CN104327128A - Preparation method of glucosamine hydrochloride - Google Patents
Preparation method of glucosamine hydrochloride Download PDFInfo
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- CN104327128A CN104327128A CN201410669251.9A CN201410669251A CN104327128A CN 104327128 A CN104327128 A CN 104327128A CN 201410669251 A CN201410669251 A CN 201410669251A CN 104327128 A CN104327128 A CN 104327128A
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- acetylglucosamine
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- glucosamine hydrochloride
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Abstract
The invention discloses a preparation method of glucosamine hydrochloride, which comprises the following steps: hydrolyzing acetylglucosamine with strong alkali, adding acid to neutralize into salt, decolorizing and filtering, concentrating for crystallization, centrifugating and drying to obtain the glucosamine hydrochloride. In the method, the hydrolyzed substrate is the single acetylglucosamine component, and the strong alkali is used instead of the traditional strong acid as the hydrolyzing reagent. The method has the advantages of high pertinence for hydrolysis reaction, small amount of required strong alkali, short hydrolysis reaction time, fewer side reactions, high product quality, high yield, low consumption of acid for acidification neutralization, and low pressure for labor protection and environmental protection, and is very suitable for demands of industrial production.
Description
Technical field
The present invention relates to the method for manufacturing of glucosamine hydrochloride, belong to field of medicaments.
Background technology
D-Glucosamine Hydrochloride (D-Glucosamine Hydrochloride, GAH), has another name called grape amine hydrochlorate, and formal name used at school is D-Glucosamine Hydrochloride, and molecular formula is: C
6h
13nO
5hCl, molecular weight 215.63, No. CAS: 66-84-2, structural formula is:
D-Glucosamine Hydrochloride is widely used in pharmaceutical synthesis, bacterial-infection resisting and immunological adjuvant, it is the activator of human body resisiting influenza virus, it can promote the synthesis of osteocyte protein-polysaccharide, improve the viscosity of knuckle synovia, improve metabolism of articular cartilage, effective treatment rheumatic arthritis, is therefore called " agent of OA amelioration of disease " by the world of medicine.Can be used as the nutritious subsidy agent of diabetic subject.A large amount of use is harmless to health.Amino acid-glucose and derivative have a wide range of applications in fields such as medical science, light industry, makeup.Pharmaceutically, as antibacterial-anti-inflammatory drug, be used for the treatment of rheumatism joint inflammation and treatment gastric ulcer, if use together with microbiotic, microbiotic absorption in blood can be promoted, reducing side reaction simultaneously also can the growth of anticancer, is the main raw material of synthesizing new anticarcinogen NSC-178248.In food, be the important micro-carbohydrate content of one that infant formulas Ruzhong is added, or the starting raw material of synthesis VB6 and riboflavin intermediate, can be applicable to again in addition in makeup and fodder additives, purposes is very extensive, and domestic and international demand increases all day by day.
It is the oven dry material that chitin dries material and citric acid waste that current industrial glucosamine hydrochloride produces the raw material usually adopted in all methods, two kinds of its water ratio of raw material all need to control below 10%, therefore no matter be that chitin dries material, or citric acid waste dries material all with special drying plant, and in drying course, uneven due to bake out temperature, can make effective constituent a large amount of in raw material be destroyed, even lose; The oven dry of material simultaneously also can produce oven dry cost.
Another main raw material of traditional mode of production glucosamine hydrochloride is concentrated hydrochloric acid, the object mainly hydrolysis salifying that concentrated hydrochloric acid uses.Usually, a lot of method takes high density to ensure the fast side reaction of hydrolysis reaction speed few, high quality concentrated hydrochloric acid is hydrolyzed.Even so, still there is more deficiency in this technique: in reaction process, concentration of hydrochloric acid is unstable, along with the carrying out of reaction, the concentration of hydrochloric acid is constantly successively decreased, and concentration of hydrochloric acid is lower, and hydrolysis reaction is more difficult to carry out, reaction time is longer, does not reach desirable reaction effect; Still occur (mainly the hydrolysis of nitrogen glycosidic bond easily occurring) with side reaction in hydrolytic process simultaneously, this adds increased subsequent purification difficulty, and affect end product quality, increase the problems such as manufacturing cost.
