CN103601763A - Method for preparing glucosamine potassium sulfate compound salt - Google Patents
Method for preparing glucosamine potassium sulfate compound salt Download PDFInfo
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- CN103601763A CN103601763A CN201310620455.9A CN201310620455A CN103601763A CN 103601763 A CN103601763 A CN 103601763A CN 201310620455 A CN201310620455 A CN 201310620455A CN 103601763 A CN103601763 A CN 103601763A
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- double salt
- sulfate potassium
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Abstract
The invention relates to a method for preparing a glucosamine potassium sulfate compound salt. The method comprises the following steps: (1) preparing a mixed solution of water and tetrahydrofuran which are in the volume ratio of 1: (10-15); (2) heating to the temperature of 30-60 DEG C, adding potassium bisulfate and glucosamine hydrochloride which are in the mole ratio of 1.0: (2.0-2.2) into the mixed solution, and stirring for 10-20 hours; (3) cooling to the temperature of 0-5 DEG C, crystallizing for 3-6 hours, filtrating to obtain crystals, and carrying out vacuum drying for 0.5-5 hours at the temperature of 40-60 DEG C, thereby obtaining the glucosamine potassium sulfate compound salt. According to the method, the operation is simpler and controllable, the realization is easy, the yield is high, and products with consistent crystal forms and better uniformity are easily produced and obtained and can meet the requirements of pharmaceutical grade products; the method further has the advantages of convenience in solvent recovery, simplicity in aftertreatment, little pollution, easiness in repetition, suitability for industrial production, and the like.
Description
Technical field
The invention belongs to oceanic resources and pharmaceutical chemistry technical field, specifically relate to a kind of preparation method of Glucosamine Sulfate Potassium double salt.
Background technology
Glucosamine sulphate is releasing arthritis and rheumatisant's pain obviously, improve, prevent, treat and reparation connective tissue damage, with bone and sacroiliitis, also there is certain curative effect, also contribute to healing acute, chronic inflammatory diseases, therefore heart trouble, pneumonia are also had to certain curative effect simultaneously.But glucosamine sulphate is extremely unstable, has water absorbability, easily oxidized, so that glucosamine sulphate is difficult to be applied clinically.
Glucosamine Sulfate Potassium double salt is a kind of marine biological preparation, not only has the efficacy of drugs identical with glucosamine sulphate, pharmaceutically, can also treat the clinical function such as a mouthful interior inflammation, suppurative eczema, venomous snake bite; On daily necessities, as beauty cream, shampoo additive etc. in makeup, can optimize skin, play anti-oxidation efficacy; In agricultural, can be used for plant growth regulating, plant promoting agent etc.The physiological action also with anti-ageing, fat-reducing, endocrine regulation multiple beneficial meanwhile; Be widely used in foodstuff additive and protective foods production this, the more important thing is that it is more stable under normal temperature and normal humidity, make it in clinical use, become possibility.
In prior art, the preparation of Glucosamine Sulfate Potassium double salt adopts mechanical-physical to mix mostly, as pharmaceutical grade product, there is more defect in the Glucosamine Sulfate Potassium double salt that the method prepares, product is extremely unstable, there is water absorbability, optical purity is extremely unstable in 24 hours, and nitrogen test shows that mixing logical nitrogen post chlorization thing content changes; The product of physical mixed, because the density between material is different, adds the reasons such as operation simultaneously, and product content uniformity coefficient is poor.
Chinese patent CN102850411A discloses a kind of preparation method of D-glucosamine sulfuric acid potassium chloride salt, the method is by using D-Glucosamine Hydrochloride the alkaline matter that contains potassium, make it to become the D-glucosamine aqueous solution of free state, then add sulfuric acid make it salify and simultaneously in solution with Repone K complexing, obtain the solution that contains D-glucosamine potassium sulfate salt complex, through processing, vacuum-drying, obtains white D-glucosamine sulfuric acid potassium chloride salt complex compound.Above-mentioned preparation method's process is loaded down with trivial details, and productive rate is low, and the alkaline matter wherein relating to reclaims trouble, is not suitable for suitability for industrialized production.
Chinese patent CN101066274A discloses the preparation method of the compound salt of a kind of D-glucosamine potassium sulfate, belongs to oceanic resources and pharmaceutical chemistry technical field.It is extremely unstable that it has solved the glucosamine sulphate of prior art, has water absorbability, easily oxidized defect; And different, the poor defect of degree of uniformity of density between the compound salt material of the Glucosamine Sulfate Potassium of existing employing physical mixed.But, this inventive method is difficult to carry out repetition, because Glucosamine Sulfate Potassium, potassium sulfate and Glucosamine Sulfate Potassium double salt are all insoluble to organic solvent, can be water-soluble, but different solubility under differing temps, after general reactant is water-soluble by first control condition, add again organic solvent to react under certain condition, in reaction process, condition is controlled harsh, after reaction finishes, for the Tc of aftertreatment, also needs very high requirement, be difficult to obtain all qualified products of indices, products collection efficiency is low.
