CN101591264A - A kind of preparation method of crystal L-glutamine alpha-ketoglutarate - Google Patents
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate Download PDFInfo
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- CN101591264A CN101591264A CNA2008100381154A CN200810038115A CN101591264A CN 101591264 A CN101591264 A CN 101591264A CN A2008100381154 A CNA2008100381154 A CN A2008100381154A CN 200810038115 A CN200810038115 A CN 200810038115A CN 101591264 A CN101591264 A CN 101591264A
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Abstract
The present invention relates to a kind of preparation method of crystal L-glutamine alpha-ketoglutarate, this method comprises: the aqueous solution of preparation L-glutaminate, slowly α-Tong Wuersuan is added wherein, the mol ratio of L-glutaminate and α-Tong Wuersuan is 1: 1; After dissolving fully, 50～80 ℃ of following concentrating under reduced pressure, the water yield of removing cumulative volume 20%～60% is cooled to 20～30 ℃; Slowly add organic hydrophilic solvent, the perhaps mixed solvent of polar hydrophilic solvent and non-polar solvent; Cooling, crystallization more after filtration, washing, vacuum-drying, obtain crystal L-glutamine alpha-ketoglutarate.Compared with prior art, technology of the present invention is reasonable, and step is simple, processing ease, the product crystal formation of gained is good, prevented from caking, be convenient to transportation and use, also have purity height (〉=98%), the yield height advantages such as (80～86%) of product simultaneously, be adapted to suitability for industrialized production.
Description
Technical field
The present invention relates to amino acid salts, relate in particular to a kind of preparation method of crystal L-glutamine alpha-ketoglutarate.
Background technology
The L-glutaminate alpha-ketoglutarate is a kind of amidates healthcare products that sales volume increases day by day on the present world market, as nutritional supplement.Growing along with the international market demand amount becomes the emphasis that people pay close attention to the research of the crystallization method of L-glutaminate salt, particularly to the research of the salify crystalline method of L-glutaminate α-Tong Wuersuan.
At present, the preparation method of L-glutaminate alpha-ketoglutarate does not have systematic account, and is especially described very few for the technology of suitability for industrialized production, and product also exists shortcomings such as purity is low, crystal formation is not good simultaneously.
Summary of the invention
Purpose of the present invention is exactly the preparation method that the crystal L-glutamine alpha-ketoglutarate that a kind of technology is reasonable, simple to operate, crystal formation is good is provided for suitability for industrialized production.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate is characterized in that, this method may further comprise the steps:
(1) aqueous solution of preparation L-glutaminate slowly adds α-Tong Wuersuan in the aqueous solution of L-glutaminate, and the mol ratio of L-glutaminate and α-Tong Wuersuan is 1: 1;
(2) fully the dissolving after, 50～80 ℃ of following concentrating under reduced pressure, the water yield of removing cumulative volume 20%～60% is cooled to 20～30 ℃;
(3) slowly add organic hydrophilic solvent, the perhaps mixed solvent of polar hydrophilic solvent and non-polar solvent, the adding total amount is to remove 3～4 times of the volume that anhydrates in the step (2), the joining day is 0.5～2.5 hour;
(4), more after filtration, washing, vacuum-drying, obtain crystal L-glutamine alpha-ketoglutarate with system cooling, crystallization.
The concentration of the aqueous solution of L-glutaminate is 20%～30% (weight) in the described step (1).
In the described step (2), after dissolving fully, 55 ℃ of following concentrating under reduced pressure, the water yield of removing cumulative volume 30%～40% is cooled to 22～25 ℃.
Organic hydrophilic solvent is selected from a kind of in methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the isopropylcarbinol in the described step (3).
The volume ratio of mixed solvent Semi-polarity hydrophilic solvent and non-polar solvent is 1～5: 1 in the described step (3), described polar hydrophilic solvent is selected from a kind of in methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the isopropylcarbinol, and described non-polar solvent is selected from sherwood oil, the normal hexane a kind of.
The crystalline temperature is 5～10 ℃ in the described step (4).
Vacuum drying temperature is 50～70 ℃ in the described step (4).
