CN100420696C - Process for preparing refined N-acetyl-D-aminoglucose - Google Patents
Process for preparing refined N-acetyl-D-aminoglucose Download PDFInfo
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Abstract
The invention discloses a refining method of N-aceto-D-glucosamine in the resource and medical chemical technological domain, which comprises the following steps: A. decolouring; B. filtering; condensing; C. crystallizing; C. washing; drying; separating impurity through the following two physical methods: 1. adopting adsorbent to adsorb impurity and color in the product; 2. utilizing recrystallizing method of liquid-solid balancing relationship to refine.
Description
Technical field
The present invention relates to a kind of preparation method of glucose; In particular, the present invention relates to a kind of process for preparing refined N-acetyl-D-aminoglucose, belong to resource and pharmaceutical chemistry technical field
Background technology
N-acetyl-D-amino glucose, molecular formula are C
8H
15NO
6, it is the essentially consist unit of many important polysaccharide in the biological cell, especially the exoskeleton content with the marine organisms class is the highest.It is the special monose with higher sugariness, has reductibility, it also is the important as precursors of synthetic bifidus factor, have many important physiological function in vivo, be the medicine of treatment rheumatic and rheumatoid arthritis clinically, also can be used as food antioxidant and infant or baby food additive or diabetic subject's sweeting agent as Chinese patent application.It can strengthen human immune system's function simultaneously, the growth of anticancer, as the application of Chinese patent application (02126831.2) N-acetyl-D-amino glucose in preparing antitumor and anti metastasis, confirmed that by animal experimental data N-acetyl-D-amino glucose is inhibited in the growth of on one's body B16 tumour cell of mouse, PG tumour cell Biu tumour cell to grafting, N-acetyl-D-amino glucose can obviously suppress the growth of human liver cancer cell (SMMC-7721) in addition, to mouse S
180The tumour of sarcoma also has certain restraining effect.(people such as Zhang Li, the preliminary study of D-glucosamine and derivative anti-tumor activity thereof; Chinese Journal of Marine Drugs the 25th the 2nd phase of volume of April in 2006,26～31 pages) thus N-acetyl-D-amino glucose carninomatosis had suppress and therapeutic action.But the existing N-acetyl-D-amino glucose purity that buys from the market or develop is lower, can only reach about 99.33%, and multinomial quality index is all lower; For example, patent application WO97/31121 discloses a kind of method that is equipped with N-acetyl-D-amino glucose from the chitinase legal system, it is N-acetyl-D-chitosan with the acid hydrolysis of chitin part that Japanese patent application JP63273493 discloses a kind of, handle the glucose of the method preparation that obtains N-acetyl-D-amino glucose and adopt chemical synthesis with enzyme then, with GAH is raw material, diacetyl oxide is made acylating agent, the N-acetyl-D-amino glucose (He Xinyi etc., the development of N-acetyl-D-amino glucose that obtain by acylation reaction; 63～65 pages of Changde college of education journal (natural science edition) the 13rd the 4th phases of volume of December calendar year 2001).
Summary of the invention
Purpose of the present invention is exactly relatively poor in order to solve the existing purity of existing N-acetyl-D-amino glucose, and the technical problem that quality index is relatively poor proposes a kind of process for preparing refined N-acetyl-D-aminoglucose; This method not only can prepare the N-acetyl-D-amino glucose with higher degree, and its multinomial quality index all has raising in various degree; And this method technical process is simple, and cost is lower, is fit to large-scale promotion and application.
Technique scheme of the present invention is implemented by following technical problem: a kind of process for preparing refined N-acetyl-D-aminoglucose, and this method may further comprise the steps:
A, decolouring: the N-acetyl-D-amino glucose that will have preparation now, adds discoloring agent and decoloured 0.5～5 hour by stirring in water as material dissolution; Wherein the weight ratio of N-acetyl-D-amino glucose, water and discoloring agent is 1: 1.5～3: 0.01～0.1.
