CN101100435A - Method for preparing L-ornithine-L-aspartate - Google Patents
Method for preparing L-ornithine-L-aspartate Download PDFInfo
- Publication number
- CN101100435A CN101100435A CNA2006100285976A CN200610028597A CN101100435A CN 101100435 A CN101100435 A CN 101100435A CN A2006100285976 A CNA2006100285976 A CN A2006100285976A CN 200610028597 A CN200610028597 A CN 200610028597A CN 101100435 A CN101100435 A CN 101100435A
- Authority
- CN
- China
- Prior art keywords
- ornithine
- vitriol
- ratio
- resin
- filtering
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- IXUZXIMQZIMPSQ-ZBRNBAAYSA-N [(4s)-4-amino-4-carboxybutyl]azanium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound OC(=O)[C@@H](N)CCC[NH3+].[O-]C(=O)[C@@H](N)CC(O)=O IXUZXIMQZIMPSQ-ZBRNBAAYSA-N 0.000 title claims description 6
- 108010049063 ornithylaspartate Proteins 0.000 title claims description 6
- 238000000034 method Methods 0.000 title description 5
- 238000001914 filtration Methods 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 19
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims abstract description 14
- 239000011347 resin Substances 0.000 claims abstract description 12
- 229920005989 resin Polymers 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000012153 distilled water Substances 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- 229910001422 barium ion Inorganic materials 0.000 claims abstract description 4
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 38
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 20
- 229960003104 ornithine Drugs 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 17
- 239000000706 filtrate Substances 0.000 claims description 12
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 10
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 7
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 7
- 239000003456 ion exchange resin Substances 0.000 claims description 7
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 7
- 235000003704 aspartic acid Nutrition 0.000 claims description 6
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims description 4
- 238000009413 insulation Methods 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 239000003610 charcoal Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000001179 sorption measurement Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract 2
- WFZXUCAVKMKCSA-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid;sulfuric acid Chemical compound OS(O)(=O)=O.NCCC[C@H](N)C(O)=O WFZXUCAVKMKCSA-WCCKRBBISA-N 0.000 abstract 1
- 125000001214 L-asparto group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(O[H])=O 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 abstract 1
- 229910001863 barium hydroxide Inorganic materials 0.000 abstract 1
- 239000013522 chelant Substances 0.000 abstract 1
- 229920001429 chelating resin Polymers 0.000 abstract 1
- 238000004040 coloring Methods 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000012467 final product Substances 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- 150000001298 alcohols Chemical class 0.000 description 4
- 238000004064 recycling Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 150000008537 L-aspartic acids Chemical class 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003244 ornithine hydrochloride Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Production of L-2, 5-diaminovaleric acid-L-asparto salt by chemical synthesis is carried out by dissolving L-2, 5-diaminovaleric acid sulfate into distilled water, putting L-asparto, heating while dissolving, neutralizing sulfuric acid by barium hydroxide, cooling, filtering to remove diluted barium sulfate, chelating residual barium ion (Ba+2) by D403 chelate resin, filtering to remove chelating resin, decompressing while concentrating, de-coloring by activated carbon, filtering to remove activated carbon, agitating by anhydrous alcohol, heating, crystallizing under reflux state, filtering and drying to obtain final product. It avoids resin adsorption, resin recovery process and acid water treatment.
Description
Technical field:
The present invention relates to a kind of L-ornithine-preparation method, the especially chemical synthesis of L-aspartate and prepare the method for L-ornithine-L-aspartate.
Background technology:
The existing method for preparing L-ornithine-L-aspartate, 4 020 980 C1 make arginine change into ornithine with arginase as German patent DE, and in reaction process, regulate its PH with Aspartic Acid, and directly make this product.English Patent Brit.965 and for example, 637 and Brit.1,067,742 and European patent EP 0 477 991 A1, be raw material all,, use 3-5% ammoniacal liquor wash-out again through cationic exchange resin adsorption with the ornithine hydrochloride, the Aspartic Acid that adds equivalent after concentrating adds alcohols behind the reconcentration or acetone promptly gets product.Adopt the deficiency of aforesaid method to be: product yield is not high, only is about 50%, and the free ornithine of ion-exchange preparation need be used a large amount of resins, water loss is very big in the manipulation of regeneration, the sour water difficult treatment that is produced influences environment, is difficult to reach the target of suitability for industrialized production.
Summary of the invention:
The purpose of this invention is to provide the preparation method of a kind of L-ornithine-L-aspartate, avoided a large amount of use resins, to reduce the disposal of three wastes.
