CN105440088B - Glucosamine mixes strontium salt and its preparation method and application - Google Patents
Glucosamine mixes strontium salt and its preparation method and application Download PDFInfo
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- CN105440088B CN105440088B CN201510812858.2A CN201510812858A CN105440088B CN 105440088 B CN105440088 B CN 105440088B CN 201510812858 A CN201510812858 A CN 201510812858A CN 105440088 B CN105440088 B CN 105440088B
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- 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- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen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
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Abstract
The present invention relates to a kind of Glucosamine mixing strontium salts and its preparation method and application.Glucosamine mixing strontium salt has the following structure formula:Glucosamine mixing strontium salt is not hygroscopic, can keep stablizing under normal temperature and humidity, and compared with aminoglucose sugar sulfate, above-mentioned Glucosamine mixing strontium salt more is stablized, and is conducive to the clinical application of Glucosamine.
Description
Technical field
The present invention relates to field of biotechnology more particularly to a kind of Glucosamine mixing strontium salt and preparation method thereof and answer
With.
Background technique
Glucosamine, it is the substance synthesized in human body, is the important nutrient to form cartilage cell, is healthy joint
The natural tissues structural constituent of cartilage.With advancing age, the shortage of the intracorporal Glucosamine of people is increasingly severe, joint
Cartilage is constantly degenerated and is worn.A large amount of medical researches in the U.S., Europe and Japan show: Glucosamine can help to repair and
It safeguards cartilage, and the growth of cartilage cell can be stimulated, thus treatment of arthritis.
However, the hygroscopicity of traditional Glucosamine drug is larger, stability is poor, even in room temperature and normal wet
It is all unstable under degree, cause its clinical application to be restricted.
Summary of the invention
In consideration of it, it is necessary to provide a kind of preferable Glucosamines of stability to mix strontium salt.
In addition, also providing the preparation method and above-mentioned Glucosamine mixing strontium salt of a kind of Glucosamine mixing strontium salt
Application.
A kind of Glucosamine mixing strontium salt, has the following structure formula:
A kind of preparation method of Glucosamine mixing strontium salt, includes the following steps:
Anion exchange resin is impregnated 12~24 hours in distilled water, the anion exchange resin expanded；
The anion exchange resin of the expansion is impregnated 6~10 hours in hydrochloric acid, then makes to be washed with distilled water to
Neutrality then impregnates the anion exchange resin 6~10 hours in the aqueous solution of alkali, then is washed with distilled water to
Property, obtain pretreated anion exchange resin；
The pretreated anion exchange resin is fitted into chromatographic column, the aqueous solution of sulfate is added, is filled
There is the chromatographic column of the anion exchange resin of sulfate radical type；
With the chromatographic column of the excessively described anion exchange resin equipped with sulfate radical type of the aqueous solution of aminoglucose hydrochloride,
And collect eluent；
Under conditions of at 30~45 DEG C and being stirred continuously, strontium chloride is added in the eluent, stirring is obtained to dissolving
Mixed liquor, wherein the molar ratio of the strontium chloride and the aminoglucose hydrochloride is 1:2；
Under conditions of continuing at 30~45 DEG C and be stirred continuously, precipitating reagent is added in the mixed liquor, obtains suspension；
And
By the suspension in 30~35 DEG C insulated and stirred 18~20 hours, be subsequently cooled to 3~5 DEG C, filtered and done
It is dry, obtain the Glucosamine mixing strontium salt for having the following structure formula:
It is described under conditions of 30~45 DEG C with being stirred continuously in one of the embodiments, add in the eluent
In the step of entering the strontium chloride, stirring rate is 100~140 revs/min.
In one of the embodiments, the molar concentration of the aqueous solution of the aminoglucose hydrochloride be 0.3~
0.6mol/L。
It is described in one of the embodiments, to continue under conditions of 30~45 DEG C with being stirred continuously, in the mixed liquor
In the step of middle addition precipitating reagent, the precipitating reagent is acetone or alcohol, the volume of the precipitating reagent and the mixed liquor
Than for 3~6:1.
It is cooled to described in one of the embodiments, cooling using ice-water bath at 3~5 DEG C.
The step of the drying in one of the embodiments, are as follows: 40~50 DEG C drying 18~20 hours.