B, filtration, concentrated: filter by millipore filter or ultramicropore strainer through the solution after the decolouring with above-mentioned, filtrate filtered is added in the reactor, stir, stir heated solution to 50～80 ℃ under vacuum condition, back, solution is concentrated into hypersaturated state, wherein concentration time is 8～15 hours, and vacuum tightness is greater than 0.095MPa under the described vacuum condition;
C, crystallization: the solution after above-mentioned process concentrated is cooled to 0～10 ℃, adds organic solvent and carries out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 700～1500 rev/mins the whizzer centrifugal 15～60 minutes at rotating speed; Wherein the weight ratio as the N-acetyl-D-amino glucose of raw material is 5～20: 1 in organic solvent and the steps A;
D, bubble are washed, dried: the refined N-acetyl-D-aminoglucose work in-process after will be above-mentioned centrifugal are put to reactor, add organic solvent and steep and washes, and steep and carry out centrifugal 15～60 minutes after washing, and wherein the rotating speed of whizzer is 700～1500 rev/mins; Under temperature is 50～100 ℃ condition, dried 3～10 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product.
Preparation method of the present invention has adopted two kinds of methods in the physics method separating impurity, promptly 1. utilizes absorption principle to come separating impurity, adopts sorbent material that impurity in the product and color are adsorbed; 2. utilize the recrystallization method of liquid-solid equilibrium relationship in making with extra care.Can produce visible insolubles impurity in the process of common production N-acetyl-D-amino glucose or owing to controlling of production process pointer operation error makes N-acetyl-D-amino glucose become faint yellow, utilize discoloring agent (sorbent material) that wherein impurity and color are adsorbed totally among the present invention, obtain clear filtrate after filtration.
A kind of material is separated out crystallization from solution, first preparation supersaturated solution, method commonly used in the prior art has (1) with solution evaporation, be concentrated into do and highly finished product; (2) with after acid or the alkaline purification, the solubleness of the material of generation in water is very little, and then its concentration reaches hypersaturated state very soon and separates out crystallization.(3) in solution, add a kind of material (solid or liquid), the solubleness of solute is reduced and the formation supersaturated solution, thereby separate out crystallization; More than three kinds of resulting material masses of method relatively poor, among the preparation method of the present invention N-acetyl-D-amino glucose solution is concentrated into hypersaturated state, then solution is cooled off and the adding organic solvent, thereby make its crystallization obtain quality refined N-acetyl-D-aminoglucose preferably.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, be gac at the discoloring agent described in the steps A.Gac has flourishing pore structure and special surface property to be made it have extremely strong absorption property, redox property, electrical property usually to be applied in the water treatment, the present invention utilizes these performances of gac not only impurity such as water-fast arsenic salt, molysite, heavy metal in the N-acetyl-D-amino glucose solution to be had stronger adsorption function just, and, has removal effect preferably as materials such as colourity, odor smells to the organism that biological process and other method are difficult to remove.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, stirring velocity is 25～100 rev/mins in steps A.Not only production rate is fast but also help decolouring to adopt this stirring velocity.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, the mode by vacuum suction filter in step B filtrate filtered is added in the reactor.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, the time of stirring in step B is 8～15 hours, and stirring velocity is 10～60 rev/mins; Adopt this stirring velocity can make N-acetyl-D-amino glucose crystallization even.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, the solution temperature-fall period is after feeding 25 ℃ cooling water temperature to 25～35 ℃ in reacting kettle jacketing in step C, feeds the refrigerated water cooling 1～3 hour of zero degree again in the reacting kettle jacketing.The present invention filters the clear filtrate that the back forms by activated carbon decolorizing, and it is concentrated into hypersaturated state, and the cooling back adds organic solvent, thereby just can separate out pure white crystal.The present invention is in order to change the uneven situation of crystallographic dimension, can adopt earlier solution to be cooled after 25～35 ℃, again through 1～3 hour to 0～10 ℃ the method for refrigerated water cooling of zero degree, thereby obtains size nucleus comparatively uniformly.Can produce different crystal forms.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, be a kind of in ethanol, methyl alcohol, Virahol, the acetone at the organic solvent described in the step C.Because this crystal is insoluble to above-mentioned organic solvent, and the solubleness of water in these organic solvents is bigger, so this organic solvent extracting takes out the water in the N-acetyl-D-amino glucose solution, therefore uses these organic solvents to be used for yield height, the good crystalline of crystallisation process refined N-acetyl-D-aminoglucose.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, in step D, be used for steeping the organic solvent of washing and be a kind of of ethanol, formaldehyde, Virahol, acetone.Owing to this crystal is insoluble to above-mentioned organic solvent, can steep easily with these organic solvents to wash out remaining impurities or water in the refined N-acetyl-D-aminoglucose work in-process; Therefore the yield height, the good crystalline that use these organic solvents to be used to steep to wash the process refined N-acetyl-D-aminoglucose.