The present invention adopts the α-Tong Wuersuan that adds equimolar amount in the L-glutaminate aqueous solution, at ambient temperature, the reaction salify, then under 50～80 ℃ temperature condition, concentrating under reduced pressure is removed the water that is equivalent to cumulative volume 20～60%, add hydrophilic organic solvent or mixed solvent again, obtain product 20～30 ℃ of crystallizations, reaction formula is as follows:
Product of the present invention can mix with acceptable carrier on one or more protective foodss according to the production method of field of health care food routine, obtains containing the various formulations of L-glutaminate alpha-ketoglutarate to the human body significant quantity.The protective foods acceptable carrier is meant conventional protective foods carrier, and for example: thinner, vehicle etc. can also add other assistant agent and flavouring agent, sweeting agent etc. in addition; Its dosage form comprises various solid dosages and liquid dosage form.
Product crystal L-glutamine alpha-ketoglutarate of the present invention is by the crowd by oral administration to this nutritive food of needs.Be used for when oral, can be made into conventional solid preparation such as tablet, pulvis, granule, capsule etc., also can be made into liquid preparation such as water or oiliness suspension agent etc. or other liquid preparation such as syrup etc.; Preferred form is tablet, coated tablet, capsule etc.
Compared with prior art, preparation method's technology of crystal L-glutamine alpha-ketoglutarate of the present invention is reasonable, step is simple, processing ease, the product crystal formation of gained is good, and prevented from caking is convenient to transportation and use, also have purity height (〉=98%), the yield height advantages such as (80～86%) of product simultaneously, be adapted to suitability for industrialized production.
Embodiment
The invention will be further described below in conjunction with specific embodiment.
Embodiment 1
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate: in the 500ml reaction flask, adding 72.5ml (73g) content is the L-glutaminate solution (being equivalent to the 0.1molL-glutamine) of 20% (weight), stir, slowly add 14.6g (0.1mol) α-Tong Wuersuan, room temperature reaction 10mins, dissolving, concentrating under reduced pressure then fully, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is cooled to 23 ℃ to the 43.5ml, slowly drips 95% ethanol while stirring when having small amount of crystalline to separate out, stir 10mins, continue then to drip 95% ethanol, the ethanol total amount is 116ml, and the dropping time is 2.5hr, then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal 95% washing with alcohol, and, obtaining white plates crystal L-glutamine alpha-ketoglutarate (1: 1) 23.7g 60 ℃ of vacuum-dryings, yield is 81.4%, purity is 99.8%, [α]
D+ 18.6 ° (c=4,6N HCl).
Embodiment 2
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate: in the 500ml reaction flask, adding 72.5ml (73g) content is the L-glutaminate solution (being equivalent to the 0.15molL-glutamine) of 30% (weight), stir, slowly add 21.9g (0.15mol) α-Tong Wuersuan, room temperature reaction 10mins, dissolving, concentrating under reduced pressure then fully, 50 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is cooled to 20 ℃ to the 58ml, slowly drips anhydrous methanol while stirring when having small amount of crystalline to separate out, stir 10mins, continue then to drip anhydrous methanol, the methyl alcohol total amount is 43.5ml, and the dropping time is 2hr, then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with anhydrous methanol, and, obtaining white plates crystal L-glutamine alpha-ketoglutarate (1: 1) 35.2g 50 ℃ of vacuum-dryings, yield is 80.4%, purity is 99.5%, [α]
D+ 17.3 ° (c=4,6N HCl).
Embodiment 3
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate: in the 500ml reaction flask, adding 72.5ml (73g) content is the L-glutaminate solution (being equivalent to the 0.1molL-glutamine) of 20% (weight), stir, slowly add 14.6g (0.1mol) α-Tong Wuersuan, room temperature reaction 10mins, dissolving, concentrating under reduced pressure then fully, 80 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is cooled to 22 ℃ to the 29ml, slowly drips isopropylcarbinol while stirring when having small amount of crystalline to separate out, stir 10mins, continue then to drip isopropylcarbinol, the isopropylcarbinol total amount is 174ml, and the dropping time is 2hr, then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with isopropylcarbinol, and, obtaining white plates crystal L-glutamine alpha-ketoglutarate (1: 1) 24.1g 70 ℃ of vacuum-dryings, yield is 82.8%, purity is 98.6%, [α]
D+ 17.9 ° (c=4,6N HCl).
