阅读说明：本技术 一种高纯度n-乙酰氨基葡萄糖的制备方法 (Preparation method of high-purity N-acetylglucosamine ) 是由 卢健行 刘长峰 马善丽 王庆 姚珊珊 于 2019-10-09 设计创作，主要内容包括：本发明属于医药化工领域,公开了一种高纯度N-乙酰氨基葡萄糖的制备方法。本发明高纯度N-乙酰氨基葡萄糖的制备方法包括以下步骤：(1)将甲壳素与氟化试剂、离子液体于超声波搅拌罐中溶解制得粗母液,再过滤制得精母液；(2)将步骤(1)制得的精母液与1-H-3-甲基咪唑硫酸氢盐离子液体混合制得降解液；(3)往降解液中加入活性炭脱色,过滤；(4)所得的滤液浓缩,降温,加入有机溶剂进行结晶,离心过滤得粗品；(5)将粗品用无水乙醇浸泡后搅拌过滤,干燥即得所述高纯度N-乙酰氨基葡萄糖。该方法制备的N-乙酰氨基葡萄糖纯度较高,且该方法工艺流程简单,成本较低,适合大规模的推广和应用。(The invention belongs to the field of pharmaceutical chemicals, and discloses a preparation method of high-purity N-acetylglucosamine. The preparation method of the high-purity N-acetylglucosamine comprises the following steps: (1) dissolving chitin, a fluoridation reagent and ionic liquid in an ultrasonic stirring tank to prepare a crude mother solution, and filtering to prepare a refined mother solution; (2) mixing the refined mother liquor prepared in the step (1) with 1-H-3-methylimidazole bisulfate ionic liquid to prepare degradation liquid; (3) adding activated carbon into the degradation liquid for decolorization, and filtering; (4) concentrating the obtained filtrate, cooling, adding an organic solvent for crystallization, and performing centrifugal filtration to obtain a crude product; (5) and soaking the crude product in absolute ethyl alcohol, stirring, filtering and drying to obtain the high-purity N-acetylglucosamine. The N-acetylglucosamine prepared by the method has high purity, and the method has simple process flow and low cost, and is suitable for large-scale popularization and application.)

1. A preparation method of high-purity N-acetylglucosamine is characterized by comprising the following steps:

(1) dissolving chitin, a fluorizating reagent and ionic liquid in an ultrasonic stirring tank to prepare a crude mother solution, and continuously pumping into a microporous membrane filter by using a diaphragm pump to filter to prepare a fine mother solution;

(2) mixing the refined mother liquor prepared in the step (1) with 1-H-3-methylimidazole bisulfate ionic liquid to prepare degradation liquid;

(3) adding 0.5 to 1.0 mass percent of active carbon of chitin into the degradation liquid prepared in the step (2) for decolorization, and filtering;

(4) concentrating the filtrate obtained in the step (3), cooling, adding an organic solvent into the concentrated solution for crystallization, and performing centrifugal filtration to obtain a crude product of the N-acetylglucosamine;

(5) and (4) soaking the crude product prepared in the step (4) in absolute ethyl alcohol, stirring, filtering and drying to obtain the high-purity N-acetylglucosamine.

2. The method for producing high purity N-acetylglucosamine according to claim 1, wherein the fluorinating agent used in the step (1) is hexafluoroisopropanol.

3. The method for preparing high-purity N-acetylglucosamine according to claim 1, wherein the ionic liquid in step (1) is one or a mixture of two of 1-butyl-3-methylimidazolium acetate and 1-butyl-3-methylimidazolium methyl sulfate; preferably, the volume ratio of the fluorinating agent to the ionic liquid in the step (1) is 1: 2-3; more preferably, the mass-to-volume ratio of the chitin to the fluorinating agent in the step (1) is 1: 0.5 to 1.