In above-mentioned process for preparing refined N-acetyl-D-aminoglucose, steep under stirring condition at the N-acetyl-D-amino glucose work in-process described in the step D and to wash, wherein the speed of Jiao Baning is 10～100 rev/mins, the time of stirring is 0.5～2 hour.
Influence the factor of crystalline form, the impurity as being mingled with in the pH value of crystallization velocity (speed of cooling), degree of supersaturation (temperature), solution or the solution all can influence crystalline form.The control of crystalline form is significant aborning.The crystalline form of the material that the crystallization method of available technology adopting obtains usually is needle-like and plate crystal, the crystal that is needle-like and plate crystal lumps than prism-shaped or granular being easy in storage process, simultaneously, needle-like and plate crystal granule mobile relatively poor causes the inconvenience of aspects such as operation, processing, conveying, packing.The refined N-acetyl-D-aminoglucose crystalline form of utilizing preparation method's preparation of the present invention is prism-shaped or thereby granular crystal has solved above-mentioned because the problem that aciculiform or sheet shape crystalline particle are caused.
In sum, process for preparing refined N-acetyl-D-aminoglucose of the present invention has the following advantages:
1, utilizes the refined N-acetyl-D-aminoglucose purity of preparation method's preparation of the present invention higher, reach more than 99.95%; Other quality index is all than common N-acetyl-D-amino glucose height; But improved its utility value in pharmaceutical industries greatly.
2, utilize the refined N-acetyl-D-aminoglucose crystal of preparation method's preparation of the present invention to be prism-shaped or granular crystal shape, not only be easy to store, and flowing property is better, be convenient to operation, processing, conveying, packing.
3, the technological process of process for preparing refined N-acetyl-D-aminoglucose of the present invention is simple, and preparation cost is lower, and required equipment is less; Be fit to large-scale promotion and application.
Embodiment:
Below make specific embodiments of the invention, technical scheme of the present invention is further described, but the present invention is not limited to these embodiment.
Embodiment 1:
One: the preparation of common N-acetyl-D-amino glucose:
With the D-glucosamine hydrochloride is raw material; diacetyl oxide is an acylating agent; getting tri-n-butylamine is dissolved in the ethanol; wherein the mol ratio of tri-n-butylamine and diacetyl oxide is 1: 4 o'clock; solution system is to react 1～2 hour under 9～10 the condition at pH value; acylation reaction generates in the polar solvent pyridine, makes common N-acetyl-D-amino glucose through a series of purification process.
Two: the preparation of refined N-acetyl-D-aminoglucose
With the common N-acetyl-D-amino glucose 200kg of above-mentioned preparation as material dissolution in the 400kg pure water, add 6kg discoloring agent gac and stirred 5 hours, stirring velocity is 25 rev/mins, decolours 5 hours;
Filter by millipore filter or ultramicropore strainer through the solution after the decolouring above-mentioned, filtrate filtered by vacuum suction filter to reactor, stirred 15 hours, the speed that stirs is 10 rev/mins, stir the back vacuum tightness be greater than the vacuum condition of 0.095MPa under heated solution to 50 ℃, solution is concentrated into hypersaturated state, and wherein concentration time is 15 hours;
Solution after above-mentioned process concentrated is put into crystallization kettle, feed 25 ℃ cooling water temperature to 35 ℃ in the chuck after, feed the refrigerated water cooling 1 hour to 10 ℃ of zero degree again, add organic solvent ethanol 2000kg and carry out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 700 rev/mins the whizzer centrifugal 60 minutes at rotating speed;
Above-mentioned refined N-acetyl-D-aminoglucose work in-process after centrifugal are put to reactor, adding organic solvent ethanol 200kg steeps under condition of stirring N-acetyl-D-amino glucose work in-process and washes, wherein the speed of Jiao Baning is 60 rev/mins, the refined N-acetyl-D-aminoglucose work in-process that bubble was washed after 0.5 hour carried out centrifugal 15 minutes, and wherein the rotating speed of whizzer is 1500 rev/mins; Under temperature is 50 ℃ condition, dried 10 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product; The crystal of prepared refined N-acetyl-D-aminoglucose finished product is prism-shaped or granular crystal body.
