阅读说明：本技术 一种d-氨基葡萄糖盐酸盐的合成方法 (Synthesis method of D-glucosamine hydrochloride ) 是由 张孟涛 杨武涛 封浪 李旭峰 刘晓东 刘永超 马辉 于 2019-09-12 设计创作，主要内容包括：本发明涉及一种D-氨基葡萄糖盐酸盐的合成方法,属于生物工程技术领域,包括超滤、碳脱、浓缩、酸化、浓缩出粗品、粗品精制等步骤,首先将发酵液用硫酸或其他无机酸调节pH后过膜去除颗粒杂质、微生物菌体和部分大分子可溶性蛋白,其次通过活性炭吸附去除部门小分子蛋白质、核酸、色素、多肽等杂质,再次对上述碳脱液进行浓缩得到乙酰氨糖浓缩液并向浓缩液中加入适量工业浓盐酸进行酸化水解,酸化水解液进一步浓缩、育晶、过滤得盐酸氨糖粗品,最后盐酸氨糖粗品进行重溶、碳脱、浓缩、过滤等得到医药级或食品级盐酸氨糖。该工艺制得的盐酸氨糖纯度较高,工艺简单且生产过程中酸化用盐酸量较较传统工艺至少减少一半,环保压力大大减轻。(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.)

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:

regulating the pH value of N-acetyl-D-glucosamine fermentation liquor to 1.0 ~ 5.5.5 by using inorganic acid, and removing thalli and insoluble substances by using a ceramic membrane or a tubular membrane to obtain membrane filtration clear liquid;

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 a D-glucosamine hydrochloride solution, wherein the adding amount of the hydrochloric acid is that N-acetyl-D-glucosamine is HCl = 1: 1.2 ~ 1.5.5 according to a molar ratio, the temperature of acidification and 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 ~ 750g/L, cooling to 10 ~ 30 ℃ for crystal cultivation for 2 ~ 4 hours, and filtering to obtain a crude product of the D-glucosamine hydrochloride;

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.

2. The method for synthesizing D-glucosamine hydrochloride according to claim 1, wherein the method comprises the following steps: the inorganic acid in the first step is sulfuric acid, nitric acid or phosphoric acid.

3. The method for synthesizing D-glucosamine hydrochloride according to claim 1, wherein the method comprises the following steps: step one, the pH is adjusted to 2.0-4.0 by using inorganic acid.

4. The method for synthesizing D-glucosamine hydrochloride as defined in claim 1, wherein the pore size of the ceramic membrane or tubular membrane in step one is 10 ~ 100 nm.

5. The method for synthesizing D-glucosamine hydrochloride as recited in claim 1, wherein the concentration of said re-dissolution in step six is 150 ~ 350g/L, and the carbon addition amount for said carbon removal is 1 ~ 5% of the D-glucosamine hydrochloride content.

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 C6H13NO 5& 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:

regulating the pH value of N-acetyl-D-glucosamine fermentation liquor to 1.0 ~ 5.5.5 by using inorganic acid, and removing thalli and insoluble substances by using a ceramic membrane or a tubular membrane to obtain membrane filtration clear liquid;

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 a D-glucosamine hydrochloride solution, wherein the adding amount of the hydrochloric acid is that N-acetyl-D-glucosamine is HCl = 1: 1.2 ~ 1.5.5 according to a molar ratio, the temperature of acidification and 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 ~ 750g/L, cooling to 10 ~ 30 ℃ for crystal cultivation for 2 ~ 4 hours, and filtering to obtain a crude product of the D-glucosamine hydrochloride;

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 above scheme, in the first step, the pore diameter of the ceramic membrane or tubular membrane is 10 ~ 100nm

As a further optimization of the scheme, the concentration of the re-dissolution in the step six is 150 ~ 350g/L, the carbon adding amount of the carbon removal is 1 ~ 5 percent 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 fermentation liquor, adjusting the pH value to 5.0 ~ 5.5.5 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 is 400g/L, adding industrial hydrochloric acid (based on effective HCl) which is 1.5 times of the total mass of the acetamido in the concentrated liquor for acidification and hydrolysis, carrying out acid-protected hydrolysis at the temperature of 75 ℃ for 6H, evaporating and concentrating the hydrolyzed liquor until the concentration of the material liquor is 700g/L (based on the total mass of the acetamido temporarily) to obtain an ammoniac hydrochloride concentrated liquor, cooling and crystallizing the concentrated ammoniac hydrochloride liquor, filtering to obtain a crude product of the ammoniac hydrochloride, carrying out re-dissolving, carbon-removing, concentrating, crystallizing, filtering, drying and other refinements on the crude product of the ammoniac hydrochloride to obtain a finished product of the ammoniac hydrochloride, wherein the yield.

Example 2

Taking 10L (the content is 140 g/L) of the acetamido fermentation liquor, adjusting the pH value to 3.0 ~ 3.5.5 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 is 500g/L, adding industrial hydrochloric acid (based on effective HCl) which is 1.2 times of the total mass of the acetamido in the concentrated liquor for acidification and hydrolysis, carrying out acid-protected hydrolysis at the temperature of 80 ℃ for 6H, evaporating and concentrating the hydrolyzed liquor until the concentration of the material liquor is 600g/L (based on the total mass of the acetamido temporarily) to obtain an ammoniac hydrochloride concentrated liquor, cooling and crystallizing the concentrated ammoniac hydrochloride liquor, filtering to obtain a crude product of the ammoniac hydrochloride, carrying out re-dissolving, carbon-removing, concentrating, crystallizing, filtering, drying and other refinements on the crude product of the ammoniac hydrochloride to obtain a finished product of the ammoniac hydrochloride, wherein the yield.

Example 3

Taking 10L (the content is 140 g/L) of the acetamido fermentation liquor, adjusting the pH value to 3.0 ~ 3.5.5 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 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 liquor for acidification and hydrolysis, carrying out acidification and hydrolysis at 70 ℃, carrying out hydrolysis time of 6H, evaporating and concentrating the hydrolyzed liquor to 700g/L (based on the total mass of the acetamido temporarily) to obtain an ammoniacal sugar hydrochloride concentrated liquor, cooling and crystallizing the ammoniacal sugar hydrochloride concentrated liquor, and filtering to obtain an ammoniacal sugar hydrochloride crude product, carrying out re-dissolving, carbon desorption, concentration, crystal growing, filtering, drying and other refinements on the ammoniacal sugar crude product to obtain the finished product of the ammoniacal sugar hydrochloride, wherein the yield is 85%, and the 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.