In one of the embodiments, further include the preparation step of aminoglucose hydrochloride:
Dissolve the chitosan in acetic acid, be then added hydrochloric acid, and in 30~100 DEG C hydrolysis 1~4 hour, then plus
Enter alkali and carry out neutralization reaction, reaction solution is filtered, and filtrate is obtained, and standing 3 hours~5 is small after ethyl alcohol is added in the filtrate
When, it is filtered, obtains the aminoglucose hydrochloride.
The step of ethyl alcohol is added in the filtrate in one of the embodiments, specifically: in the filtrate
The aqueous solution for the ethyl alcohol that mass percentage concentration is 95~98% is added, until the mass percentage of the ethyl alcohol in the filtrate is
70~75%.
Application of the above-mentioned Glucosamine mixing strontium salt in the drug of preparation treatment of arthritis
Strontium in above-mentioned Glucosamine mixing strontium salt can enter cell by calcium channel, in the cell with related calcium
Binding site combines, and has and promotes skeleton development and osteoid formation and the multiple action for adjusting bone metabolism, and Glucosamine
It is main component necessary to human articular cartilage matrix synthesizing amino polysaccharide, the conjunction of glycosaminoglycan and glycoprotein can be promoted
At, chondrocytes for regeneration is stimulated, slows down arthritic pathologic process, relieves pain, improvement function of joint, so that above-mentioned amino Portugal
Grape sugar mixes strontium salt being capable for the treatment of of arthritis；And the hygroscopicity of Glucosamine mixing strontium salt is smaller, it can in room temperature and just
It keeps stablizing under normal humidity, i.e., above-mentioned Glucosamine mixing strontium salt is relatively stable, is conducive to the storage of Glucosamine drug
And application.
Detailed description of the invention
Fig. 1 is the flow chart that the Glucosamine of an embodiment mixes the preparation method of strontium salt；
Fig. 2 is Glucosamine mixing prepared by the aminoglucose hydrochloride, strontium chloride, embodiment 1 of the preparation of embodiment 1
The XRD spectrum of the mixture of aminoglucose hydrochloride and strontium chloride prepared by strontium salt and embodiment 1, the expression of curve 1 are
The XRD curve of Glucosamine mixing strontium salt prepared by embodiment 1, what curve 2 indicated is Glucosamine prepared by embodiment 1
The XRD curve of hydrochloride, curve 3 indicate that the XRD of the mixture of aminoglucose hydrochloride prepared by embodiment 1 and strontium chloride is bent
Line, curve 4 indicate the XRD curve of strontium chloride.
Specific embodiment
Glucosamine mixing strontium salt and its preparation method and application is made mainly in combination with drawings and the specific embodiments below
Further details of explanation.
The Glucosamine of one embodiment mixes strontium salt, has the following structure formula:
Glucosamine mixing strontium salt can be applied in the drug of preparation treatment of arthritis.
Strontium in above-mentioned Glucosamine mixing strontium salt can enter cell by calcium channel, in the cell with related calcium
Binding site combines, and has and promotes skeleton development and osteoid formation and the multiple action for adjusting bone metabolism, and Glucosamine
It is main component necessary to human articular cartilage matrix synthesizing amino polysaccharide, the conjunction of glycosaminoglycan and glycoprotein can be promoted
At, chondrocytes for regeneration is stimulated, slows down arthritic pathologic process, relieves pain, improvement function of joint, so that above-mentioned amino Portugal
Grape sugar mixes strontium salt being capable for the treatment of of arthritis；And the hygroscopicity of Glucosamine mixing strontium salt is smaller, it can in room temperature and just
It keeps stablizing under normal humidity, i.e., above-mentioned Glucosamine mixing strontium salt is relatively stable, is conducive to the storage of Glucosamine drug
And application.
As shown in Figure 1, the preparation method of the Glucosamine mixing strontium salt of an embodiment, can be used for preparing above-mentioned amino
Glucose mixes strontium salt, which includes the following steps:
Step S110: anion exchange resin is impregnated 12~24 hours in distilled water, and the anion expanded is handed over
Change resin.
Specifically, the volume ratio of anion exchange resin and distilled water is 1:3~6.By by anion exchange resin in
It is impregnated 12~24 hours in distilled water, expands anion exchange resin sufficiently, obtaining particle is more anion exchange
Resin.
Step S120: the anion exchange resin of expansion is impregnated 6~10 hours in hydrochloric acid, then using distillation washing
It washs to neutrality, then impregnates anion exchange resin 6~10 hours in the aqueous solution of alkali, then be washed with distilled water to
Property, obtain pretreated anion exchange resin.