Embodiment 2
One: the preparation process of common N-acetyl-D-amino glucose is with embodiment 1:
Two: the preparation of refined N-acetyl-D-aminoglucose
With the common N-acetyl-D-amino glucose 500kg of above-mentioned preparation as material dissolution in the 1500kg pure water, add 50kg discoloring agent gac and stirred 3 hours, stirring velocity is 50 rev/mins, decolours 3 hours;
Filter by millipore filter or ultramicropore strainer through the solution after the decolouring above-mentioned, filtrate filtered by vacuum suction filter to reactor, stirred 12 hours, the speed that stirs is 20 rev/mins, stir the back vacuum tightness be greater than the vacuum condition of 0.095MPa under heated solution to 60 ℃, solution is concentrated into hypersaturated state, and wherein concentration time is 12 hours;
Solution after above-mentioned process concentrated is put into crystallization kettle, feed in the chuck 25 ℃ water coolant (in) be cooled to 25 ℃ after, feed the refrigerated water cooling 2 hours to 5 ℃ of zero degree again, add organic solvent ethanol 2500kg and carry out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 1000 rev/mins the whizzer centrifugal 45 minutes at rotating speed;
Above-mentioned refined N-acetyl-D-aminoglucose work in-process after centrifugal are put to reactor, adding organic solvent ethanol 500kg steeps under condition of stirring N-acetyl-D-amino glucose work in-process and washes, wherein the speed of Jiao Baning is 60 rev/mins, the refined N-acetyl-D-aminoglucose work in-process that bubble was washed after 1 hour carried out centrifugal 30 minutes, and wherein the rotating speed of whizzer is 1000 rev/mins; Under temperature is 60 ℃ condition, dried 8 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product; The crystal of prepared refined N-acetyl-D-aminoglucose finished product is prism-shaped or granular crystal body.
Embodiment 3
One: the preparation process of common N-acetyl-D-amino glucose is with embodiment 1:
Two: the preparation of refined N-acetyl-D-aminoglucose
With the common N-acetyl-D-amino glucose 400kg of above-mentioned preparation as material dissolution in the 600kg pure water, add 10kg discoloring agent gac and stirred 1 hour, stirring velocity is 75 rev/mins, decolours 1 hour;
Filter by millipore filter or ultramicropore strainer through the solution after the decolouring above-mentioned, filtrate filtered by vacuum suction filter to reactor, stirred 10 hours, the speed that stirs is 40 rev/mins, stir the back vacuum tightness be greater than the vacuum condition of 0.095MPa under heated solution to 70 ℃, solution is concentrated into hypersaturated state, and wherein concentration time is 10 hours;
Solution after above-mentioned process concentrated is put into crystallization kettle, feed 25 ℃ cooling water temperature to 28 ℃ in the chuck after, feed the refrigerated water cooling 2.5 hours to 3 ℃ of zero degree again, add organic solvent ethanol 8000kg and carry out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 1500 rev/mins the whizzer centrifugal 30 minutes at rotating speed;
Above-mentioned refined N-acetyl-D-aminoglucose work in-process after centrifugal are put to reactor, adding organic solvent ethanol 400kg steeps under condition of stirring N-acetyl-D-amino glucose work in-process and washes, wherein the speed of Jiao Baning is 60 rev/mins, the refined N-acetyl-D-aminoglucose work in-process that bubble was washed after 1.5 hours carried out centrifugal 45 minutes, and wherein the rotating speed of whizzer is 700 rev/mins; Under temperature is 80 ℃ condition, dried 5 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product; The crystal of prepared refined N-acetyl-D-aminoglucose finished product is prism-shaped or granular crystal body.
