CN106967131B - A kind of Glucosamine Sulphate product and preparation method thereof - Google Patents
A kind of Glucosamine Sulphate product and preparation method thereof Download PDFInfo
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- CN106967131B CN106967131B CN201710345968.1A CN201710345968A CN106967131B CN 106967131 B CN106967131 B CN 106967131B CN 201710345968 A CN201710345968 A CN 201710345968A CN 106967131 B CN106967131 B CN 106967131B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
- C07H5/06—Aminosugars
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Abstract
The present invention provides a kind of preparation methods of Glucosamine Sulphate, the described method includes: aminoglucose hydrochloride is configured to aqueous solution, the chloride ion in the aqueous solution is removed by anion exchange resin, it washs the property anion exchange resin and obtains glucosamine solution, sulfuric acid is added after concentration to react to obtain Glucosamine Sulphate solution, it is dry, obtain Glucosamine Sulphate.The present invention also provides the Glucosamine Sulphate products for using the method to be prepared, the purity of Glucosamine Sulphate is higher than 98% in the product, catabolite 2,5- fructosazine and 2,5- deoxy fructosazine content is lower than 0.5%, chloride ion content < 0.1%, sodium ions content < 0.01%, moisture < 1.0%.
Description
Technical field
The present invention relates to field of biological pharmacy, in particular to a kind of Glucosamine Sulphate product and its preparation side
Method.
Background technique
Glucosamine is the substance synthesized in human body, be in cartilage matrix necessary to synthetic proteins glycan it is important at
Part, it is the important nutrient to form cartilage cell, is the natural tissues composition of healthy articular cartilage.Glucosamine not only controls
The health of human body Bones and joints, also control the metabolic balance of articular cartilage synovial membrane.Glucosamine can largely expedite the emergence of for human body
Make joint part nimbly and freely so that constantly lubricating joint cartilage surface, reduction are worn with supplement knuckle synovia.It supplements enough
Knuckle synovia also provides for articular cartilage, enough material carriers.Glucosamine passes through strong impulse cartilage cell,
Collagen and hyaluronic acid in synthesized human constantly repair the articular cartilage being worn, and can generate new joint
Cartilage and synovial membrane, to restore the normal physiological function and helpless function of joint part.Meanwhile for taking anti-inflammatory for a long time
Analgesic drug and caused by articular chondrocytes damage, it may have good repair.Glucosamine is articular cavity
Interior " street cleaner " can not only inhibit the inflammatory reaction of nonspecific factor, release pain, and can eliminate harmful in articular cavity
Enzyme improves the immunity in joint and body.The raising that immunity is brought by supplementing Glucosamine is to eliminate arthritis
Important prerequisite.
With advancing age, the shortage of the intracorporal Glucosamine of people is increasingly severe, articular cartilage constantly degenerate and
Abrasion.A large amount of medical researches in the U.S., Europe and Japan show: Glucosamine can help to repair and safeguard cartilage, and energy
Stimulate the growth of cartilage cell.
Glucosamine for whole body articulate Osteoarthritis treatment and prevention: including knee joint, hip joint,
Backbone, shoulder, hand and wrist, ankle-joint etc..Glucosamine can directly act on the retrogression of arthritis knuckle cartilage, be to control
The effective and newtype drug for treating the Osteoarthritis cause of disease, can improve joint patient symptom and joint structure simultaneously, and ammonia is thought in research
Base glucose is the specific drug for treating Osteoarthritis, there is the pair of the anti-inflammatory pain-stopping effect of non-steroidal anti-inflammatory drugs and not damaged stomach
Effect, therapeutic effect are more preferable and more permanent.
Human body cartilage is mainly that " sulfate radical " is leaned on to mediate to the absorption of Glucosamine, and Glucosamine Sulphate then has
This " sulfate radical ".The joint important component of people contains " sulfate radical " (such as chondroitin sulfate) for containing " sulfate radical " together
Glucosamine Sulphate can seem and more " get close to ", absorb more preferable.
Currently, the Glucosamine of domestic listing has aminoglucose hydrochloride, Glucosamine Sulphate sodium chloride double salt, sulphur
Sour Glucosamine potassium chloride double salt and Glucosamine Sulphate monomer.Aminoglucose hydrochloride, Glucosamine Sulphate chlorination
Sodium double salt, Glucosamine Sulphate potassium chloride double salt contain a large amount of chloride ion, and research data shows that old man is most of often same
When suffer from cardiovascular disease or nephrosis, salt and cholesterol are the important substances of hypertension incidence.Further investigations have shown that in salt
Chloride ion be only one of important substance of hypertension incidence.Patient in view of Osteoarthritis is largely old man, and old man
It is most of often to suffer from cardiovascular disease and nephrosis, aminoglucose hydrochloride, Glucosamine Sulphate sodium chloride double salt, sulfuric acid simultaneously
Glucosamine potassium chloride double salt all contains chloride ion, and cardiovascular disease and nephrotic should not take more, therefore, sulfuric acid amino Portugal
Grape sugar monomer is to treat the ideal drug of old osteoarthritis.