Wherein, in step S120, the volume ratio of the anion exchange resin of expansion and hydrochloric acid is 1:2~6, and the matter of hydrochloric acid
Measuring percentage concentration is 4~10%.
Wherein, in step S120, the volume ratio of the aqueous solution of anion exchange resin and alkali is 1:2~6, the aqueous solution of alkali
The sodium hydrate aqueous solution for being 4~10% for mass percentage concentration.
Step S130: pretreated anion exchange resin is fitted into chromatographic column, is added the aqueous solution of sulfate, is obtained
To the chromatographic column of the anion exchange resin equipped with sulfate radical type.
Wherein, the aqueous solution of sulfate can be aqueous solution, the aqueous solution of potassium sulfate etc. of sodium sulphate, preferably sodium sulphate
Aqueous solution.
Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is 1~5mol/L.
Step S140: the layer of the anion exchange resin equipped with sulfate radical type is crossed with the aqueous solution of aminoglucose hydrochloride
Column is analysed, and collects eluent.
Wherein, contain aminoglucose sulfate in eluent obtained in step S140.
Wherein, the molar concentration of the Ammonia In Aqueous Solution base glucosamine salt hydrochlorate of aminoglucose hydrochloride be 0.3~
0.6mol/L。
Wherein, aminoglucose hydrochloride can be bought by market and be obtained.In the present embodiment, glucosamine hydrochloric acid
Salt is prepared by following preparation step: being dissolved the chitosan in acetic acid, hydrochloric acid is then added, and in 30~100 DEG C of water
Solution reaction 1~4 hour adds alkali and carries out neutralization reaction, and reaction solution is filtered, and filtrate is obtained, after ethyl alcohol is added in filtrate
3~5 hours are stood, is filtered, obtains aminoglucose hydrochloride.
Wherein, in the step of preparing aminoglucose hydrochloride, in filtrate the step of addition ethyl alcohol specifically: filtering
The aqueous solution for the ethyl alcohol that mass percentage concentration is 95~98% is added in liquid, until the mass percentage of the ethyl alcohol in filtrate is
70~75%.
Wherein, it dissolves the chitosan in the step in acetic acid, the mass percentage concentration of acetic acid is 1%~3%.Wherein,
The mass ratio of chitosan and acetic acid is 3:7~3:10.
Wherein, in the step of dissolving the chitosan in acetic acid, hydrochloric acid is then added, the quality percentage of the hydrochloric acid of addition is dense
Degree is 5%~15%.Wherein, the mass ratio of the hydrogen chloride in salt water and chitosan is 5:3~7:3.
Wherein, in the step of preparing aminoglucose hydrochloride, the alkali that neutralization reaction is added is that mass percentage is
The aqueous solution of 10~15% sodium hydroxide.It is appreciated that the alkali being added at this time can also be commonly used in the art alkali aqueous solution,
Such as aqueous solution of potassium hydroxide etc..
Wherein, in the step of preparing aminoglucose hydrochloride, the method for suction filtration is vacuum filtration.
It wherein, further include that will filter to obtain after the step of filtering in the step of preparing aminoglucose hydrochloride
Solid in 40~60 DEG C be dried in vacuo 3~5 hours the step of.
Step S150: under conditions of at 30~45 DEG C and being stirred continuously, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor.
Wherein, the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
Wherein, in step S150, under conditions of at 30~45 DEG C and being stirred continuously, the step of strontium chloride is added in eluent
In rapid, stirring rate is 100~140 revs/min.
Step S160: under conditions of continuing at 30~45 DEG C and be stirred continuously, precipitating reagent is added in mixed liquor, is hanged
Supernatant liquid.
Wherein, the stirring rate of step S160 is 100~140 revs/min.
Wherein, it in the step of continuing under conditions of 30~45 DEG C with being stirred continuously, precipitating reagent is added in mixed liquor, sinks
Shallow lake agent is acetone or alcohol, and the volume ratio of precipitating reagent and mixed liquor is 3~6:1.
Step S170: by suspension in 30~35 DEG C insulated and stirred 18~20 hours, 3~5 DEG C are subsequently cooled to, through filtering
And drying, obtain the Glucosamine mixing strontium salt for having the following structure formula:
Wherein, it is cooled to cooling using ice-water bath at 3~5 DEG C.