Summary of the invention
The deficiency existing in order to overcome prior art, the invention provides a kind of easy and simple to handle, productive rate is high, the preparation method of the Glucosamine Sulfate Potassium double salt of good evenness.
A preparation method for Glucosamine Sulfate Potassium double salt, comprises the steps:
(1) dose volume is than being the water of 1:10～15, tetrahydrofuran (THF) mixing solutions;
(2) be warming up to 30～60 ℃, the sal enixum that is 1.0:2.0～2.2 by mol ratio, glucosamine hydrochloride add in mixing solutions, stir 10～20h;
(3) be cooled to 0～5 ℃, crystallization 3～6h, filters to obtain crystallisate; At 40～60 ℃, vacuum-drying 0.5～5.0h obtains Glucosamine Sulfate Potassium double salt.
Preferably, in step (1), the volume ratio 1:12 of water, tetrahydrofuran (THF).
Preferably, in step (2), the mol ratio of sal enixum, glucosamine hydrochloride is 1.0:2.0, and controlling mixing speed is 100～180 revs/min.This mixing speed is not only conducive to promote the carrying out of reaction, and can not damage crystal formation.
Preferably, in step (3), adopt ice-water bath to lower the temperature, Tc is 2 ℃, and vacuum-drying temperature is 50 ℃.
Preferably, described water is pure water.In pure water, impurity is few, is conducive to prepare that productive rate is high, the Glucosamine Sulfate Potassium double salt of quality better.
Preferably, the preparation method of Glucosamine Sulfate Potassium double salt comprises the steps:
(1) dose volume is than being the water of 1:12, tetrahydrofuran (THF) mixing solutions;
(2) be warming up to 55 ℃, the sal enixum that is 1.0:2.0 by mol ratio, glucosamine hydrochloride add in mixing solutions, stir 15h; Wherein, controlling mixing speed is 170 revs/min;
(3) be cooled to 2 ℃, crystallization 4h, filters to obtain crystallisate; At 50 ℃, vacuum-drying 3h obtains Glucosamine Sulfate Potassium double salt.
Adopt single step reaction, make sal enixum, glucosamine hydrochloride at a certain temperature, organic solvent tetrahydrofuran also carries out the reaction of dissolving limit, limit in the mixing solutions of water existence, operate more simply controlled, generation is positively charged ion by protonated glucosamine and potassium ion, and hydrogen sulfate ion and the chlorion compound salt that is negatively charged ion, this compound salt is the compound salt of ligand.The present invention adopts organic solvent-aqueous systems, by single step reaction, prepare Glucosamine Sulfate Potassium double salt, under certain speed conditions, take tetrahydrofuran (THF) as solvent main body, and under certain water yield exists, promote the carrying out of reaction, tetrahydrofuran (THF) at a certain temperature, salt is also had to certain solvability, and when low temperature, after reaction finishes, owing to only there being the water of relatively small amount in system, avoided in crystallisation process, water dissolves product and causes product not separate out completely, affects productive rate.
In reaction process of the present invention, the control of temperature of reaction is very crucial, and excess Temperature not only can affect reaction process, and product is prone to browning phenomenon, affects product quality; Temperature is too low, is unfavorable for reacting carrying out, and reacts too slow, not only uneconomical, and the quality of the finished product is also had to certain influence.
The present invention's operation is more simply controlled, is easy to realize, and productive rate is high, easily produces and obtains the better product of crystal formation consistent and uniform degree, can meet the requirement of pharmaceutical grade product; The present invention also have convenient solvent reclaiming, aftertreatment simple, pollute less, the advantage such as easily repetition, suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described, but protection scope of the present invention is not limited to this.
Embodiment 1
40ml pure water and 480ml tetrahydrofuran (THF), after being uniformly mixed, be added in four-hole boiling flask, be warming up to 55 ℃, add 10.9g(0.08mol) sal enixum, 34.5g(0.16mol) glucosamine hydrochloride, stirring reaction 15h, controlling mixing speed is 170 revs/min; Then with ice-water bath, cool the temperature to 2 ℃ of insulation crystallization 4h, filter to obtain crystallisate; Crystallisate vacuum-drying 3h at 50 ℃ obtains Glucosamine Sulfate Potassium double salt, and its molecular formula is (C
6h
13o
5n)
2hSO
4clKCl, 45.16g, productive rate 99.48%, product purity 99.79%, specific rotatory power [а]
d 25 ℃for+58.2 ° of (c2, H
2o).