4. The method for preparing high-purity N-acetylglucosamine according to claim 1, wherein the volume ratio of the refined mother liquor to the 1-H-3-methylimidazolium hydrogen sulfate ionic liquid in the step (2) is 1: 1.5-2.5; preferably, the temperature of the mixed degradation reaction of the refined mother liquor and the 1-H-3-methylimidazole hydrogen sulfate ionic liquid in the step (2) is 65-80 ℃; more preferably, the refined mother liquor in the step (2) is mixed with 1-H-3-methylimidazole hydrogen sulfate ionic liquid and then is subjected to heat preservation reaction for 1-3 hours.

5. The method for producing high-purity N-acetylglucosamine according to claim 1, wherein the filtration in step (3) is performed by a microporous filter or an ultramicropore filter.

6. The method for producing high-purity N-acetylglucosamine according to claim 1, wherein the concentration of the filtrate in the step (4) is carried out by heating the filtrate to 70 to 90 ℃ under vacuum to concentrate the solution to a supersaturated state.

7. The method for producing high-purity N-acetylglucosamine according to claim 1, wherein the volume ratio of the concentrate to the organic solvent in step (4) is 1: 2 to 3.

8. The method for preparing high-purity N-acetylglucosamine according to claim 1, wherein the temperature reduction in the step (4) is carried out to 15 to 25 ℃.

9. The method for producing high-purity N-acetylglucosamine according to claim 1 or 7, wherein the organic solvent used in step (4) is an alcohol or ketone solvent, such as ethanol, absolute ethanol, propanol or acetone.

10. The method for producing high-purity N-acetylglucosamine according to claim 1, wherein the mass ratio of the crude product to the absolute ethanol in step (5) is 1: 2 to 3.

Technical Field

The invention relates to the field of pharmaceutical chemicals, and particularly relates to a preparation method of high-purity N-acetylglucosamine.

Background

Aminosugars are commonly used as monosaccharide residues in complex oligosaccharides and polysaccharides, glucosamine being an amino derivative of the monosaccharide glucose, and N-acetylglucosamine being an acetylated derivative of glucosamine. As a novel biochemical medicine, N-acetylglucosamine is a composition unit of various polysaccharides in a living body, particularly has the highest exoskeleton content in crustaceans, is a medicament for clinically treating rheumatic and rheumatoid arthritis, can also be used as a food antioxidant, an infant food additive and a sweetener for diabetics, can also be used for clinically enhancing the function of a human immune system, inhibiting the overgrowth of cancer cells or fiber cells and playing a role in inhibiting and treating cancers and malignant tumors.

The existing preparation method of N-acetylglucosamine mainly comprises the steps of preparing N-acetylglucosamine by a microbial fermentation method, preparing N-acetylglucosamine by a chemical method and preparing N-acetylglucosamine by enzymolysis. The preparation of N-acetylglucosamine by a microbial fermentation method needs to be carried out by the technical processes of microbial strain culture, fermentation, separation and the like, the whole technical process is complex, the operation is complicated, the yield is very low, the industrial production is not facilitated, the chemical method for producing N-acetylglucosamine needs a large amount of toxic and harmful chemical reagents in the preparation process, chemical residues exist in the product N-acetyl-D-glucosamine, chemical pollution is not beneficial to environmental protection, accidents such as combustion, explosion and the like are very easy to happen in the whole process, industrial cost needs to be increased no matter what enzyme is needed when N-acetylglucosamine is prepared by enzymolysis, the yield is also very low, the method is not beneficial to industrial production, and the three methods for preparing N-acetyl-D-glucosamine have the problems of low yield and low product purity. In view of the above-mentioned drawbacks, it is necessary to design a method for preparing high-purity N-acetylglucosamine.

Disclosure of Invention

The invention aims to overcome the defects of the background technology and provides a preparation method of high-purity N-acetylglucosamine, the N-acetylglucosamine prepared by the method has high purity, and the method has simple process flow and low cost, and is suitable for large-scale popularization and application.