Embodiment 4
One: the preparation process of common N-acetyl-D-amino glucose is with embodiment 1:
Two: the preparation of refined N-acetyl-D-aminoglucose
With the common N-acetyl-D-amino glucose 300kg of above-mentioned preparation as material dissolution in the 600kg pure water, add 30kg discoloring agent gac and stirred 30 minutes, stirring velocity is 100 rev/mins, decolours 0.5 hour;
Filter by millipore filter or ultramicropore strainer through the solution after the decolouring above-mentioned, filtrate filtered by vacuum suction filter to reactor, stirred 8 hours, the speed that stirs is 60 rev/mins, stir the back vacuum tightness be greater than the vacuum condition of 0.095MPa under heated solution to 80 ℃, solution is concentrated into hypersaturated state, and wherein concentration time is 8 hours;
Solution after above-mentioned process concentrated is put into crystallization kettle, feed 25 ℃ cooling water temperature to 30 ℃ in the chuck after, feed the refrigerated water cooling 3 hours to 0 ℃ of zero degree again, add organic solvent ethanol 3000kg and carry out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 700 rev/mins the whizzer centrifugal 15 minutes at rotating speed;
Above-mentioned refined N-acetyl-D-aminoglucose work in-process after centrifugal are put to reactor, adding organic solvent ethanol 300kg steeps under condition of stirring N-acetyl-D-amino glucose work in-process and washes, wherein the speed of Jiao Baning is 60 rev/mins, the refined N-acetyl-D-aminoglucose work in-process that bubble was washed after 2 hours carried out centrifugal 60 minutes, and wherein the rotating speed of whizzer is 700 rev/mins; Under temperature is 100 ℃ condition, dried 3 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product; The crystal of prepared refined N-acetyl-D-aminoglucose finished product is prism-shaped or granular crystal body.
The refined N-acetyl-D-aminoglucose of the present invention's preparation and the quality index of common N-acetyl-D-amino glucose compare, and that compares the results are shown in Table shown in 1:
Table 1: the quality index comparative result of two kinds of N-acetyl-D-amino glucose
| Test item | Common N-acetylglucosamine detected result | Refining N-acetylglucosamine detected result |
| Purity | ≥99.33 | ≥99.95 |
| Proterties | White or micro-yellow powder | White crystal |
| Specific optical rotation | 42.15° | 40.29° |
| PH value | 7.3 | 7.02 |
| Arsenic salt | ≤1PPM | ≤0.5PPM |
| Molysite | ≤4PPM | ≤1PPM |
| Heavy metal | ≤8PPM | ≤2PPM |
| Weight loss on drying | ≤0.49％ | ≤0.02％ |
| Residue on ignition | ≤0.03％ | ≤0.01％ |
| Fusing point | 196.0℃-200.0℃ | 200.0℃-204.0℃ |
| Chlorion | ≤0.15％ | ≤0.01％ |
| Transmittance | ≥93％ | ≥97％ |
| Density | 0.28g/cm 3 | 0.43g/cm 3 |
Contrast as can be seen from every data data of table 1: utilize the every quality index of refined N-acetyl-D-aminoglucose of preparation method's preparation of the present invention all will improve a lot, but this has improved utility value greatly in pharmaceutical industries than the every quality index of common N-acetyl-D-amino glucose before refining.
Specific embodiment described in the present invention only is that the present invention's spirit is illustrated.The technician of the technical field of the invention can make various modifications or replenishes or adopt similar mode to substitute described specific embodiment, but can't depart from spirit of the present invention or surmount the defined scope of appended claims.
Although the present invention has been made detailed explanation and has quoted some specific exampless as proof, to those skilled in the art, only otherwise leave that the spirit and scope of the present invention can be done various variations or correction is obvious.