Embodiment 4
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate: in the 500ml reaction flask, adding 72.5ml (73g) content is the L-glutaminate solution (being equivalent to the 0.1molL-glutamine) of 20% (weight), stir, slowly add 14.6g (0.1mol) α-Tong Wuersuan, room temperature reaction 10mins, dissolving fully, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 50.75ml, be cooled to 25 ℃, slowly drip the mixed solvent propyl alcohol while stirring: normal hexane (1: 1), mixed solvent total amount are 65.25ml, and the dropping time is 0.5hr, then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with above-mentioned mixed solvent, and, obtaining white plates crystal L-glutamine alpha-ketoglutarate (1: 1) 25.0g 60 ℃ of vacuum-dryings, yield is 86.0%, purity is 99.2%, [α]
D+ 18.5 ° (c=4,6N HCl).
Embodiment 5
A kind of preparation method of crystal L-glutamine alpha-ketoglutarate: in the 500ml reaction flask, adding 72.5ml (73g) content is the L-glutaminate solution (being equivalent to the 0.1molL-glutamine) of 20% (weight), stir, slowly add 14.6g (0.1mol) α-Tong Wuersuan, room temperature reaction 10mins, dissolving fully, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 43.5ml, be cooled to 30 ℃, slowly drip mixed solvent methyl alcohol while stirring: sherwood oil (5: 1), mixed solvent total amount are 87ml, and the dropping time is 40min, then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with above-mentioned mixed solvent, and, obtaining white plates crystal L-glutamine alpha-ketoglutarate (1: 1) 25.0g 60 ℃ of vacuum-dryings, yield is 86.0%, purity is 99.2%, [α]
D+ 18.5 ° (c=4,6N HCl).
Claims (7)
1. the preparation method of a crystal L-glutamine alpha-ketoglutarate is characterized in that, this method may further comprise the steps:
(1) aqueous solution of preparation L-glutaminate slowly adds α-Tong Wuersuan in the aqueous solution of L-glutaminate, and the mol ratio of L-glutaminate and α-Tong Wuersuan is 1: 1;
(2) fully the dissolving after, 50～80 ℃ of following concentrating under reduced pressure, the water yield of removing cumulative volume 20%～60% is cooled to 20～30 ℃;
(3) slowly add organic hydrophilic solvent, the perhaps mixed solvent of polar hydrophilic solvent and non-polar solvent, the adding total amount is to remove 3～4 times of the volume that anhydrates in the step (2), the joining day is 0.5～2.5 hour;
(4), more after filtration, washing, vacuum-drying, obtain crystal L-glutamine alpha-ketoglutarate with system cooling, crystallization.
2. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1 is characterized in that, the concentration of the aqueous solution of L-glutaminate is 20%～30% (weight) in the described step (1).
3. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1 is characterized in that, in the described step (2), fully after the dissolving, 55 ℃ of following concentrating under reduced pressure, the water yield of removing cumulative volume 30%～40% is cooled to 22～25 ℃.
4. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1 is characterized in that, organic hydrophilic solvent is selected from a kind of in methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the isopropylcarbinol in the described step (3).
5. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1, it is characterized in that, the volume ratio of mixed solvent Semi-polarity hydrophilic solvent and non-polar solvent is 1～5: 1 in the described step (3), described polar hydrophilic solvent is selected from a kind of in methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the isopropylcarbinol, and described non-polar solvent is selected from sherwood oil, the normal hexane a kind of.
6. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1 is characterized in that, the crystalline temperature is 5～10 ℃ in the described step (4).
7. the preparation method of a kind of crystal L-glutamine alpha-ketoglutarate according to claim 1 is characterized in that, vacuum drying temperature is 50～70 ℃ in the described step (4).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112321676A (en) * | 2020-12-12 | 2021-02-05 | 山东诚汇双达药业有限公司 | Salt forming method of neotame |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101037400A (en) * | 2006-08-11 | 2007-09-19 | 上海汉飞生化科技有限公司 | Preparation method of L-Ornithine-Malic Acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101037400A (en) * | 2006-08-11 | 2007-09-19 | 上海汉飞生化科技有限公司 | Preparation method of L-Ornithine-Malic Acid |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321676A (en) * | 2020-12-12 | 2021-02-05 | 山东诚汇双达药业有限公司 | Salt forming method of neotame |
| CN112321676B (en) * | 2020-12-12 | 2022-06-14 | 山东诚汇双达药业有限公司 | Salt forming method of neotame |
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Application publication date: 20091202 |