In order to achieve the purpose of the invention, the preparation method of the high-purity N-acetylglucosamine comprises the following steps:

(1) dissolving chitin, a fluorizating reagent and ionic liquid in an ultrasonic stirring tank to prepare a crude mother solution, and continuously pumping into a microporous membrane filter by using a diaphragm pump to filter to prepare a fine mother solution;

(2) mixing the refined mother liquor prepared in the step (1) with 1-H-3-methylimidazole bisulfate ionic liquid to prepare degradation liquid;

(3) adding 0.5 to 1.0 mass percent of active carbon of chitin into the degradation liquid prepared in the step (2) for decolorization, and filtering;

(4) concentrating the filtrate obtained in the step (3), cooling, adding an organic solvent into the concentrated solution for crystallization, and performing centrifugal filtration to obtain a crude product of the N-acetylglucosamine;

(5) and (4) soaking the crude product prepared in the step (4) in absolute ethyl alcohol, stirring, filtering and drying to obtain the high-purity N-acetylglucosamine.

Further, the fluorinating agent in the step (1) is hexafluoroisopropanol.

Further, the ionic liquid in the step (1) is one or a mixture of two of 1-butyl-3-methylimidazole acetate and 1-butyl-3-methylimidazole methyl sulfate.

Preferably, the volume ratio of the fluorinating agent to the ionic liquid in the step (1) is 1: 2-3; more preferably, the mass-to-volume ratio of the chitin to the fluorinating agent in the step (1) is 1: 0.5 to 1.

Further, the volume ratio of the refined mother liquor to the 1-H-3-methylimidazole hydrogen sulfate ionic liquid in the step (2) is 1: 1.5 to 2.5.

Preferably, the temperature of the mixed degradation reaction of the refined mother liquor and the 1-H-3-methylimidazole hydrogen sulfate ionic liquid in the step (2) is 65-80 ℃.

More preferably, the refined mother liquor in the step (2) is mixed with 1-H-3-methylimidazole hydrogen sulfate ionic liquid and then is subjected to heat preservation reaction for 1-3 hours.

Further, the filtration in the step (3) is performed by a microporous filter or an ultramicropore filter.

Further, the filtrate concentration in the step (4) is to heat the filtrate to 70-90 ℃ under a vacuum condition, and concentrate the solution to a supersaturated state.

Further, the volume ratio of the concentrated solution to the organic solvent in the step (4) is 1: 2 to 3.

Further, the temperature reduction in the step (4) is to be carried out to 15-25 ℃.

Further, the organic solvent in step (4) is an alcohol or ketone solvent, such as ethanol, absolute ethanol, propanol or acetone.

Further, the mass ratio of the crude product to the absolute ethyl alcohol in the step (5) is 1: 2 to 3.

The preparation method uses the activated carbon as a decolorizing agent, and the activated carbon has strong adsorption performance, oxidation reduction performance and electrical performance due to the developed pore structure and the specific surface characteristic, and is often applied to water treatment.

Devitrification, which refers to the precipitation of another phase when a substance is in a non-equilibrium state, is a crystalline form. In the preparation method, the N-acetylglucosamine solution is concentrated to a supersaturated state, then the solution is cooled to 15-25 ℃, and an alcohol or ketone solvent, preferably an alcohol solvent, is added to crystallize the solution, so that the refined N-acetylglucosamine with high yield, good crystal form and high purity is obtained.

By the method, the N-acetylglucosamine preparation method has the advantages of less required equipment, simple process, easy post-treatment, low cost, recycled ethanol, environmental friendliness, economy and suitability for large-scale popularization and application, and the refined N-acetylglucosamine prepared by the preparation method has the purity of over 99.9 percent and high quality index, so that the available value of the N-acetylglucosamine in the pharmaceutical industry is greatly improved.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention. It is to be understood that the following description is only illustrative of the present invention and is not to be construed as limiting the present invention.

The terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

When an amount, concentration, or other value or parameter is expressed as a range, preferred range, or as a range of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when a range of "1 to 5" is disclosed, the described range should be interpreted to include the ranges "1 to 4", "1 to 3", "1 to 2 and 4 to 5", "1 to 3 and 5", and the like. When a range of values is described herein, unless otherwise stated, the range is intended to include the endpoints thereof and all integers and fractions within the range.