It is that 1: 7.8～8 ratio drops into L-ornithine vitriol in the distilled water than distilled water that the present invention is achieved in that in L-ornithine vitriol, after stirring and dissolving, is that 1: 0.68～0.70 ratio adds aspartic acid in L-ornithine vitriol than aspartic acid, be warming up to 45 ℃～50 ℃ through stirring heating, be incubated 10 minutes, press L-ornithine vitriol again than Ba (OH)
2.8H
2O (hydrated barta) is 1: 0.85～0.92 ratio adding Ba (OH)
28H
2O (hydrated barta), keep said temperature to stir 3～3.5 hours postcooling to room temperature, left standstill 6～7 hours, disgorging barium sulfate after filtration, stinging mould assembly vinylbenzene ion exchange resin in L-ornithine vitriol than the big space of D403 in filtrate is that 1: 0.10～0.12 ratio adds the big space of D403 chelating type vinylbenzene ion exchange resin, at room temperature stirred 1～1.5 hour, and removed chelating barium ion (Ba after filtration
+ 2) the D403 resin, its filtrate is when 45 ℃～50 ℃ vacuum decompressions are concentrated into feed concentration and are 1.20 grams per milliliters, in L-ornithine vitriol specific activity charcoal is that 1: 0.05 ratio adds gac, decoloured 30～40 minutes, after filtering, its filtrate heat temperature raising to 50 ℃ ± 2 ℃, add dehydrated alcohol in L-ornithine vitriol than 1: 0.26 ratio of dehydrated alcohol, insulation refluxed 3 hours, in stirring, drip dehydrated alcohol than 1: 1.3 ratio of dehydrated alcohol again in L-ornithine vitriol, be cooled to room temperature then and left standstill 1～1.5 hour, reclaim the ethanol product that must wet after filtration, at 60 ℃～65 ℃ dry down products.
The present invention is owing to adopt above-mentioned preparation method, avoided the sour water that produces in a large amount of use resins and the resin regeneration technique, the big space of employed D403 chelating type vinylbenzene ion exchange resin and dehydrated alcohol, all recyclable recycling, significantly reduced three wastes processing, for the suitability for industrialized production of product provides convenience.In addition, the present invention has work simplification, material cost and advantage of low energy consumption, and its yield can reach 76～80%, dry product content 〉=98.50%, specific rotatory power [α]
D 20+ 27 ° ± 1 °.
Embodiment:
Embodiment 1:
1, in the distilled water with 30.4 kilograms of 3.8 kilograms of inputs of L-ornithine vitriol, after the stirring and dissolving, drop into 2.66 kilograms of L-aspartic acids, stirring heating is warming up to 45 ℃～50 ℃, is incubated 10 minutes.
2, in above-mentioned established reactant, drop into Ba (OH)
28H
23.5 kilograms of O (hydrated barta), and keep said temperature to stir 3.5 hours postcooling to room temperature left standstill 7 hours, again disgorging barium sulfate after filtration.
3, add 0.45 kilogram in the big space of D403 chelating type vinylbenzene ion exchange resin in the filtrate of above-mentioned disgorging barium sulfate, at room temperature stir 1.5 hours after-filtration, its filter residue is the barium ion of the chelating (Ba of recyclable recycling
+ 2) the D403 resin, filtrate is concentrated to feed concentration when being 1.20 grams per milliliters in the dehydration of 50 ℃ of vacuum decompressions, adds 0.2 kilogram of gac, decolours 40 minutes.
4, elimination gac after filtration, its filtrate heat temperature raising to 50 ℃ ± 2 ℃ adds 0.988 kilogram of dehydrated alcohol, and insulation refluxed 3 hours, dripped 4.94 kilograms of dehydrated alcohols again in stirring, was cooled to room temperature then and left standstill 1.5 hours.Reclaim the ethanol product that must wet after filtration, 60 ℃～65 ℃ down dry 18 hours finished product.Product yield 80%, dry product content 99.0%, specific rotatory power [α]
D 20+ 26.8 °.
Embodiment 2:
1, in the distilled water with 296 kilograms of 38 kilograms of inputs of L-ornithine vitriol, after the stirring and dissolving, drop into 25.8 kilograms of L-aspartic acids, stirring heating is warming up to 45 ℃～50 ℃, is incubated 10 minutes.
2, in above-mentioned established reactant, drop into Ba (OH)
28H
232.3 kilograms of O (hydrated barta), and keep said temperature to stir 3 hours postcooling to room temperature left standstill 6 hours, again disgorging barium sulfate after filtration.
3, in the filtrate of above-mentioned disgorging barium sulfate, add 3.8 kilograms in the big space of D403 chelating type vinylbenzene ion exchange resin, at room temperature stir 1 hour after-filtration, its filter residue is the D403 resin of recyclable recycling, filtrate is concentrated to feed concentration when being 1.20 grams per milliliters in the dehydration of 50 ℃ of vacuum decompressions, add 2 kilograms of gacs, decoloured 30 minutes.
