and kidney tonifying, has good curative effect on treating rheumatic arthritis and gastric ulcer, is a main raw material for synthesizing antibiotics and anticancer drugs, and can be applied to food, cosmetics and feed additives. The commercial ammoniacal acetum sugar is obtained by acidifying and hydrolyzing acetamido sugar, and the current production method of the acetamido sugar mainly comprises a chemical method and a biological fermentation method, wherein the chemical method is mainly to obtain the acetamido sugar by hydrolyzing chitin, but the chitin produced by the chemical method is mainly derived from shells of shellfish animals, shrimp shells, crab shells and the like, the animals are influenced by the environment or seasons, some consumers allergic to seafood products cannot eat the animals, and meanwhile, the chemical method can also produce a large amount of waste water to cause certain pollution to the surrounding environment, so the development of the acetamido sugar produced by the chemical method is greatly limited. The production of the acetamido sugar by the biological fermentation method has the advantages of short production time, high yield, high efficiency, no limitation of seasons and regions on substrates, little pollution to the environment, microbial fermentation synthesis of products and avoidance of the phenomenon of allergy after the products are taken by consumers. Although the source of the acetamido sugar can be well solved by a biological fermentation method, a large amount of inorganic acid hydrochloric acid is used in the process of synthesizing the acetamido sugar hydrochloride, and the environmental impact is great.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide a method for synthesizing D-glucosamine hydrochloride.
In order to achieve the purpose, the invention adopts the specific scheme that:
a method for synthesizing D-glucosamine hydrochloride comprises the separation and extraction of N-acetyl-D-glucosamine and the acidification and hydrolysis of the N-acetyl-D-glucosamine, and comprises the following steps:
adjusting the pH value of the N-acetyl-D-glucosamine fermentation broth to 1.0-5.5 by using inorganic acid, and removing thalli and insoluble substances through a ceramic membrane or a tubular membrane to obtain a membrane filtration clear solution;
step two, performing activated carbon decoloration and impurity removal on the membrane filtration clear liquid obtained in the step one, wherein the mass of the activated carbon is 1-10% of the total content of the N-acetyl-D-glucosamine in the membrane filtration clear liquid, and the condition of activated carbon decoloration is as follows: the temperature is 30-90 deg.C, and the time is 20-120min to obtain decarbonization solution
Step three, evaporating and concentrating the decarbonization solution obtained in the step two to obtain an N-acetyl-D-glucosamine concentrated solution, wherein the concentration of the N-acetyl-D-glucosamine concentrated solution is 300-;
step four, adding hydrochloric acid into the N-acetyl-D-glucosamine concentrated solution obtained in the step three for acidification and hydrolysis to obtain D-glucosamine hydrochloride solution; the addition amount of the hydrochloric acid is as follows: according to the molar ratio, N-acetyl-D-glucosamine: HCl = 1: 1.2 to 1.5; the temperature of the acidification hydrolysis is 70-95 ℃, and the time is 1.5-6 hours;
step five, concentrating the D-glucosamine hydrochloride solution obtained in the step four to 400-750 g/L, cooling to 10-30 ℃, carrying out crystal growth for 2-4 hours, and filtering to obtain a D-glucosamine hydrochloride crude product;
and step six, refining the D-glucosamine hydrochloride crude product obtained in the step five by redissolving, decarbonizing, concentrating, crystallizing, filtering and drying to obtain a D-glucosamine hydrochloride finished product.
As a further optimization of the above scheme, in the first step, the inorganic acid is sulfuric acid, nitric acid or phosphoric acid.
As a further optimization of the above protocol, in step one, the pH is adjusted to 2.0-4.0 with a mineral acid.
As a further optimization of the scheme, in the step one, the aperture of the ceramic membrane or the tubular membrane is 10-100 nm
As a further optimization of the scheme, the concentration of the re-dissolution in the step six is 150-350 g/L, the carbon adding amount of the carbon removal is 1-5% of the content of the glucosamine hydrochloride,
has the advantages that:
1. compared with the traditional processes such as membrane passing, ion exchange, electrodialysis desalination and the like, the method provided by the invention has the advantages that the process is simpler, the equipment investment is less, and the large-scale production can be realized in a common factory;
2. in the separation and extraction stage of the N-acetyl-D-glucosamine, the method firstly adopts inorganic acid to adjust the pH value, and simultaneously reduces the use amount of industrial hydrochloric acid in the production process of the glucosamine hydrochloride by adding the inorganic acid as a catalyst, so that the acid use amount of the industrial hydrochloric acid in the acidification and hydrolysis step of the glucosamine hydrochloride is reduced by at least half compared with the acid use amount in the acidification of the traditional process, the later environmental protection pressure is greatly reduced, and the double effects of protecting the environment and improving the product quality are achieved.
3. Compared with the traditional process, the process is more stable, the purity of the product is higher, and the quality is more reliable.
Drawings
FIG. 1 is a process flow diagram of the process of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention.