To develop Glucosamine sulfuric acid mono-salt product, it has been disclosed that some prior arts:
Patent application 200810071617.7 discloses a kind of preparation method of Glucosamine Sulphate, its main feature is that with first
Shell element is raw material, then deacetylated under low-concentration sulfuric acid high temperature with concentrated sulfuric acid degradation chitin, miscellaneous through film sulfuric acid after filtering
Pure Glucosamine Sulphate solid is made in matter, decoloration concentration, drying.Its main feature is that directly carrying out de- second with low-concentration sulfuric acid
Acylated to generate Glucosamine Sulphate, the disadvantage is that treated, impurity is more, needs to remove unreacted by various membrane filter methods
The impurity and sulfuric acid that object, reaction generate need to use diffusive dialysis method and nano filtering process sulfuric acid, and purification process is complicated, and impurity is larger.
Patent application 201010176479.6 discloses the preparation method of high-purity D-glucosamine sulfate, its main feature is that
D-Glucosamine Hydrochloride of the purity not less than 95% is added in the alkaline solution under stirring, reaction, which is made, contains chloride
The mixed liquor of crystallization and free D- Glucosamine, desalting and filtering remove chloride, obtain the organic molten of free D- Glucosamine
Liquid is added dropwise sulfuric acid into salt, D- aminoglucose sulfate is obtained after purification.This method feature is in alkali organic solvent system
Hydrochloric acid is neutralized, the salt of the chloride of generation is insoluble in the system, removes by the method for filtering, the disadvantage is that Glucosamine exists
It is unstable under alkaline condition, be also easy to produce condensation reaction, generate foreign pigment, and it is insufficient to remove chloride, residual chloride ion compared with
It is more.
Patent application 201110142458.7 discloses a kind of preparation method of aminoglucose sulfate, feature
Be by the acidic ion liquid of chitosan and sulfur acid hydrogen salt hydrolysis 2~5 hours in water, then by active carbon decoloring,
It after concentration, is crystallized and is refined with organic solvent, Glucosamine Sulphate is made.The disadvantage is that very much (including the sun of impurity after reaction
Ion), a large amount of cation can not be contained by active carbon and organic solvent crystallization removal, Glucosamine Sulphate obtained,
For double salt product, purity is lower.
Patent application 201110263694.4 discloses a kind of new method for preparing Glucosamine Sulphate, its main feature is that with
Aminoglucose hydrochloride is raw material, its aqueous solution is handled by strong-base anion-exchange resin to remove its chloride ion and obtain
Glucosamine, then neutralize with sulfuric acid Glucosamine and obtain Glucosamine Sulphate, it then dries and obtains not sodium chloride-containing
Glucosamine Sulphate.Its drying means is using dry after directly freezed drying and solvent deposition.Using lacking for freeze-drying
Point is that Glucosamine Sulphate concentration is lower, in batches cannot be too big, and freeze drier energy consumption is big, is not easy large-scale production, and dry
Crystallization after dry is more loose, is not easy to crush；It is using disadvantage dry after solvent deposition, easily form grease and is not easy to disperse,
Yield is lower, dry difficult.
Patent application 201410458623.3 discloses a kind of preparation method of Glucosamine Sulphate, its main feature is that D- ammonia
Base glucose hydrochloride salt is distributed in alcoholic solvent, with alkali neutralization D-Glucosamine Hydrochloride, into D- glucosamine solution
Sulfuric acid is added dropwise into salt, after separation is precipitated, uses a small amount of organic solvent washing solid repeatedly, until be dried under reduced pressure after without chloride ion wash-off,
It is made.The disadvantage is that D-Glucosamine Hydrochloride dissolubility in alcoholic solvent is poor, dispersion is uneven, the bad control of pH in N-process
System, and in subsequent processes, the effect using solvent washing method removal sodium ion (or potassium ion) and chloride ion is poor, obtained
Still contain a large amount of metal ion and chloride ion in Glucosamine Sulphate.
In order to overcome the drawbacks of the prior art, the purity and crystal habit of Glucosamine Sulphate are further increased, and is dropped
Low energy consumption and yield propose the present invention.
