CN101591257B - Preparation method of crystal L-arginine L-aspartate - Google Patents
Preparation method of crystal L-arginine L-aspartate Download PDFInfo
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- CN101591257B CN101591257B CN2008100381169A CN200810038116A CN101591257B CN 101591257 B CN101591257 B CN 101591257B CN 2008100381169 A CN2008100381169 A CN 2008100381169A CN 200810038116 A CN200810038116 A CN 200810038116A CN 101591257 B CN101591257 B CN 101591257B
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Abstract
The invention relates to a preparation method of crystal L-arginine L-aspartate, comprising the following steps: preparing water solution of L-arginine, and slowly adding L-aspartic acid into the water solution, wherein the mol ratio of L-arginine and L-aspartic acid is 1:1; vacuum-concentrating at 50-80 DEG C after complete dissolution, removing water accounting for 20-60 percent of the total volume and cooling to 20-30 DEG C; slowly adding an organic hydrophilic solvent or a mixed solvent of a polar hydrophilic solvent and a non-polar hydrophilic solvent; and carrying out temperature reduction, crystallization, filtering, washing and vacuum drying to obtain the crystal L-arginine L-aspartate. Compared with the prior art, the invention has the advantages of reasonable process, simple steps, easy operation, good crystal form of the obtained product, difficult caking, convenient transportation and use, high purity (more than or equal to 98 percent) and high yield (80-86 percent) of the product, and the like, and is suitable for industrialization production.
Description
Technical field
The present invention relates to amino acid salts, relate in particular to a kind of preparation method of crystal L-arginine L-aspartate.
Background technology
The L-arginine L-aspartate is a kind of amidates healthcare products that sales volume increases day by day on the present world market, is mainly used in Ginseng Extract, enhances metabolism, strengthens body immunity etc.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-arginic acid salt, particularly to the research of the method for the salify crystallization of L-arginine L-aspartate.
At present, preparation method's complicated operation of crystal L-arginine L-aspartate, yield is low, is not suitable for suitability for industrialized production, can't satisfy growing demand, 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-arginine L-aspartate that a kind of technology is reasonable, simple to operate, crystal formation is good is provided for the defective that overcomes above-mentioned prior art existence.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of preparation method of crystal L-arginine L-aspartate is characterized in that, this method may further comprise the steps:
(1) the arginic aqueous solution of preparation L-slowly adds the L-aspartic acid in the arginic aqueous solution of L-, and the mol ratio of L-arginine and L-aspartic acid 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 be in the step (2) except 3～4 times of the volume that anhydrates, the joining day is 0.5～2.5 hour;
(4) with system cooling, crystallization, more after filtration, washing, vacuum-drying, obtain crystal L-arginine L-aspartate.
The concentration of the arginic aqueous solution of L-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 temperature of crystallization is 5～10 ℃ in the described step (4).
Vacuum drying temperature is 50～70 ℃ in the described step (4).
The present invention adopts the L-aspartic acid that adds equimolar amount in the L-arginine 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-arginine L-aspartate to the human body significant quantity.The protective foods acceptable carrier refers to 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 L-arginine L-aspartate of the present invention is by the crowd by oral administration to this nutritive food of needs.Be used for to be made into conventional solid preparation such as tablet, pulvis, granule, capsule etc. when oral, 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-arginine L-aspartate 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-arginine L-aspartate: in the 500ml reaction flask, adding 70ml (69.6g) content is the L-arginine solution (being equivalent to the 0.1molL-arginine) of 25% (weight), stir, slowly add 13.3g (0.1mol) L-aspartic acid, 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 56ml, 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 42ml, and the dropping time is 2hr, then the crystal solution temperature is down to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal 95% washing with alcohol, and 60 ℃ of vacuum-dryings, obtaining white plates crystal L-arginine L-aspartate (1: 1) 25g, yield is 81.4%, purity is 99.8%, [α]
D+ 25.9 ° (c=4,6N HCl).
Embodiment 2
A kind of preparation method of crystal L-arginine L-aspartate: in the 500ml reaction flask, adding 70ml (69.6g) content is the L-arginine solution (being equivalent to the 0.08molL-arginine) of 20% (weight), stir, slowly add 10.64g (0.08mol) L-aspartic acid, 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 28ml, 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 168ml, and the dropping time is 2.5hr, then the crystal solution temperature is down to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with anhydrous methanol, and 50 ℃ of vacuum-dryings, obtaining white plates crystal L-arginine L-aspartate (1: 1) 19.7g, yield is 80.4%, purity is 99.5%, [α]
D+ 26.8 ° (c=4,6N HCl).