Wherein, dry step are as follows: 40~50 DEG C drying 18~20 hours.
Above-mentioned preparation method is simple, and yield is higher, and the purity of the Glucosamine mixing strontium salt prepared is higher.
The following are specific embodiment parts:
Embodiment 1
The preparation step of the Glucosamine mixing strontium salt of the present embodiment is as follows:
(1) anion exchange resin is impregnated 12 hours in distilled water, the anion exchange resin expanded,
In, the volume ratio of anion exchange resin and distilled water is 1:4.
(2) volume ratio for the hydrochloric acid for being 7% according to the anion exchange resin of expansion and mass percentage concentration is 1:4, will
The anion exchange resin of expansion impregnates 8 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality；Then according to anion
The volume ratio for the sodium hydrate aqueous solution that exchanger resin and mass percentage concentration are 8% is 1:4, by anion exchange resin in hydrogen
It is impregnated 8 hours in aqueous solution of sodium oxide, then is washed with distilled water to neutrality, obtain pretreated anion exchange resin.
(3) pretreated anion exchange resin is fitted into chromatographic column, adds the aqueous solution of sodium sulphate, is equipped with
The chromatographic column of the anion exchange resin of sulfate radical type.Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is
3mol/L。
(4) it dissolves the chitosan in the acetic acid that mass percentage concentration is 2%, obtains chitosan solution, matter is then added
Measure the hydrochloric acid that percentage concentration is 10%, wherein the mass ratio of chitosan and acetic acid is 3:10, hydrogen chloride and chitosan in salt water
Mass ratio be 5:3；Then at 70 DEG C hydrolysis 2.5 hours, then in the reaction solution after hydrolysis be added quality percentage
The aqueous solution for the sodium hydroxide that concentration is 12% carries out neutralization reaction, and the reaction solution filtering removal filter residue after neutralization reaction obtains
To filtrate, the aqueous solution for the ethyl alcohol that mass percentage concentration is 97% is added in filtrate, until the quality hundred of the ethyl alcohol in filtrate
Dividing content is 73%, stands 5 hours after shaking up, and white precipitate is precipitated, is filtered, and obtained solid is small in 50 DEG C of vacuum drying 4
When, obtain aminoglucose hydrochloride.
(5) aqueous solution for the aminoglucose hydrochloride for being 0.5mol/L with molar concentration cross equipped with sulfate radical type yin from
The chromatographic column of sub-exchange resin, and collect eluent.
(6) under conditions of being stirred continuously for 40 DEG C and 120 revs/min, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor, wherein the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
(7) continue under conditions of being stirred continuously for 40 DEG C and 120 revs/min, acetone is added in mixed liquor, is suspended
Liquid, wherein the volume ratio of acetone and mixed liquor is 4:1.
(8) insulated and stirred 19 hours after suspension being cooled to 30 DEG C, are then cooled to 4 DEG C in ice-water bath, through filtering,
It is 19 hours dry in 45 DEG C that obtained solid will be filtered, obtain Glucosamine mixing strontium salt, yield 85%, purity is
90%.
The hygroscopicity of the Glucosamine mixing strontium salt of test the present embodiment: 0.1 gram of sheet is first weighed using electronic balance
The Glucosamine of embodiment mixes strontium salt, then places at room temperature, respectively to the amino Portugal after placing 4 hours and 12 hours
Grape sugar mixes strontium salt weighing, wherein after the Glucosamine mixing strontium salt of the present embodiment places 4 hours and 12 hours at room temperature
Quality and percent mass penalty be shown in Table 1.
Embodiment 2
The preparation step of the Glucosamine mixing strontium salt of the present embodiment is as follows:
(1) anion exchange resin is impregnated 18 hours in distilled water, the anion exchange resin expanded,
In, the volume ratio of anion exchange resin and distilled water is 1:3.
(2) volume ratio for the hydrochloric acid for being 4% according to the anion exchange resin of expansion and mass percentage concentration is 1:6, will
The anion exchange resin of expansion impregnates 6 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality；Then according to anion
The volume ratio for the sodium hydrate aqueous solution that exchanger resin and mass percentage concentration are 4% is 1:6, by anion exchange resin in hydrogen
It is impregnated 10 hours in aqueous solution of sodium oxide, then is washed with distilled water to neutrality, obtain pretreated anion exchange resin.