Summary of the invention
The object of this invention is to provide a kind of production method of glucosamine hydrochloride, the method not only wants rational technology, hydrolysis without side reaction, quality product and yield high, and hydrochloric acid usage quantity to be reduced, reduction labor protection and environmental pollution.
For realizing above-mentioned technical purpose, the production method of glucosamine hydrochloride of the present invention comprises the steps:
1) acetylglucosamine is dissolved in the water, then adds highly basic and heating and thermal insulation is hydrolyzed;
2) add in concentrated hydrochloric acid in hydrolyzed solution and salify, control ph 3 ~ 5;
3) hydrolyzed solution after neutralization is decoloured, concentrated;
4) by concentrated solution decrease temperature crystalline, be separated that to obtain glucosamine hydrochloride tide brilliant, drier finished product.
Above-mentioned steps 1) content of raw materials used acetylglucosamine answers >98%.Acetylglucosamine and purified water preferably mixs by weight 1: 4 ~ 6 (most preferably 1: 5), make acetylglucosamine fully be dissolved in water by stirring, then add highly basic and be hydrolyzed.Described highly basic is preferably KOH.In specific embodiments more of the present invention, KOH is mixed with the solution that mass percent concentration is 20 ~ 25%, be 1 ~ 1.5: 1 by the weight ratio of KOH solution and acetylglucosamine, KOH solution is added in acetylglucosamine solution, then be heated to 105 ~ 125 DEG C and carry out insulation hydrolysis, hydrolysis time is 2 ~ 3h.Final stopping hydrolysis judging according to acetylglucosamine transformation efficiency, could stop hydrolysis as the mass percent concentration <0.5% of acetylglucosamine.
Above-mentioned steps 2) use commercially available concentrated hydrochloric acid, concentration is 36 ~ 38%.The add-on of concentrated hydrochloric acid is step 1) 0.8 ~ 1.2 times of acetylglucosamine weight used.
Above-mentioned steps 3) add gac in hydrolyzed solution after acid neutralization, stirring heating is decoloured.Decolorization keeps temperature to be 60 ~ 65 DEG C, and the time is 0.5 ~ 1h.Activated carbon is preferably 767 needle-use activated carbons, and its consumption is step 1) acetylglucosamine weight used 10% ~ 20%.
Step 3) to filter after decolouring, filtrate carries out concentrating under reduced pressure, is preferably 70 ~ 80 DEG C in temperature, and pressure-controlling has been concentrated into crystal and has separated out under the condition of≤-0.08MPa.
Above-mentioned steps 4) in preferably take the crystallization of Temperature fall mode, then centrifugation goes out damp crystalline substance and carries out drying.Dry be preferably drying under reduced pressure, drying temperature 55-65 DEG C, pressure-controlling is at≤-0.08MPa.
The method preparing glucosamine hydrochloride provided by the invention, the substrate be hydrolyzed is the single main part of acetylglucosamine, and replaces traditional strong acid as hydrolysing agent with highly basic, and therefore, tool has the following advantages and positively effect:
1, hydrolysis reaction specificity is strong, and the reaction times is fast, and consumption hydrolysing agent is few;
2, produce without side reaction, substrate conversion efficiency is high, and product yield is good, and quality is high;
3, reaction end is easy to judge, subsequent processing steps is simple, is applicable to suitability for industrialized production;
4, acid adding amount is few, labor protection and environmental pollution little.
In sum, the preparation method of glucosamine hydrochloride provided by the invention is a kind of novel method with industrial value, can improve the quality of products and yield, there is again economic environmental protection, reduce the advantage of occupational hazards, be applicable to very much the actual needs of industrialized production.
Embodiment
Below by way of the description of embodiment, the invention will be further described, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, various amendment or improvement can be made, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
Embodiment 1:
(1) highly basic hydrolysis
Acetylglucosamine 100kg is added respectively successively in hydrolytic reaction pot, purified water 500kg, open and stir, the KOH solution that 100kg concentration is 20% is added again after acetylglucosamine is dissolved completely, abundant stirring, Heating temperature to 105 DEG C insulation, after 2h, acetylglucosamine transformation efficiency is observed in sampling, after 2.5h, acetylglucosamine mass percentage is down to 0.45%, stops hydrolysis.