Example 1
Taking 10L (the content is 140 g/L) of the acetamido sugar fermentation liquor, adjusting the pH value to 5.0-5.5 with concentrated sulfuric acid, passing through a ceramic membrane, adding activated carbon into the clear ceramic liquor for decolorization and impurity removal, then evaporating and concentrating the decarbonized liquor until the concentration of the acetamido sugar is 400g/L, adding industrial hydrochloric acid (based on effective HCl) which is 1.5 times of the total mass of the acetamido sugar in the concentrated liquor for acidification and hydrolysis, wherein the acidification and hydrolysis temperature is 75 ℃, and the hydrolysis time is 6H; evaporating and concentrating the hydrolyzed feed liquid to 700g/L (based on the total amount of the acetamido sugar temporarily) to obtain concentrated solution of the glucosamine hydrochloride, cooling the concentrated solution of the glucosamine hydrochloride, culturing crystals, and filtering to obtain crude product of the glucosamine hydrochloride; the glucosamine crude product is refined by redissolving, decarbonizing, concentrating, crystallizing, filtering, drying and the like to obtain a finished product of the glucosamine hydrochloride, the yield is 85 percent, and the product reaches the index of a pharmaceutical grade product.
Example 2
Taking 10L (the content is 140 g/L) of the acetamido sugar fermentation liquor, adjusting the pH value to 3.0-3.5 with concentrated sulfuric acid, passing through a ceramic membrane, adding activated carbon into the clear ceramic liquor for decolorization and impurity removal, then evaporating and concentrating the decarbonized liquor until the concentration of the acetamido sugar is 500g/L, adding industrial hydrochloric acid (based on effective HCl) which is 1.2 times of the total mass of the acetamido sugar in the concentrated liquor for acidification and hydrolysis, wherein the acidification and hydrolysis temperature is 80 ℃, and the hydrolysis time is 6H; evaporating and concentrating the hydrolyzed feed liquid to 600g/L (based on the total amount of the acetamido sugar temporarily) to obtain concentrated solution of the glucosamine hydrochloride, cooling the concentrated solution of the glucosamine hydrochloride, culturing crystals, and filtering to obtain crude product of the glucosamine hydrochloride; the glucosamine crude product is refined by redissolving, decarbonizing, concentrating, crystallizing, filtering, drying and the like to obtain a finished product of the glucosamine hydrochloride, the yield is 80 percent, and the product reaches the index of a pharmaceutical grade product.
Example 3
Taking 10L (the content is 140 g/L) of the acetamido fermentation liquor, adjusting the pH value to 3.0-3.5 with concentrated sulfuric acid, passing through a ceramic membrane, adding activated carbon into the clear ceramic liquid for decolorization and impurity removal, then evaporating and concentrating the decarbonized liquid until the concentration of the acetamido is 550g/L, adding industrial hydrochloric acid (based on effective HCl) which is 2.0 times of the total mass of the acetamido in the concentrated liquid for acidification and hydrolysis, wherein the acidification and hydrolysis temperature is 70 ℃, and the hydrolysis time is 6H; evaporating and concentrating the hydrolyzed feed liquid to 700g/L (based on the total amount of the acetamido sugar temporarily) to obtain concentrated solution of the glucosamine hydrochloride, cooling the concentrated solution of the glucosamine hydrochloride, culturing crystals, and filtering to obtain crude product of the glucosamine hydrochloride; the glucosamine crude product is refined by redissolving, decarbonizing, concentrating, crystallizing, filtering, drying and the like to obtain a finished product of the glucosamine hydrochloride, the yield is 85 percent, and the product reaches the index of a pharmaceutical grade product.
Comparative example 1 (comparative test relating to conventional Process)
Taking 10L (the content is 140 g/L) of the acetamido sugar fermentation liquor to pass through a ceramic membrane, adding activated carbon into the clear ceramic liquor to decolor and remove impurities, then carrying out evaporation concentration on the carbon-removed liquor after electrodialysis desalination until the concentration of the acetamido sugar is 450g/L, and adding industrial hydrochloric acid (based on effective HCl) which is 4.0 times of the total mass of the acetamido sugar in the concentrated liquor to carry out acidification hydrolysis, wherein the acidification hydrolysis temperature is 80 ℃, and the hydrolysis time is 12H; hydrolyzing to obtain concentrated solution of glucosamine hydrochloride, cooling, crystallizing, and filtering to obtain crude product of glucosamine hydrochloride; the glucosamine crude product is refined by redissolving, decarbonizing, concentrating, crystallizing, filtering, drying and the like to obtain a finished product of the glucosamine hydrochloride, the yield is 60 percent, and the product reaches the index of a pharmaceutical grade product.