4, elimination gac after filtration, its filtrate heat temperature raising to 50 ℃ ± 2 ℃ adds 9.88 kilograms of dehydrated alcohols, and insulation refluxed 3 hours, dripped 49.4 kilograms of dehydrated alcohols again in stirring, was cooled to room temperature then and left standstill 1 hour.Reclaim the ethanol product that must wet after filtration, 60 ℃～65 ℃ down dry 18 hours finished product.Product yield 76.2%, dry product content 98.50%, specific rotatory power [α]
D 20+ 26.5 °.
Claims (1)
1, the preparation method of a kind of L-ornithine-L-aspartate is characterized in that:
Be that 1: 7.8～8 ratio drops into L-ornithine vitriol in the distilled water in L-ornithine vitriol than distilled water, after stirring and dissolving, is that 1: 0.68～0.70 ratio adds aspartic acid in L-ornithine vitriol than aspartic acid, be warming up to 45 ℃～50 ℃ through stirring heating, be incubated 10 minutes, press L-ornithine vitriol again than Ba (OH)
28H
2O (hydrated barta) is 1: 0.85～0.92 ratio adding Ba (OH)
28H
2O (hydrated barta), keep said temperature to stir 3～3.5 hours postcooling to room temperature, left standstill 6～7 hours, disgorging barium sulfate after filtration, in filtrate, be that 1: 0.10～0.12 ratio adds the big space of D403 chelating type vinylbenzene ion exchange resin than the big space of D403 chelating type vinylbenzene ion exchange resin in L-ornithine vitriol, at room temperature stirred 1～1.5 hour, and removed chelating barium ion (Ba after filtration
+ 2) the D403 resin, its filtrate is when 45 ℃～50 ℃ vacuum decompressions are concentrated into feed concentration and are 1.20 grams per milliliters, in L-ornithine vitriol specific activity charcoal is that 1: 0.05 ratio adds gac, decoloured 30～40 minutes, after filtering, its filtrate heat temperature raising to 50 ℃ ± 2 ℃, add dehydrated alcohol in L-ornithine vitriol than 1: 0.26 ratio of dehydrated alcohol, insulation refluxed 3 hours, in stirring, drip dehydrated alcohol than 1: 1.3 ratio of dehydrated alcohol again in L-ornithine vitriol, be cooled to room temperature then and left standstill 1～1.5 hour, reclaim the ethanol product that must wet after filtration, at 60 ℃～65 ℃ dry down products.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100285976A CN101100435A (en) | 2006-07-04 | 2006-07-04 | Method for preparing L-ornithine-L-aspartate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100285976A CN101100435A (en) | 2006-07-04 | 2006-07-04 | Method for preparing L-ornithine-L-aspartate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101100435A true CN101100435A (en) | 2008-01-09 |
Family
ID=39034914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100285976A Pending CN101100435A (en) | 2006-07-04 | 2006-07-04 | Method for preparing L-ornithine-L-aspartate |
Country Status (1)
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| CN (1) | CN101100435A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101843587A (en) * | 2010-04-30 | 2010-09-29 | 湖北荷普药业有限公司 | Method for preparing ornithine aspartate powder injection for injection |
| CN101844995A (en) * | 2010-05-13 | 2010-09-29 | 上海李氏化学科技有限公司 | Preparation method of L-ornithine-L-aspartate |
| CN102093236A (en) * | 2010-12-02 | 2011-06-15 | 海南美兰史克制药有限公司 | Ornithine aspartate compound and new preparation method thereof |
| CN102924311A (en) * | 2011-08-12 | 2013-02-13 | 北京四环制药有限公司 | L-ornithine-L-aspartate preparation method |
| CN108822003A (en) * | 2018-05-31 | 2018-11-16 | 成都市科隆化学品有限公司 | A kind of purifying technique of sulfosalicylic acid |
-
2006
- 2006-07-04 CN CNA2006100285976A patent/CN101100435A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101843587A (en) * | 2010-04-30 | 2010-09-29 | 湖北荷普药业有限公司 | Method for preparing ornithine aspartate powder injection for injection |
| CN101844995A (en) * | 2010-05-13 | 2010-09-29 | 上海李氏化学科技有限公司 | Preparation method of L-ornithine-L-aspartate |
| CN102093236A (en) * | 2010-12-02 | 2011-06-15 | 海南美兰史克制药有限公司 | Ornithine aspartate compound and new preparation method thereof |
| CN102093236B (en) * | 2010-12-02 | 2012-08-01 | 海南美兰史克制药有限公司 | Ornithine aspartate compound and new preparation method thereof |
| CN102924311A (en) * | 2011-08-12 | 2013-02-13 | 北京四环制药有限公司 | L-ornithine-L-aspartate preparation method |
| CN102924311B (en) * | 2011-08-12 | 2014-12-24 | 北京四环制药有限公司 | L-ornithine-L-aspartate preparation method |
| CN108822003A (en) * | 2018-05-31 | 2018-11-16 | 成都市科隆化学品有限公司 | A kind of purifying technique of sulfosalicylic acid |
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| AD01 | Patent right deemed abandoned |
Effective date of abandoning: 20080109 |
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