Embodiment 2
40ml pure water and 440ml tetrahydrofuran (THF), after being uniformly mixed, be added in four-hole boiling flask, be warming up to 50 ℃, add 10.9g(0.08mol) sal enixum, 37.95g(0.176mol) glucosamine hydrochloride, stirring reaction 12h, controlling mixing speed is 160 revs/min; Then with ice-water bath, cool the temperature to 5 ℃ of insulation crystallization 5h, filter to obtain crystallisate; Crystallisate vacuum-drying 2.5h at 55 ℃ obtains Glucosamine Sulfate Potassium double salt 44.95g, and its molecular formula is (C
6h
13o
5n)
2hSO
4clKCl, productive rate 99.01%, product purity 98.25%, specific rotatory power [а]
d 25 ℃for+54.6 ° of (c2, H
2o).
Embodiment 3
400ml pure water and 6000ml tetrahydrofuran (THF), after being uniformly mixed, add in reactor, be warming up to 50 ℃, add 136.17g(1.0mol) sal enixum, 431.26g(2.0mol) glucosamine hydrochloride, stirring reaction 20h, controlling mixing speed is 180 revs/min; Then with ice-water bath, cool the temperature to 3 ℃ of insulation crystallization 6h, filter to obtain crystallisate; Crystallisate vacuum-drying 5h at 55 ℃ obtains Glucosamine Sulfate Potassium double salt 562.15g, and its molecular formula is (C
6h
13o
5n)
2hSO
4clKCl, productive rate 99.07%, product purity 98.7%, specific rotatory power [а]
d 25 ℃for+59.1 ° of (c2, H
2o).
Embodiment 4
40ml pure water and 400ml tetrahydrofuran (THF), after being uniformly mixed, be added in four-hole boiling flask, be warming up to 40 ℃, add 10.9g(0.08mol) sal enixum, 34.5g(0.16mol) glucosamine hydrochloride, stirring reaction 10h, controlling mixing speed is 150 revs/min; Then with ice-water bath, cool the temperature to 4 ℃ of insulation crystallization 3h, filter to obtain crystallisate; Crystallisate vacuum-drying 3.5h at 45 ℃ obtains Glucosamine Sulfate Potassium double salt 44.9g, and its molecular formula is (C
6h
13o
5n)
2hSO
4clKCl, productive rate 98.9%, product purity 99.12%, specific rotatory power [а]
d 25 ℃for+57.9 ° of (c2, H
2o).
Embodiment 5
40ml pure water and 520ml tetrahydrofuran (THF), after being uniformly mixed, be added in four-hole boiling flask, be warming up to 50 ℃, add 10.9g(0.08mol) sal enixum, 34.5g(0.16mol) glucosamine hydrochloride, stirring reaction 16h, controlling mixing speed is 140 revs/min; Then with ice-water bath, cool the temperature to 3 ℃ of insulation crystallization 5h, filter to obtain crystallisate; Crystallisate vacuum-drying 5h at 50 ℃ obtains Glucosamine Sulfate Potassium double salt 45.03g, productive rate 99.2%, product purity 99.65%, specific rotatory power [а]
d 25 ℃for+57.3 ° of (c2, H
2o).
In the Glucosamine Sulfate Potassium double salt that the present invention prepares, potassium content is lower, and the Glucosamine Sulfate Potassium double salt that the embodiment of the present invention 1～5 is prepared, respectively at 25 ℃, is placed 12 months under 60% relative humidity condition, still keeps stable; Under 40 ℃, 85% relative humidity condition, place that after 12 months, can to observe color slightly dimmed, the content of glucosamine slightly declines (about 3～4%), continues to place 12 months, and glucosamine content keeps stablizing constant.Illustrate that the Glucosamine Sulfate Potassium double salt obtaining produced according to the present invention has good chemical stability, nonhygroscopic under high humidity, not brown stain, preparation method are simple, and double salt product kind potassium content is low, meets medicinal standard.
Claims (6)
1. a preparation method for Glucosamine Sulfate Potassium double salt, is characterized in that comprising the steps:
(1) dose volume is than being the water of 1:10～15, tetrahydrofuran (THF) mixing solutions;
(2) be warming up to 30～60 ℃, the sal enixum that is 1.0:2.0～2.2 by mol ratio, glucosamine hydrochloride add in mixing solutions, stir 10～20h;
(3) be cooled to-5～5 ℃, crystallization 3～6h, filters to obtain crystallisate; At 40～60 ℃, vacuum-drying 0.5～5.0h obtains Glucosamine Sulfate Potassium double salt.
2. the preparation method of Glucosamine Sulfate Potassium double salt according to claim 1, is characterized in that: in step (1), and the volume ratio 1:12 of water, tetrahydrofuran (THF).