Summary of the invention
The first object of the present invention is to provide a kind of preparation method of Glucosamine Sulphate, the preparation method energy
The high-purity sulfuric acid Glucosamine without harmful ion is obtained with very high yield.
The second object of the present invention is to provide a kind of high-purity sulfuric acid aminoglucose prepared using the method
Sugar product, the product are easy to crush, and moisture content is low, and stability is high, and sodium ion, potassium ion and chloride ion content are extremely low.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
One aspect of the present invention is related to a kind of preparation method of Glucosamine Sulphate, which comprises by amino
Glucosamine salt hydrochlorate is configured to aqueous solution, the chloride ion in the aqueous solution is removed by anion exchange resin, described in washing
Property anion exchange resin and obtain glucosamine solution, sulfuric acid is added after concentration and reacts to obtain Glucosamine Sulphate
Solution, it is dry, obtain Glucosamine Sulphate.
Aminoglucose hydrochloride is soluble easily in water, by being configured to aqueous solution, make its ionization be Glucosamine N+ sun from
Son and chloride ion, make chloride ion separate out.
The purpose of ion exchange is that after processing using strong basic anion-exchange resin, resin exists in the form of OH-,
It when aminoglucose hydrochloride aqueous solution passes through resin, is swapped with OH-, chloride ion and resin-bonded, OH- and amino Portugal
Grape sugar N+ cation, which combines, generates Glucosamine, and for Glucosamine in alkalinity, pH value is about 9.0~11.0.
Glucosamine is in alkalinity, after sulfuric acid is added, Glucosamine Sulphate is generated after neutralizing with sulfuric acid, in aqueous solution
With Glucosamine N+ cation and sulfate ion.
After moisture is steamed, Glucosamine Sulphate is precipitated, and becomes solid, then after being dried, obtains sulfuric acid amino Portugal
Grape sugar.
Preferably, the anion exchange resin is strong-base anion-exchange resin, it is preferable that the anion exchange
Resin is strong-base anion-exchange resin, it is preferable that the strong-base anion-exchange resin is selected from D201, D202, D203,
One of D301,201 × 4 and 201 × 7, preferably 201 × 7.
D201, D202, D203, D301,201 × 4 and 201 × 7 resins are the anion exchange resin of strong basicity, can be with
Chloride binding is swapped out OH-ion.These types of resin with having certain absorption to Glucosamine, wherein 201 × 7 types
Anion-adsorption acts on most weak, obtained yield highest.After being washed with the aqueous solution containing ethyl alcohol, the Glucosamine meeting of absorption
It is eluted, greatly improves yield.
Preferably, the strong alkali resin is using preceding carry out prewashing, it is preferable that the prewashing is specifically included the highly basic
Property anion exchange resin use salt acid soak 1.5-2.5 hours of 0.8-1.2M, be washed with deionized water to neutrality, then use 0.8-
The soaking with sodium hydroxide of 1.2M 1.5-2.5 hours, then be washed with deionized water to neutral spare.
Preferably, the mass concentration of the aminoglucose hydrochloride aqueous solution be 15%~24%, preferably 20%~
24%.
Preferably, it is repeated 2-4 times using the chloride ion that the anion exchange resin removes, it is preferable that make every time
The quality of anion exchange resin and the quality of aminoglucose hydrochloride are equal.
Preferably, the solvent for washing the anion exchange resin is purified water or ethanol solution, it is preferable that the ethyl alcohol
The volumetric concentration of ethyl alcohol is 2-10% in solution, it is highly preferred that the volumetric concentration of ethyl alcohol is 2-5% in the ethanol solution.
Preferably, the concentration is carried out using nanofiltration membrane, it is preferable that when using nanofiltration membrane concentration, the molecular weight of retention is
100-150D。
Preferably, after the concentration, obtained concentrate, concentration 10-35%, it is preferable that the concentration of the concentrate
For 20-30%.
Preferably, the drying is freeze-drying, it is preferable that the detailed process of the freeze-drying includes, first by sulfuric acid aminoglucose
Sugar juice temperature is down to -20 DEG C~-5 DEG C, is formed after freezing crystalline substance, then be warming up to -10 DEG C~5 DEG C, repeatedly cooling heating 2~5 times, then
- 35 DEG C are cooled to hereinafter, after fully charge, opens vacuum, is gradually warmed up to more than -10 DEG C, after waterline disappears, is continuously heating to
20 DEG C~40 DEG C dryings terminate.
It is lyophilized using method of the invention, the finished product of output is since by freezing repeatedly, quality is close, it is easier to broken
It is broken, there is good physical aspect.