(3) pretreated anion exchange resin is fitted into chromatographic column, adds the aqueous solution of sodium sulphate, is equipped with
The chromatographic column of the anion exchange resin of sulfate radical type.Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is
5mol/L。
(4) it dissolves the chitosan in the acetic acid that mass percentage concentration is 2%, obtains chitosan solution, matter is then added
Measure the hydrochloric acid that percentage concentration is 10%, wherein the mass ratio of chitosan and acetic acid is 3:7, hydrogen chloride and chitosan in salt water
Mass ratio be 7:3；Then at 30 DEG C hydrolysis 4 hours, then in the reaction solution after hydrolysis be added quality percentage it is dense
The aqueous solution for the sodium hydroxide that degree is 10% carries out neutralization reaction, and the reaction solution filtering removal filter residue after neutralization reaction obtains
The aqueous solution for the ethyl alcohol that mass percentage concentration is 98% is added in filtrate in filtrate, until the quality percentage of the ethyl alcohol in filtrate
Content is 70%, stands 3 hours after shaking up, and white precipitate is precipitated, is filtered, and obtained solid is dried in vacuo 5 hours at 40 DEG C,
Obtain aminoglucose hydrochloride.
(5) aqueous solution for the aminoglucose hydrochloride for being 0.3mol/L with molar concentration cross equipped with sulfate radical type yin from
The chromatographic column of sub-exchange resin, and collect eluent.
(6) under conditions of being stirred continuously for 45 DEG C and 100 revs/min, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor, wherein the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
(7) continue under conditions of being stirred continuously for 45 DEG C and 100 revs/min, ethyl alcohol is added in mixed liquor, is suspended
Liquid, wherein the volume ratio of ethyl alcohol and mixed liquor is 3:1.
(8) insulated and stirred 18 hours after suspension being cooled to 35 DEG C, are then cooled to 3 DEG C in ice-water bath, through filtering,
It is 20 hours dry in 40 DEG C that obtained solid will be filtered, obtain Glucosamine mixing strontium salt, yield 85%, purity is
90%.
And the Glucosamine mixing strontium salt of the present embodiment has the map similar with Fig. 2 of embodiment 1.
The hygroscopicity that the Glucosamine mixing strontium salt of the present embodiment is tested using the identical test method of embodiment 1, is obtained
Glucosamine to the present embodiment mixes the quality after strontium salt is placed 4 hours and 12 hours at room temperature and percent mass penalty is shown in
Table 1.
Embodiment 3
The preparation step of the Glucosamine mixing strontium salt of the present embodiment is as follows:
(1) anion exchange resin is impregnated 24 hours in distilled water, the anion exchange resin expanded,
In, the volume ratio of anion exchange resin and distilled water is 1:6.
(2) volume ratio for the hydrochloric acid for being 10% according to the anion exchange resin of expansion and mass percentage concentration is 1:2, will
The anion exchange resin of expansion impregnates 10 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality；Then according to yin from
The volume ratio for the sodium hydrate aqueous solution that sub-exchange resin and mass percentage concentration are 10% is 1:2, by anion exchange resin
It is impregnated 6 hours in sodium hydrate aqueous solution, then is washed with distilled water to neutrality, obtain pretreated anion exchange resin.
(3) pretreated anion exchange resin is fitted into chromatographic column, adds the aqueous solution of sodium sulphate, is equipped with
The chromatographic column of the anion exchange resin of sulfate radical type.Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is
1mol/L。
(4) it dissolves the chitosan in the acetic acid that mass percentage concentration is 2%, obtains chitosan solution, matter is then added
Measure the hydrochloric acid that percentage concentration is 10%, wherein the mass ratio of chitosan and acetic acid is 3:9, hydrogen chloride and chitosan in salt water
Mass ratio be 6:3；Then at 100 DEG C hydrolysis 1 hour, then in the reaction solution after hydrolysis be added quality percentage it is dense
The aqueous solution for the sodium hydroxide that degree is 15% carries out neutralization reaction, and the reaction solution filtering removal filter residue after neutralization reaction obtains
The aqueous solution for the ethyl alcohol that mass percentage concentration is 95% is added in filtrate in filtrate, until the quality percentage of the ethyl alcohol in filtrate
Content is 75%, stands 4 hours after shaking up, and white precipitate is precipitated, is filtered, and obtained solid is dried in vacuo 3 hours at 60 DEG C,
Obtain aminoglucose hydrochloride.