Claims (7)
1. process for preparing refined N-acetyl-D-aminoglucose, this method may further comprise the steps:
A, decolouring: the N-acetyl-D-amino glucose that will have preparation now, adds discoloring agent and decoloured 0.5～5 hour by stirring in water as material dissolution; Wherein the weight ratio of N-acetyl-D-amino glucose, water and discoloring agent is 1: 1.5～3: 0.01～0.1;
B, filtration, concentrated: filter by millipore filter or ultramicropore strainer through the solution after the decolouring with above-mentioned, filtrate filtered is added in the reactor, stir, stir heated solution to 50～80 ℃ under vacuum condition, back, solution is concentrated into hypersaturated state, wherein concentration time is 8～15 hours, and vacuum tightness is greater than 0.095MPa under the described vacuum condition;
C, crystallization: the solution after above-mentioned process concentrated is cooled to 0～10 ℃, adds organic solvent and carries out crystallization; N-acetyl-D-amino glucose crystal after the crystallization is in 700～1500 rev/mins the whizzer centrifugal 15～60 minutes at rotating speed; Wherein the weight ratio as the N-acetyl-D-amino glucose of raw material is 5～20:1 in organic solvent and the steps A, and described organic solvent is a kind of in ethanol, methyl alcohol, Virahol, the acetone;
D, bubble are washed, dried: the refined N-acetyl-D-aminoglucose work in-process after will be above-mentioned centrifugal are put to reactor, add organic solvent and steep and washes, and steep and carry out centrifugal 15～60 minutes after washing, and wherein the rotating speed of whizzer is 700～1500 rev/mins; Under temperature is 50～100 ℃ condition, dried 3～10 hours then, oven dry postcooling to room temperature promptly gets the refined N-acetyl-D-aminoglucose finished product, wherein is used for steeping the organic solvent of washing and is a kind of of ethanol, formaldehyde, Virahol, acetone.
2. N-acetyl-D-amino glucose preparation method according to claim 1 is characterized in that, is gac at the discoloring agent described in the steps A.
3. N-acetyl-D-amino glucose preparation method according to claim 1 and 2 is characterized in that stirring velocity is 25～100 rev/mins in steps A.
4. N-acetyl-D-amino glucose preparation method according to claim 1 and 2 is characterized in that the mode by vacuum suction filter in step B filtrate filtered is added in the reactor.
5. N-acetyl-D-amino glucose preparation method according to claim 1 and 2 is characterized in that the time of stirring is 8～15 hours in step B, stirring velocity is 10～60 rev/mins.
6. N-acetyl-D-amino glucose preparation method according to claim 1 and 2, it is characterized in that, the solution temperature-fall period is after feeding 25 ℃ cooling water temperature to 25～35 ℃ in reacting kettle jacketing in step C, feeds the refrigerated water cooling 1～3 hour of zero degree again in the reacting kettle jacketing.
7. N-acetyl-D-amino glucose preparation method according to claim 1 and 2, it is characterized in that, steep under stirring condition at the N-acetyl-D-amino glucose work in-process described in the step D and to wash, wherein the speed of Jiao Baning is 10～100 rev/mins, and the time of stirring is 0.5～2 hour.
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| CN102492001A (en) * | 2011-12-15 | 2012-06-13 | 石狮市华宝海洋生物化工有限公司 | Method for preparing N-acetyl-D-(+)-glucosamine |
| CN103509064A (en) * | 2012-06-18 | 2014-01-15 | 扬州明增生物科技有限公司 | N-acetyl-D-glucosamine production method |
| CN102866235B (en) * | 2012-10-15 | 2014-12-24 | 江苏澳新生物工程有限公司 | Detection method for D-glucosamine sulfate |
| CN106831895B (en) * | 2017-01-19 | 2019-11-01 | 山东润德生物科技有限公司 | A method of purifying N-acetylglucosamine |
| CN106946954A (en) * | 2017-03-29 | 2017-07-14 | 江苏澳新生物工程有限公司 | A kind of preparation method of N acetyl D Glucosamines |
| CN108383883A (en) * | 2018-04-09 | 2018-08-10 | 大自然生物集团有限公司 | The preparation method of high purity N-acetyl-D Glucosamines |
| CN110845552A (en) * | 2019-11-22 | 2020-02-28 | 山东润德生物科技有限公司 | Preparation method of acylated derivative of glucosamine |
| CN113912656A (en) * | 2021-09-30 | 2022-01-11 | 上海玉曜生物医药科技有限公司 | Crystal form of N-acetyl-D-glucosamine and preparation method and application thereof |
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