Another aspect of the present invention is related to the Glucosamine Sulphate product arrived prepared using the method, the production
The Glucosamine Sulphate purity of product is higher than 98.0%, catabolite 2 in the product, 5- fructosazine and 2,5- deoxy fructosazine
Content is lower than 0.5%, chloride ion content < 0.1%, sodium ions content < 0.01%, moisture < 1.0%.
Compared with prior art, the invention has the benefit that
1. the present invention improves the yield for preparing Glucosamine Sulphate, yield can be improved by original 50% to 80% with
On.
2. being reduced to 25 hours by original 40 hours present invention reduces the time needed for freeze-drying, reducing energy
Consumption.
3. the present invention improves the purity of Glucosamine Sulphate, reach 98.0% or more, catabolite 2,5- fructosazine and
2,5- deoxy fructosazine contents are lower than 1.0%, chloride ion content < 0.1%, sodium ions content < 0.01%.
4. present invention improves the morphosis of Glucosamine Sulphate, it is easier to which crushing prepares powder, and being suitable for preparation can
The dosage form eaten for human body.
5. being down to < 1.0%, water by original 3.0%~7.0% present invention reduces the moisture of Glucosamine Sulphate
Divide after reducing, product thermal stability is further promoted.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
Embodiment 1
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2.5 hours of 0.8, it is washed with deionized water to neutrality,
Again with soaking with sodium hydroxide 2.5 hours of 0.8, then it is washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 15% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 2 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 2 times, used solvent is purified water.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
10%, sulfuric acid reaction is added.
5. products temperature is first down to -20 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to -10 DEG C, cooling rises repeatedly
Temperature 2 times, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, after of continuing rising
Temperature to 20 DEG C of dryings terminate.
Embodiment 2
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 1.5 hours of 1.2M, it is washed with deionized water to neutrality,
Soaking with sodium hydroxide 1.5 hours for using 1.2M again, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 20% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 3 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 3 times, used solvent is 2% ethanol solution.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
20%, sulfuric acid reaction is added.
5. products temperature is first down to -5 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to 5 DEG C, repeatedly cooling heating 5
It is secondary, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, continues to heat up
Terminate to 40 DEG C of dryings.
Embodiment 3
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2 hours of 1M, it is washed with deionized water to neutrality, then use
The soaking with sodium hydroxide of 1M 2 hours, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 20% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 4 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 4 times, used solvent is the ethanol solution of purified water or 10%.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
25%, sulfuric acid reaction is added.
5. products temperature is first down to -10 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to 0 DEG C, repeatedly cooling heating 4
It is secondary, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, continues to heat up
Terminate to 25 DEG C of dryings.
Embodiment 4
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2 hours of 1M, it is washed with deionized water to neutrality, then use
The soaking with sodium hydroxide of 1M 2 hours, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 24% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 3 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 4 times, used solvent is the ethanol solution of purified water or 10%.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
30%, sulfuric acid reaction is added.
5. products temperature is first down to -20 DEG C~-5 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to -10 DEG C~5 DEG C,
Cooling heating 2~5 times repeatedly, then -35 DEG C are cooled to hereinafter, opening vacuum after fully charge, being gradually heated to -10 DEG C, waterline
After disappearance, being continuously heating to 30 DEG C of dryings terminates.
Embodiment 5
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2 hours of 1M, it is washed with deionized water to neutrality, then use
The soaking with sodium hydroxide of 1M 2 hours, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 24% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 3 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 4 times, used solvent is the ethanol solution of purified water or 10%.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
35%, sulfuric acid reaction is added.
5. products temperature is first down to -20 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to 5 DEG C, repeatedly cooling heating 4
It is secondary, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, continues to heat up
Terminate to 20 DEG C of dryings.
Embodiment 6
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2 hours of 1M, it is washed with deionized water to neutrality, then use
The soaking with sodium hydroxide of 1M 2 hours, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 24% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 3 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 4 times, used solvent is the ethanol solution of purified water or 10%.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
35%, sulfuric acid reaction is added.
5. products temperature is first down to -15 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to -5 DEG C, repeatedly cooling heating
3 times, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, continues to heat up
Terminate to 30 DEG C of dryings.
Embodiment 7
High-purity sulfuric acid Glucosamine is prepared according to the following steps
1. strong-base anion-exchange resin is used salt acid soak 2 hours of 1M, it is washed with deionized water to neutrality, then use
The soaking with sodium hydroxide of 1M 2 hours, then be washed with deionized water to neutral spare.
2. aminoglucose hydrochloride to be configured to 24% aqueous solution, tree is exchanged using pre- washed strong alkalinity anion
Rouge removes the chloride ion in the aqueous solution, is repeated 3 times, every time using with bright strong of Glucosamine Sulphate hydrochloride lamp
Alkalescence anion-exchange resin.