(5) aqueous solution for the aminoglucose hydrochloride for being 0.6mol/L with molar concentration cross equipped with sulfate radical type yin from
The chromatographic column of sub-exchange resin, and collect eluent.
(6) under conditions of being stirred continuously for 30 DEG C and 140 revs/min, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor, wherein the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
(7) continue under conditions of being stirred continuously for 30 DEG C and 140 revs/min, acetone is added in mixed liquor, is suspended
Liquid, wherein the volume ratio of acetone and mixed liquor is 6:1.
(8) insulated and stirred 20 hours after suspension being cooled to 30 DEG C, are then cooled to 5 DEG C in ice-water bath, through filtering,
It is 18 hours dry in 50 DEG C that obtained solid will be filtered, obtain Glucosamine mixing strontium salt, yield 85%, purity is
90%.
The hygroscopicity that the Glucosamine mixing strontium salt of the present embodiment is tested using the identical test method of embodiment 1, is obtained
Glucosamine to the present embodiment mixes the quality after strontium salt is placed 4 hours and 12 hours at room temperature and percent mass penalty is shown in
Table 1.
Embodiment 4
The preparation step of the Glucosamine mixing strontium salt of the present embodiment is as follows:
(1) anion exchange resin is impregnated 16 hours in distilled water, the anion exchange resin expanded,
In, the volume ratio of anion exchange resin and distilled water is 1:5.
(2) volume ratio for the hydrochloric acid for being 5% according to the anion exchange resin of expansion and mass percentage concentration is 1:3, will
The anion exchange resin of expansion impregnates 9 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality；Then according to anion
The volume ratio for the sodium hydrate aqueous solution that exchanger resin and mass percentage concentration are 5% is 1:3, by anion exchange resin in hydrogen
It is impregnated 9 hours in aqueous solution of sodium oxide, then is washed with distilled water to neutrality, obtain pretreated anion exchange resin.
(3) pretreated anion exchange resin is fitted into chromatographic column, adds the aqueous solution of sodium sulphate, is equipped with
The chromatographic column of the anion exchange resin of sulfate radical type.Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is
2mol/L。
(4) it dissolves the chitosan in the acetic acid that mass percentage concentration is 1%, obtains chitosan solution, matter is then added
Measure the hydrochloric acid that percentage concentration is 5%, wherein the mass ratio of chitosan and acetic acid is 3:8, the hydrogen chloride and chitosan in salt water
Mass ratio is 6:3；Then at 80 DEG C hydrolysis 2 hours, mass percentage concentration then is added in the reaction solution after hydrolysis
For the aqueous solution of 13% sodium hydroxide, neutralization reaction is carried out, the reaction solution filtering removal filter residue after neutralization reaction is filtered
The aqueous solution for the ethyl alcohol that mass percentage concentration is 96% is added in liquid in filtrate, until the quality percentage of the ethyl alcohol in filtrate contains
Amount is 72%, stands 4 hours after shaking up, and white precipitate is precipitated, is filtered, and obtained solid is dried in vacuo 4 hours at 60 DEG C, is obtained
To aminoglucose hydrochloride.
(5) aqueous solution for the aminoglucose hydrochloride for being 0.4mol/L with molar concentration cross equipped with sulfate radical type yin from
The chromatographic column of sub-exchange resin, and collect eluent.
(6) under conditions of being stirred continuously for 35 DEG C and 110 revs/min, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor, wherein the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
(7) continue under conditions of being stirred continuously for 30 DEG C and 140 revs/min, acetone is added in mixed liquor, is suspended
Liquid, wherein the volume ratio of acetone and mixed liquor is 5:1.
(8) insulated and stirred 19 hours after suspension being cooled to 32 DEG C, are then cooled to 4 DEG C in ice-water bath, through filtering,
It is 18 hours dry in 50 DEG C that obtained solid will be filtered, obtain Glucosamine mixing strontium salt, yield 85%, purity is
90%.
The hygroscopicity that the Glucosamine mixing strontium salt of the present embodiment is tested using the identical test method of embodiment 1, is obtained
Glucosamine to the present embodiment mixes the quality after strontium salt is placed 4 hours and 12 hours at room temperature and percent mass penalty is shown in
Table 1.
Embodiment 5
The preparation step of the Glucosamine mixing strontium salt of the present embodiment is as follows:
(1) anion exchange resin is impregnated 20 hours in distilled water, the anion exchange resin expanded,
In, the volume ratio of anion exchange resin and distilled water is 1:4.