(2) acid neutralization salify
In hydrolytic reaction pot, slowly add concentrated hydrochloric acid solution (36%-38%), open and stir, controlled hydrolysis liquid pH is 4.25, and concentrated hydrochloric acid consumption is about 100L.
(3) decolouring clarification
In the hydrolyzed solution after acid neutralization, add 20kg767 pin activated carbon, open and stir, filter after Heating temperature to 60 DEG C insulation 0.5h.
(4) concentrated
Be≤-0.08MPa by the filtrate after filtering at vacuum pressure, temperature is carry out concentrating under reduced pressure under 75 DEG C of conditions, is concentrated into the precipitation of adularescent xln.
(5) crystallization
The concentrated solution of adularescent xln is carried out Temperature fall crystallization.
(6) centrifugation
With whizzer, the glucosamine hydrochloride having tied crystalline substance is separated, obtains glucosamine hydrochloride tide brilliant.
(7) dry
Be≤-0.08MPa at vacuum pressure, temperature is carry out drying to separating glucosamine hydrochloride tide crystalline substance under 65 DEG C of conditions, obtains glucosamine hydrochloride finished product.
Embodiment 2:
(1) highly basic hydrolysis
Acetylglucosamine 100kg is added respectively successively in hydrolytic reaction pot, purified water 500kg, open and stir, the KOH solution that 120kg concentration is 20% is added again after acetylglucosamine is dissolved completely, abundant stirring, Heating temperature to 115 DEG C insulation, after 2h, acetylglucosamine transformation efficiency is observed in sampling, after 2.5h, acetylglucosamine mass percentage is down to 0.30%, stops hydrolysis.
(2) acid neutralization salify
In hydrolytic reaction pot, slowly add concentrated hydrochloric acid solution (36%-38%), open and stir, controlled hydrolysis liquid pH is 3.95, and concentrated hydrochloric acid consumption is about 115L.
(3) decolouring clarification
In the hydrolyzed solution after acid neutralization, add 20kg767 pin activated carbon, open and stir, filter after Heating temperature to 60 DEG C insulation 0.5h.
(4) concentrated
Be≤-0.08MPa by the filtrate after filtering at pressure, temperature is carry out concentrating under reduced pressure under 75 DEG C of conditions, is concentrated into the precipitation of adularescent xln.
(5) crystallization
The concentrated solution of adularescent xln is carried out Temperature fall crystallization.
(6) centrifugation
With whizzer, the glucosamine hydrochloride having tied crystalline substance is separated, obtains glucosamine hydrochloride tide brilliant.
(7) dry
Be≤-0.08MPa at vacuum pressure, temperature is carry out drying to separating glucosamine hydrochloride tide crystalline substance under 65 DEG C of conditions, obtains glucosamine hydrochloride finished product.
Embodiment 3:
(1) highly basic hydrolysis
Acetylglucosamine 100kg is added respectively successively in hydrolytic reaction pot, purified water 500kg, open and stir, the KOH solution that 150kg concentration is 20% is added again after acetylglucosamine is dissolved completely, abundant stirring, Heating temperature to 125 DEG C insulation, after 2h, acetylglucosamine transformation efficiency is observed in sampling, after 2h, acetylglucosamine mass percentage is down to 0.40%, stops hydrolysis.
(2) acid neutralization salify
In hydrolytic reaction pot, slowly add concentrated hydrochloric acid solution (36%-38%), open and stir, controlled hydrolysis liquid pH is 4.03, and concentrated hydrochloric acid consumption is about 135L.
(3) decolouring clarification
In the hydrolyzed solution after acid neutralization, add 20kg767 pin activated carbon, open and stir, filter after Heating temperature to 60 DEG C insulation 0.5h.
(4) concentrated
Be≤-0.08MPa by the filtrate after filtering at pressure, temperature is carry out concentrating under reduced pressure under 75 DEG C of conditions, is concentrated into the precipitation of adularescent xln.
(5) crystallization
The concentrated solution of adularescent xln is carried out Temperature fall crystallization.
(6) centrifugation
With whizzer, the glucosamine hydrochloride having tied crystalline substance is separated, obtains glucosamine hydrochloride tide brilliant.