3. washing anion exchange resin 4 times, used solvent is the ethanol solution of purified water or 10%.
4. collecting glucosamine solution, it is concentrated using nanofiltration membrane, molecular cut off 100-150D is concentrated into
35%, sulfuric acid reaction is added.
5. products temperature is first down to -15 DEG C by freeze-drying, formed after freezing crystalline substance, then be warming up to 5 DEG C, repeatedly cooling heating 4
It is secondary, then -35 DEG C are cooled to hereinafter, after fully charge, unlatching vacuum is gradually heated to -10 DEG C, after waterline disappears, continues to heat up
Terminate to 30 DEG C of dryings.
Experimental example 1
Yield, form, moisture, chloride ion content, sodium ions content and thermal stability are examined or check, thermal stability condition is 50 DEG C
Do the total impurities after baking 4 hours.Obtained experimental result such as table 1:
Experimental example 2
Six comparative examples are set, and preparation method step is identical with comparative example, such as 2 institute of table of critical data involved in method
Show,
Table 2
Yield, form, moisture and chloride ion, sodium ions content and thermal stability are examined or check, thermal stability condition is 50 DEG C dry
Total impurities after 4 hours roasting.Obtained experimental result such as table 3,
Table 3
By experimental example 1 as can be seen that preparing Glucosamine Sulphate according to the condition of this law, yield, form, moisture,
Chloride ion content, sodium ions content and thermal stability have good effect.
By experimental example 2 as can be seen that each index change when, to freeze-drying time, yield, form, moisture and chlorine from
Son, sodium ions content and thermal stability, have a great impact.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (6)
1. a kind of preparation method of Glucosamine Sulphate, which is characterized in that the described method includes: by aminoglucose hydrochloride
It is configured to aqueous solution, the chloride ion in the aqueous solution is removed by anion exchange resin, washs the property anion exchange
Resin simultaneously obtains glucosamine solution, and sulfuric acid is added after concentration and reacts to obtain Glucosamine Sulphate solution, dry, obtains
To Glucosamine Sulphate；
The anion exchange resin is strong-base anion-exchange resin, and the strong-base anion-exchange resin is selected from
One of D201, D202, D203, D301,201 × 4 and 201 × 7；
The strong alkali resin is using preceding carry out prewashing, and the prewashing, which specifically includes, makes the strong-base anion-exchange resin
It with salt acid soak 1.5-2.5 hours of 0.8-1.2M, is washed with deionized water to neutrality, then with the soaking with sodium hydroxide of 0.8-1.2M
1.5-2.5 hours, then be washed with deionized water to neutral spare；
The mass concentration of the aminoglucose hydrochloride aqueous solution is 15%~24%；
It is repeated 2-4 times using the chloride ion that the anion exchange resin removes, the anion exchange resin used every time
Quality it is equal with the quality of aminoglucose hydrochloride；
The solvent for washing the anion exchange resin is purified water or ethanol solution, and the volume of ethyl alcohol is dense in the ethanol solution
Degree is 2-10%；
The concentration is carried out using nanofiltration membrane, and when being concentrated using nanofiltration membrane, the molecular weight of retention is 100-150D；
The concentrate obtained after the concentration, concentration 10-35%；
The drying is freeze-drying, and the detailed process of the freeze-drying includes that Glucosamine Sulphate solution temperature is first down to -20 DEG C
It~-5 DEG C, is formed after freezing crystalline substance, then be warming up to -10 DEG C~5 DEG C, repeatedly cooling heating 2~5 times, then is cooled to -35 DEG C hereinafter, complete
After freezing entirely, vacuum is opened, is gradually warmed up to more than -10 DEG C, after waterline disappears, is continuously heating to 20 DEG C~40 DEG C dry knots
Beam.
2. the method according to claim 1, wherein the strong-base anion-exchange resin is selected from 201 × 7.
3. the method according to claim 1, wherein the mass concentration of the aminoglucose hydrochloride aqueous solution
It is 20%~24%.
4. the method according to claim 1, wherein the volumetric concentration of ethyl alcohol is 2-5% in the ethanol solution.
5. the method according to claim 1, wherein the concentration of the concentrate is 20-30%.
6. the Glucosamine Sulphate product being prepared using any one of claim 1-5 the method, feature are existed
In the purity of Glucosamine Sulphate is higher than 98% in the product, catabolite 2,5- fructosazine and 2,5- deoxy fructosazine
Content is below 0.5%, chloride ion content < 0.1%, sodium ions content < 0.01%, moisture < 1.0%.
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