3. the preparation method of Glucosamine Sulfate Potassium double salt according to claim 1, is characterized in that: in step (2), the mol ratio of sal enixum, glucosamine hydrochloride is 1.0:2.0, and controlling mixing speed is 100～180 revs/min.
4. the preparation method of Glucosamine Sulfate Potassium double salt according to claim 1, is characterized in that: in step (3), adopt ice-water bath to lower the temperature, Tc is 2 ℃, and vacuum-drying temperature is 50 ℃.
5. the preparation method of Glucosamine Sulfate Potassium double salt according to claim 1, is characterized in that: described water is pure water.
6. the preparation method of Glucosamine Sulfate Potassium double salt according to claim 1, is characterized in that comprising the steps:
(1) dose volume is than being the water of 1:12, tetrahydrofuran (THF) mixing solutions;
(2) be warming up to 55 ℃, the sal enixum that is 1.0:2.0 by mol ratio, glucosamine hydrochloride add in mixing solutions, stir 15h; Wherein, controlling mixing speed is 170 revs/min;
(3) be cooled to-2 ℃, crystallization 4h, filters to obtain crystallisate; At 50 ℃, vacuum-drying 3h obtains Glucosamine Sulfate Potassium double salt.
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| CN201310620455.9A CN103601763B (en) | 2013-11-29 | 2013-11-29 | The preparation method of a kind of Glucosamine Sulfate Potassium double salt |
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| CN103601763B CN103601763B (en) | 2016-06-08 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866751A (en) * | 2017-02-17 | 2017-06-20 | 江苏双林海洋生物药业有限公司 | A kind of preparation method of Glucosamine Sulphate double salt |
| CN107827937A (en) * | 2017-10-27 | 2018-03-23 | 扬州日兴生物科技股份有限公司 | A kind of preparation method of Glucosamine sylvite |
| CN110305176A (en) * | 2019-06-28 | 2019-10-08 | 山东润德生物科技有限公司 | A kind of preparation method improving aminoglucose hydrochloride thermal stability |
| CN111471075A (en) * | 2020-05-09 | 2020-07-31 | 马鞍山市天泰生物科技有限公司 | Preparation method of glucosamine potassium sulfate particles |
| CN114853826A (en) * | 2022-05-12 | 2022-08-05 | 山西辅仁恒峰药业有限公司 | Preparation method of glucosamine sulfate sodium chloride double salt |
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| CN101066274A (en) * | 2007-05-28 | 2007-11-07 | 浙江澳兴生物科技有限公司 | Prepn process of double salt potassium D-aminogluconate sulfate |
| CN102167714A (en) * | 2011-03-02 | 2011-08-31 | 中国药科大学 | Quick and efficient method for preparing glucosamine sulfate potassium chloride compound salt |
| CN102850411A (en) * | 2012-10-12 | 2013-01-02 | 江苏澳新生物工程有限公司 | Preparation method of D-glucosamine sulfate potassium chloride salt |
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2013
- 2013-11-29 CN CN201310620455.9A patent/CN103601763B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030162732A1 (en) * | 2001-07-05 | 2003-08-28 | Astion Development A/S | Combination of aminosugars and cysteine or cysteine derivatives |
| CN101066274A (en) * | 2007-05-28 | 2007-11-07 | 浙江澳兴生物科技有限公司 | Prepn process of double salt potassium D-aminogluconate sulfate |
| CN102167714A (en) * | 2011-03-02 | 2011-08-31 | 中国药科大学 | Quick and efficient method for preparing glucosamine sulfate potassium chloride compound salt |
| CN102850411A (en) * | 2012-10-12 | 2013-01-02 | 江苏澳新生物工程有限公司 | Preparation method of D-glucosamine sulfate potassium chloride salt |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866751A (en) * | 2017-02-17 | 2017-06-20 | 江苏双林海洋生物药业有限公司 | A kind of preparation method of Glucosamine Sulphate double salt |
| CN106866751B (en) * | 2017-02-17 | 2019-11-05 | 江苏双林海洋生物药业有限公司 | A kind of preparation method of Glucosamine Sulphate double salt |
| CN107827937A (en) * | 2017-10-27 | 2018-03-23 | 扬州日兴生物科技股份有限公司 | A kind of preparation method of Glucosamine sylvite |
| CN110305176A (en) * | 2019-06-28 | 2019-10-08 | 山东润德生物科技有限公司 | A kind of preparation method improving aminoglucose hydrochloride thermal stability |
| CN111471075A (en) * | 2020-05-09 | 2020-07-31 | 马鞍山市天泰生物科技有限公司 | Preparation method of glucosamine potassium sulfate particles |
| CN114853826A (en) * | 2022-05-12 | 2022-08-05 | 山西辅仁恒峰药业有限公司 | Preparation method of glucosamine sulfate sodium chloride double salt |
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| CN103601763B (en) | 2016-06-08 |
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