(7) dry
Be≤-0.08MPa at vacuum pressure, temperature is carry out drying to separating glucosamine hydrochloride tide crystalline substance under 65 DEG C of conditions, obtains glucosamine hydrochloride finished product.
Claims (10)
1. a preparation method for glucosamine hydrochloride, comprises the following steps:
1) acetylglucosamine is dissolved in the water, then adds highly basic and heating and thermal insulation is hydrolyzed;
2) add in concentrated hydrochloric acid in hydrolyzed solution and salify, control ph 3 ~ 5;
3) hydrolyzed solution after neutralization is decoloured, concentrated;
4) by concentrated solution decrease temperature crystalline, be separated that to obtain glucosamine hydrochloride tide brilliant, drier finished product.
2. preparation method as claimed in claim 1, is characterized in that, step 1) content of raw materials used acetylglucosamine is greater than 98%.
3. preparation method as claimed in claim 1, is characterized in that, step 1) acetylglucosamine is mixed by weight 1: 4 ~ 6 with purified water, fully dissolve under stirring, then add highly basic, be heated to 105 ~ 125 DEG C of hydrolysis 2 ~ 3h.
4. preparation method as claimed in claim 3, is characterized in that, step 1) highly basic used to be mass percent concentration be 20 ~ 25% KOH solution, the KOH solution added and the weight ratio of acetylglucosamine are 1 ~ 1.5: 1.
5. preparation method as claimed in claim 1, is characterized in that, step 1) hydrolysis process is according to the judgement of acetylglucosamine transformation efficiency, and as the mass percent concentration <0.5% of acetylglucosamine, stopping is hydrolyzed.
6. preparation method as claimed in claim 1, is characterized in that, step 2) concentrated hydrochloric acid concentration used is 36 ~ 38%, its consumption is step 1) 0.8 ~ 1.2 times of acetylglucosamine weight used.
7. preparation method as claimed in claim 1, is characterized in that, step 3) use gac to decolour, bleaching temperature is 60 ~ 65 DEG C, and the time is 0.5 ~ 1h.
8. preparation method as claimed in claim 1, is characterized in that, step 3) to filter after decolouring, filtrate carries out concentrating under reduced pressure, is 70 ~ 80 DEG C in temperature, and pressure-controlling has been concentrated into crystal and has separated out under the condition of≤-0.08MPa.
9. preparation method as claimed in claim 1, is characterized in that, step 4) take the crystallization of Temperature fall mode.
10. preparation method as claimed in claim 1, is characterized in that, step 4) drying under reduced pressure is carried out to damp crystalline substance, drying temperature 55 ~ 65 DEG C, pressure-controlling is at≤-0.08MPa.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110305176A (en) * | 2019-06-28 | 2019-10-08 | 山东润德生物科技有限公司 | A kind of preparation method improving aminoglucose hydrochloride thermal stability |
| CN114681472A (en) * | 2019-03-13 | 2022-07-01 | 中国人民解放军军事科学院军事医学研究院 | Application of glucosamine and derivatives thereof as antiviral drugs |
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| WO2007123622A1 (en) * | 2006-03-31 | 2007-11-01 | Cargill, Incorporated | Glucosamine and n-acetylglucosamine compositions and methods of making the same from fungal biomass |
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| EP0732400A2 (en) * | 1995-03-13 | 1996-09-18 | Dirctor General Of The Agency Of Industrial Science And Technology | Process for producing N-acetyl-D-glucosamine deacetylase |
| CN1467227A (en) * | 2002-07-09 | 2004-01-14 | 邵建华 | Closed path circulation and comprehensive utilization for waste liquor of chitin and derivative production |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114681472A (en) * | 2019-03-13 | 2022-07-01 | 中国人民解放军军事科学院军事医学研究院 | Application of glucosamine and derivatives thereof as antiviral drugs |
| CN114681472B (en) * | 2019-03-13 | 2023-06-30 | 中国人民解放军军事科学院军事医学研究院 | Application of glucosamine and derivatives thereof as antiviral drugs |
| CN110305176A (en) * | 2019-06-28 | 2019-10-08 | 山东润德生物科技有限公司 | A kind of preparation method improving aminoglucose hydrochloride thermal stability |
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Application publication date: 20150204 |