Embodiment 3
A kind of preparation method of crystal L-arginine L-aspartate: in the 500ml reaction flask, adding 70ml (69.6g) content is the L-arginine solution (being equivalent to the 0.12molL-arginine) of 30% (weight), stir, slowly add 15.96g (0.12mol) L-aspartic acid, 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 49ml, 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 63ml, and the dropping time is 2hr, then the crystal solution temperature is down to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with isopropylcarbinol, and 70 ℃ of vacuum-dryings, obtaining white plates crystal L-arginine L-aspartate (1: 1) 30.5g, yield is 82.8%, purity is 98.6%, [α]
D+ 26.3 ° (c=4,6N HCl).
Embodiment 4
A kind of preparation method of crystal L-arginine L-aspartate: in the 500ml reaction flask, adding 70ml (69.6g) content is the L-arginine solution (being equivalent to the 0.1molL-arginine) of 25% (weight), stir, slowly add 13.3g (0.1mol) L-aspartic acid, 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 42ml, be cooled to 25 ℃, slowly drip the mixed solvent propyl alcohol while stirring: normal hexane (1: 1), mixed solvent total amount are 112ml, and the dropping time is 0.5hr, then the crystal solution temperature is down to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with above-mentioned mixed solvent, and 60 ℃ of vacuum-dryings, obtaining white plates crystal L-arginine L-aspartate (1: 1) 26.4g, yield is 86.0%, purity is 98.0%, [α]
D+ 27.2 ° (c=4,6N HCl).
Embodiment 5
A kind of preparation method of crystal L-arginine L-aspartate: in the 500ml reaction flask, adding 70ml (69.6g) content is the L-arginine solution (being equivalent to the 0.1molL-arginine) of 25% (weight), stir, slowly add 13.3g (0.1mol) L-aspartic acid, 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 42ml, be cooled to 30 ℃, slowly drip mixed solvent methyl alcohol while stirring: sherwood oil (5: 1), mixed solvent total amount are 84ml, and the dropping time is 40min, then the crystal solution temperature is down to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal washs with above-mentioned mixed solvent, and 60 ℃ of vacuum-dryings, obtaining white plates crystal L-arginine L-aspartate (1: 1) 26.4g, yield is 86.0%, purity is 99.2%, [α]
D+ 27.2 ° (c=4,6N HCl).
Claims (7)
1. the preparation method of a crystal L-arginine L-aspartate is characterized in that, this method may further comprise the steps:
(1) the arginic aqueous solution of preparation L-slowly adds the L-aspartic acid in the arginic aqueous solution of L-, and the mol ratio of L-arginine and L-aspartic acid 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 be in the step (2) except 3 ~ 4 times of the volume that anhydrates, the joining day is 0.5 ~ 2.5 hour;
(4) with system cooling, crystallization, more after filtration, washing, vacuum-drying, obtain crystal L-arginine L-aspartate.
2. the preparation method of a kind of crystal L-arginine L-aspartate according to claim 1 is characterized in that, the concentration of the arginic aqueous solution of L-is 20wt% ~ 30wt% in the described step (1).
3. the preparation method of a kind of crystal L-arginine L-aspartate according to claim 1 is characterized in that, in the described step (2), and after dissolving fully, 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-arginine L-aspartate 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-arginine L-aspartate 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-arginine L-aspartate according to claim 1 is characterized in that, the temperature of crystallization is 5 ~ 10 ℃ in the described step (4).
7. the preparation method of a kind of crystal L-arginine L-aspartate according to claim 1 is characterized in that, vacuum drying temperature is 50 ~ 70 ℃ in the described step (4).
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| CN102102118B (en) * | 2009-12-18 | 2012-08-15 | 上海汉飞生化科技有限公司 | Method for preparing L-ornithine-L-aspartate salt |
| CN105935139A (en) * | 2015-11-18 | 2016-09-14 | 浙江荣信生物科技有限公司 | L-arginine-L-aspartate and preparation technology thereof |
| CN108689887A (en) * | 2018-04-23 | 2018-10-23 | 宜兴市前成生物有限公司 | A kind of method of industrialized production L-arginine-ASPARTIC ACID |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5227007A (en) * | 1990-09-28 | 1993-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing crystals of salt of acidic amino acid and basic amino acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US5227007A (en) * | 1990-09-28 | 1993-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing crystals of salt of acidic amino acid and basic amino acid |
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Owner name: HUNAN TIANCHENG BIOCHEMICAL TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: SHANGHAI HANFEI BIOCHEMICAL SCIENCE + TECHNOLOGY CO., LTD. Effective date: 20150605 |
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