(2) volume ratio for the hydrochloric acid for being 8% according to the anion exchange resin of expansion and mass percentage concentration is 1:5, will
The anion exchange resin of expansion impregnates 8 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality；Then according to anion
The volume ratio for the sodium hydrate aqueous solution that exchanger resin and mass percentage concentration are 8% is 1:5, by anion exchange resin in hydrogen
It is impregnated 8 hours in aqueous solution of sodium oxide, then is washed with distilled water to neutrality, obtain pretreated anion exchange resin.
(3) pretreated anion exchange resin is fitted into chromatographic column, adds the aqueous solution of sodium sulphate, is equipped with
The chromatographic column of the anion exchange resin of sulfate radical type.Wherein, the molar concentration of the sulfate radical in the aqueous solution of sulfate is
4mol/L。
(4) it dissolves the chitosan in the acetic acid that mass percentage concentration is 3%, obtains chitosan solution, matter is then added
Measure the hydrochloric acid that percentage concentration is 15%, wherein the mass ratio of chitosan and acetic acid is 3:8, hydrogen chloride and chitosan in salt water
Mass ratio be 6:3；Then at 70 DEG C hydrolysis 2.5 hours, then in the reaction solution after hydrolysis be added quality percentage
The aqueous solution for the sodium hydroxide that concentration is 14% carries out neutralization reaction, and the reaction solution filtering removal filter residue after neutralization reaction obtains
To filtrate, the aqueous solution for the ethyl alcohol that mass percentage concentration is 96% is added in filtrate, until the quality hundred of the ethyl alcohol in filtrate
Dividing content is 74%, stands 4 hours after shaking up, and white precipitate is precipitated, is filtered, and obtained solid is small in 50 DEG C of vacuum drying 4
When, obtain aminoglucose hydrochloride.
(5) aqueous solution for the aminoglucose hydrochloride for being 0.5mol/L with molar concentration cross equipped with sulfate radical type yin from
The chromatographic column of sub-exchange resin, and collect eluent.
(6) under conditions of being stirred continuously for 30 DEG C and 140 revs/min, strontium chloride is added in eluent, stirs to molten
Solution, obtains mixed liquor, wherein the molar ratio of strontium chloride and aminoglucose hydrochloride is 1:2.
(7) continue under conditions of being stirred continuously for 30 DEG C and 140 revs/min, acetone is added in mixed liquor, is suspended
Liquid, wherein the volume ratio of acetone and mixed liquor is 6:1.
(8) insulated and stirred 18 hours after suspension being cooled to 30 DEG C, are then cooled to 5 DEG C in ice-water bath, through filtering,
It is 18 hours dry in 50 DEG C that obtained solid will be filtered, obtain Glucosamine mixing strontium salt, yield 85%, purity is
90%.
The hygroscopicity that the Glucosamine mixing strontium salt of the present embodiment is tested using the identical test method of embodiment 1, is obtained
Glucosamine to the present embodiment mixes the quality after strontium salt is placed 4 hours and 12 hours at room temperature and percent mass penalty is shown in
Table 1.
Comparative example 1
Comparative example 1 is existing aminoglucose sulfate.Using the identical test method test comparison example 1 of embodiment 1
Aminoglucose sulfate hygroscopicity, obtain the initial mass of the aminoglucose sulfate of comparative example 1, put at room temperature
Quality and percent mass penalty after setting 4 hours and 12 hours are shown in Table 1.
The aminoglucose sulfate of the Glucosamine mixing strontium salt and comparative example 1 for the Examples 1 to 5 that table 1 indicates
Initial mass, and the quality after placement 4 hours and 12 hours and percent mass penalty are shown in Table 1 at room temperature.
Table 1
The 4 hours percent mass penalties of the Glucosamine mixing strontium salt of Examples 1 to 5 placed at room temperature are at most only
Quality hardly changes after 0.4%, and 4 hours, and the aminoglucose sulfate of comparative example 1 is placed 4 hours at room temperature
Percent mass penalty afterwards is up to 4.6%, and percent mass penalty is up to 19.1% after 12 hours, it is clear that the amino Portugal of Examples 1 to 3
Grape sugar, which mixes strontium salt, has the hygroscopicity smaller than the aminoglucose sulfate of comparative example 1, can be more steady under normal humidity
It is fixed.
