阅读说明：本技术 一种n-乙酰氨基葡萄糖的制备方法 (Preparation method of N-acetylglucosamine ) 是由 卢健行 刘长峰 张建华 卢建功 吴祥舟 韩宁 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N-乙酰氨基葡萄糖的制备方法。本发明N-乙酰氨基葡萄糖的制备方法包括以下步骤：将甲壳素与乳酸甘氨酸盐酸盐、六氟异丙醇溶解制得粗母液,再使用微孔膜过滤器过滤制得精母液；将精母液与1-丙基璜酸基-3-甲基咪唑硫酸氢盐离子液体混合制得降解液；往降解液中加入活性炭脱色,过滤；滤液浓缩,降温,加入有机溶剂结晶,过滤得N-乙酰氨基葡萄糖粗品,用无水乙醇浸泡后搅拌过滤,干燥即得所述N-乙酰氨基葡萄糖。通过本发明方法制备的N-乙酰氨基葡萄糖收率高,所得N-乙酰氨基葡萄糖纯度可以达到99.9％以上,且该制备方法工艺简单,成本较低,所使用的溶剂可以回收利用,环保经济,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 N-acetylglucosamine. The preparation method of the N-acetylglucosamine comprises the following steps: dissolving chitin, glycine lactate hydrochloride and hexafluoroisopropanol to obtain a crude mother liquor, and filtering by using a microporous membrane filter to obtain a refined mother liquor; mixing the refined mother liquor with 1-propylsulfonic acid-3-methylimidazole bisulfate ionic liquid to prepare degradation liquid; adding activated carbon into the degradation liquid for decolorization, and filtering; concentrating the filtrate, cooling, adding an organic solvent for crystallization, filtering to obtain a crude product of N-acetylglucosamine, soaking in absolute ethanol, stirring, filtering, and drying to obtain the N-acetylglucosamine. The N-acetylglucosamine prepared by the method has high yield, the purity of the obtained N-acetylglucosamine can reach more than 99.9 percent, the preparation method has simple process and lower cost, the used solvent can be recycled, and the method is environment-friendly, economic and suitable for large-scale popularization and application.)

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

(1) dissolving chitin, glycine lactate hydrochloride and hexafluoroisopropanol in an ultrasonic stirring tank to obtain a crude mother liquor, and continuously pumping into a microporous membrane filter by using a diaphragm pump for filtering to obtain a refined mother liquor;

(2) mixing the refined mother liquor prepared in the step (1) with 1-propylsulfonic acid-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 N-acetylglucosamine according to claim 1, wherein the volume ratio of lactic acid glycine hydrochloride to hexafluoroisopropanol in the step (1) is 1 to 2: 1; preferably, the mass-to-volume ratio of the chitin to the glycine lactate hydrochloride in the step (1) is 1: 1 to 2.

3. The method for preparing N-acetylglucosamine according to claim 1, wherein the volume ratio of the refined mother liquor to the ionic liquid of 1-propylsulindyl-3-methylimidazole hydrogen sulfate in the step (2) is 1: 1-2; preferably, the temperature of the mixed degradation reaction of the refined mother liquor and the 1-propylsulfonic acid group-3-methylimidazole hydrogen sulfate ionic liquid in the step (2) is 72-85 ℃.

4. The method for preparing N-acetylglucosamine according to claim 1, wherein the refined mother liquor obtained in step (2) is mixed with 1-propylsulfo-3-methylimidazolium hydrogen sulfate ionic liquid and then subjected to a reaction under a heat preservation condition for 4-5 hours.

5. The process according to claim 1, wherein the filtration in the step (3) is carried out by a microporous filter or an ultramicropore filter.

6. The method for producing N-acetylglucosamine according to claim 1, wherein the concentration of the filtrate in the step (4) is carried out by heating the filtrate to 75 to 95 ℃ under vacuum to concentrate the solution to a supersaturated state.

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

8. The method for preparing N-acetylglucosamine according to claim 1, wherein the temperature reduction in the step (4) is to be 19-27 ℃.

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

10. The method for preparing N-acetylglucosamine according to claim 1, wherein the mass ratio of the crude product to the absolute ethyl alcohol in the 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 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 microbial fermentation method for preparing the N-acetylglucosamine needs to be subjected to microbial strain culture, then fermentation, separation and other technological processes, the whole technological process is complex, the operation is complex, the yield is very low, and the industrial production is not facilitated, the chemical method for producing the N-acetylglucosamine needs a large amount of toxic and harmful chemical reagents in the preparation process, not only chemical residues exist in the product of the N-acetylglucosamine, but also chemical pollution is not facilitated for environmental protection, accidents such as combustion, explosion and the like are easy to occur in the whole process, the N-acetylglucosamine is prepared by enzymolysis, the industrial cost needs to be increased no matter what kind of enzyme is needed, the yield is also very low, and the industrial production is not facilitated, and the three methods for preparing the N-acetylglucosamine 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 N-acetylglucosamine.

Disclosure of Invention

The invention aims to overcome the defects of the background technology and provides the preparation method of the N-acetylglucosamine, the method has simple process and lower cost, and the N-acetylglucosamine prepared by the method has higher yield and purity and good economic benefit and is suitable for large-scale popularization and application.

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

(1) dissolving chitin, glycine lactate hydrochloride and hexafluoroisopropanol in an ultrasonic stirring tank to obtain a crude mother liquor, and continuously pumping into a microporous membrane filter by using a diaphragm pump for filtering to obtain a refined mother liquor;

(2) mixing the refined mother liquor prepared in the step (1) with 1-propylsulfonic acid-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 N-acetylglucosamine.

Preferably, the volume ratio of the glycine lactate hydrochloride to the hexafluoroisopropanol in the step (1) is 1-2: 1; more preferably, the mass-to-volume ratio of the chitin to the glycine lactate hydrochloride in the step (1) is 1: 1 to 2.

Further, the volume ratio of the refined mother liquor to the 1-propylsulfonic acid-3-methylimidazole bisulfate ionic liquid in the step (2) is 1: 1 to 2.

Further, the temperature of the mixed degradation reaction of the refined mother liquor and the 1-propylsulfonic acid group-3-methylimidazole hydrogen sulfate ionic liquid in the step (2) is 72-85 ℃.

Further, mixing the refined mother liquor in the step (2) with 1-propylsulfonic acid-3-methylimidazole bisulfate ionic liquid, and then carrying out heat preservation reaction for 4-5 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 75-95 ℃ 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 19-27 ℃.

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.

Devitrification, which refers to the precipitation of another phase when a substance is in a non-equilibrium state, is a crystalline form. In order to purify a substance by crystallization, conditions suitable for a reaction system, such as temperature, solvent and the like, need to be selected, and the invention discovers that according to the preparation method, refined N-acetylglucosamine with high yield, good crystal form and high purity can be obtained by concentrating an N-acetylglucosamine solution to a supersaturated state, cooling the solution to 19-27 ℃, adding an alcohol or ketone solvent, preferably an alcohol solvent, and crystallizing the solution, wherein the purity or the yield of the obtained N-acetylglucosamine is not as high as 19-27 ℃ when the temperature is reduced to below 19 or above 27 ℃.

By the method, the yield of the N-acetylglucosamine prepared by the preparation method is high, the purity of the obtained N-acetylglucosamine can reach more than 99.9%, the preparation method is simple in process and low in cost, the used solvent can be recycled, and the preparation method is environment-friendly, economical and suitable for large-scale popularization and application.

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.