Comparative example 2 (relevant case when pH of fermentation broth was adjusted without sulfuric acid)
Taking 10L (the content is 140 g/L) of the acetamido sugar fermentation liquor to pass through a ceramic membrane, adding activated carbon into the clear ceramic liquor to decolor and remove impurities, then evaporating and concentrating the decarbonized liquor until the concentration of the acetamido sugar is 550g/L, adding industrial hydrochloric acid (based on effective HCl) which is 2.0 times of the total mass of the acetamido sugar in the concentrated liquor to carry out acidification and hydrolysis, wherein the acidification and hydrolysis temperature is 80 ℃, and the hydrolysis time is 6H; evaporating and concentrating the hydrolyzed feed liquid to 700g/L (based on the total amount of the acetamido sugar temporarily) to obtain concentrated solution of the glucosamine hydrochloride, cooling the concentrated solution of the glucosamine hydrochloride, culturing crystals, and filtering to obtain crude product of the glucosamine hydrochloride; the glucosamine crude product is refined by redissolving, decarbonizing, concentrating, crystallizing, filtering, drying and the like to obtain a finished product of the glucosamine hydrochloride, the yield is 50 percent, and the product does not reach the index of a pharmaceutical grade product.
From the above results, it can be seen that: compared with the comparative example 1 (the traditional process), the process flow is shorter, the amount of acid used for acidification is less, the acidification time is shorter, and the yield is higher. Compared with comparative example 2, the invention proves that the addition of sulfuric acid can promote the acidification process of the acetamido sugar and play a role similar to a catalyst.
It should be noted that the above-mentioned embodiments illustrate rather than limit the scope of the invention, which is defined by the appended claims. It will be apparent to those skilled in the art that certain insubstantial modifications and adaptations of the present invention can be made without departing from the spirit and scope of the invention.
Claims (2)
1. A method for synthesizing D-glucosamine hydrochloride comprises the separation and extraction of N-acetyl-D-glucosamine and the acidification and hydrolysis of the N-acetyl-D-glucosamine, and is characterized in that: the method comprises the following steps:
adjusting the pH value of the N-acetyl-D-glucosamine fermentation broth to 5.0-5.5 by using inorganic acid, and removing thalli and insoluble substances through a ceramic membrane or a tubular membrane to obtain a membrane filtration clear solution; the inorganic acid is sulfuric acid;
step two, performing activated carbon decoloration and impurity removal on the membrane filtration clear liquid obtained in the step one, wherein the mass of the activated carbon is 1-10% of the total content of the N-acetyl-D-glucosamine in the membrane filtration clear liquid, and the condition of activated carbon decoloration is as follows: the temperature is 30-90 deg.C, and the time is 20-120min to obtain decarbonization solution;
step three, evaporating and concentrating the decarbonization solution obtained in the step two to obtain an N-acetyl-D-glucosamine concentrated solution, wherein the concentration of the N-acetyl-D-glucosamine concentrated solution is 300-;
step four, adding hydrochloric acid into the N-acetyl-D-glucosamine concentrated solution obtained in the step three for acidification and hydrolysis to obtain D-glucosamine hydrochloride solution; the addition amount of the hydrochloric acid is as follows: according to the molar ratio, N-acetyl-D-glucosamine: HCl = 1: 1.2 to 1.5; the temperature of the acidification hydrolysis is 70-95 ℃, and the time is 1.5-6 hours;
step five, concentrating the D-glucosamine hydrochloride solution obtained in the step four to 400-750 g/L, cooling to 10-30 ℃, carrying out crystal growth for 2-4 hours, and filtering to obtain a D-glucosamine hydrochloride crude product;
step six, refining the D-glucosamine hydrochloride crude product obtained in the step five by redissolving, decarbonizing, concentrating, crystallizing, filtering and drying to obtain a D-glucosamine hydrochloride finished product;
sixthly, the concentration of the re-dissolution is 150-350 g/L, and the carbon adding amount of the carbon removal is 1-5% of the content of the D-glucosamine hydrochloride.
2. The method for synthesizing D-glucosamine hydrochloride according to claim 1, wherein the method comprises the following steps: in the first step, the aperture of the ceramic membrane or the tubular membrane is 10-100 nm.
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| CN111111592A (en) * | 2020-01-03 | 2020-05-08 | 山东润德生物科技有限公司 | Circulating separation system based on ceramic membrane process |
| CN113045610B (en) * | 2020-12-20 | 2023-04-11 | 宁夏金维制药股份有限公司 | Method for extracting glucosamine from N-acetylglucosamine fermentation liquor |
| CN112608959B (en) * | 2020-12-31 | 2024-04-23 | 河南巨龙生物工程股份有限公司 | Method for improving fermentation unit of acetylglucosamine |
| CN112778384B (en) * | 2021-01-12 | 2022-11-25 | 山东润德生物科技有限公司 | Method for improving yield of glucosamine hydrochloride and application thereof |
| CN113248553A (en) * | 2021-06-07 | 2021-08-13 | 江苏海飞生物科技有限公司 | Preparation method of D-glucosamine hydrochloride |
| CN113956300A (en) * | 2021-11-12 | 2022-01-21 | 莱特莱德(上海)技术有限公司 | Preparation method of glucosamine hydrochloride |
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| USH2218H1 (en) * | 2002-03-05 | 2008-06-03 | Ki-Oh Hwang | Glucosamine and method of making glucosamine from microbial biomass |
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