Fig. 2 is Glucosamine mixing prepared by the aminoglucose hydrochloride, strontium chloride, embodiment 1 of the preparation of embodiment 1
The XRD spectrum of the mixture of aminoglucose hydrochloride and strontium chloride prepared by strontium salt and embodiment 1, the expression of curve 1 are
The XRD curve of Glucosamine mixing strontium salt prepared by embodiment 1, what curve 2 indicated is Glucosamine prepared by embodiment 1
The XRD curve of hydrochloride, curve 3 indicate that the XRD of the mixture of aminoglucose hydrochloride prepared by embodiment 1 and strontium chloride is bent
Line, curve 4 indicate the XRD curve of strontium chloride.From figure 2 it can be seen that Glucosamine mixing strontium salt prepared by embodiment 1
The XRD curve of the mixture of XRD curve and aminoglucose hydrochloride and strontium chloride is different, and ammonia prepared by embodiment 1
The XRD curve and the XRD curve of the XRD curve of aminoglucose hydrochloride, strontium chloride of base glucose mixing strontium salt are different, show
So, illustrate that Glucosamine mixing strontium salt prepared by embodiment 1 is not that aminoglucose hydrochloride and strontium chloride are simply mixed
It closes, but has obtained a kind of new substance.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (8)
1. a kind of preparation method of Glucosamine mixing strontium salt, which comprises the steps of:
Anion exchange resin is impregnated 12~24 hours in distilled water, the anion exchange resin expanded；
The anion exchange resin of the expansion is impregnated 6~10 hours in hydrochloric acid, then makes to be washed with distilled water to neutrality,
Then the anion exchange resin is impregnated 6~10 hours in the aqueous solution of alkali, then is washed with distilled water to neutrality, obtained
Pretreated anion exchange resin；
The pretreated anion exchange resin is fitted into chromatographic column, the aqueous solution of sulfate is added, is obtained equipped with sulphur
The chromatographic column of the anion exchange resin of acid group type, wherein the molar concentration of the sulfate radical in the aqueous solution of sulfate be 1~
5mol/L；
With the chromatographic column of the excessively described anion exchange resin equipped with sulfate radical type of the aqueous solution of aminoglucose hydrochloride, and receive
Collect eluent；
Under conditions of at 30~45 DEG C and being stirred continuously, strontium chloride is added in the eluent, stirring is mixed to dissolving
Liquid, wherein the molar ratio of the strontium chloride and the aminoglucose hydrochloride is 1:2；
Under conditions of continuing at 30~45 DEG C and be stirred continuously, precipitating reagent is added in the mixed liquor, obtains suspension；And
By the suspension in 30~35 DEG C insulated and stirred 18~20 hours, be subsequently cooled to 3~5 DEG C, filtered and dried, obtained
Glucosamine to the formula that has the following structure mixes strontium salt:
2. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that described 30~45
DEG C and under conditions of being stirred continuously, in the step of strontium chloride is added in the eluent, stirring rate is 100~140
Rev/min.
3. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that the aminoglucose
The molar concentration of the aqueous solution of sugared hydrochloride is 0.3~0.6mol/L.
4. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that the continuation is 30
~45 DEG C and under conditions of being stirred continuously, in the step of precipitating reagent is added in the mixed liquor, the precipitating reagent is third
The volume ratio of ketone or ethyl alcohol, the precipitating reagent and the mixed liquor is 3~6:1.
5. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that described to be cooled to 3
It is cooling using ice-water bath at~5 DEG C.
6. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that the step of the drying
Suddenly are as follows: 40~50 DEG C drying 18~20 hours.
7. the preparation method of Glucosamine mixing strontium salt according to claim 1, which is characterized in that further include amino Portugal
The preparation step of grape sugar hydrochloride:
Dissolve the chitosan in acetic acid, be then added hydrochloric acid, and in 30~100 DEG C hydrolysis 1~4 hour, add alkali
Neutralization reaction is carried out, reaction solution is filtered, and filtrate is obtained, and stands 3 hours~5 hours after ethyl alcohol is added in the filtrate, is passed through
It filters, obtains the aminoglucose hydrochloride.
8. the preparation method of Glucosamine mixing strontium salt according to claim 7, which is characterized in that in the filtrate
The step of ethyl alcohol is added specifically: the water-soluble of the ethyl alcohol that mass percentage concentration is 95~98% is added in the filtrate
Liquid, until the mass percentage of the ethyl alcohol in the filtrate is 70~75%.
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