CN101037400A - Preparation method of L-Ornithine-Malic Acid - Google Patents
Preparation method of L-Ornithine-Malic Acid Download PDFInfo
- Publication number
- CN101037400A CN101037400A CN 200610029943 CN200610029943A CN101037400A CN 101037400 A CN101037400 A CN 101037400A CN 200610029943 CN200610029943 CN 200610029943 CN 200610029943 A CN200610029943 A CN 200610029943A CN 101037400 A CN101037400 A CN 101037400A
- Authority
- CN
- China
- Prior art keywords
- citrulline
- malic acid
- acid
- oxysuccinic acid
- sherwood oil
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title description 7
- XSVCLOQAJFLBSB-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid;2-hydroxybutanedioic acid Chemical compound NCCC[C@H](N)C(O)=O.OC(=O)C(O)CC(O)=O XSVCLOQAJFLBSB-WCCKRBBISA-N 0.000 title 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims abstract description 35
- 229960002173 citrulline Drugs 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 17
- 238000002425 crystallisation Methods 0.000 claims abstract description 13
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 230000008025 crystallization Effects 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000012454 non-polar solvent Substances 0.000 claims abstract description 4
- 238000005406 washing Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 239000002253 acid Substances 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 11
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 10
- 229940116298 l- malic acid Drugs 0.000 claims description 9
- 229940099690 malic acid Drugs 0.000 claims description 9
- 239000001630 malic acid Substances 0.000 claims description 9
- 235000011090 malic acid Nutrition 0.000 claims description 9
- 239000012046 mixed solvent Substances 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 abstract description 8
- DROVUXYZTXCEBX-WCCKRBBISA-N (2s)-2-amino-5-(carbamoylamino)pentanoic acid;2-hydroxybutanedioic acid Chemical compound OC(=O)C(O)CC(O)=O.OC(=O)[C@@H](N)CCCNC(N)=O DROVUXYZTXCEBX-WCCKRBBISA-N 0.000 abstract description 4
- 238000001035 drying Methods 0.000 abstract description 2
- 238000005054 agglomeration Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 229940049920 malate Drugs 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 28
- 239000013078 crystal Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 230000001186 cumulative effect Effects 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- 229930064664 L-arginine Natural products 0.000 description 3
- 235000014852 L-arginine Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- RUFJTBOKWJYXPM-WCCKRBBISA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;2-hydroxybutanedioic acid Chemical compound OC(=O)C(O)CC(O)=O.OC(=O)[C@@H](N)CCCN=C(N)N RUFJTBOKWJYXPM-WCCKRBBISA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 235000009697 arginine 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229940071125 manganese acetate Drugs 0.000 description 1
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a producing method for L-citrulline-malate, comprising the steps of: slowly adding 20-30% L-citrulline into malate with a molar rate of 1:1 or 2:1; in 50-80 DEG C, decompress and concentrating and cooling down to 20-30 DEG C; slowly adding organic solvent or a mixing solvent of polar hydrophilic solvent and non-polar solvent, cooling crystallization, filtering and washing, drying in vaccum to get finished product. The method has simple steps, a high product purity, a high yield and is not tending to agglomeration, facilitates to transportation and application and fits for industrialisation.
Description
Technical field
The present invention relates to L MALIC ACID and amino acid whose crystallization method, be specifically related to L-citrulline-method of preparing malic acid.
Background technology
L-citrulline-malate is a kind of amidates healthcare products that sales volume increases day by day on the present world market, is mainly used in diet products.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-citrulline salt, particularly to the research of the salify crystalline method of L-citrulline-L MALIC ACID.
Patents such as day disclosure 54-143603,54-42378, US4420432, US4438044 series have been reported L MALIC ACID and multiple amino acids reaction salify crystallization method.Wherein L MALIC ACID and other amino acid salify crystallization method, as follows as the salt-forming reaction formula of L-arginine-DL-malate (2: 1):
L-arginine-DL-oxysuccinic acid (2: 1) reactions steps is as follows:
The DL-oxysuccinic acid slowly is added in the L-arginine aqueous solution (according to mol ratio), is evaporated to state of saturation (spend the night under the room temperature do not have crystal separate out); Add crystal seed then, add the methyl alcohol precipitating and spend the night, filter, the filter cake methanol wash, drying can get finished product.During other amino acid salifies, do not add under the situation of crystal seed, organic solvent adds in batches, and the primary sedimentation crystallization gets product.
But about oxysuccinic acid and L-citrulline reaction salify crystallization method, has only CA summary V82:P144952c, a kind of crystallization method briefly is provided, this kind method is the utilization Freeze Drying Technique, need the requirement of mechanical means, and the quantity of solvent of obtain solution is big, makes to be unwell to suitability for industrialized production by the preparation cost height.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of L-citrulline-method of preparing malic acid.This method steps is simple, the product purity height, and the yield height is adapted to suitability for industrialized production.
Reaction formula of the present invention is as follows:
Wherein: n=1,2
Reactions steps of the present invention is as follows:
1. prepare the aqueous solution of 20%～30%L-citrulline, slowly oxysuccinic acid is added in the L-citrulline solution L-citrulline: oxysuccinic acid mol ratio 1: 1 or 2: 1;
2. after treating to dissolve fully, under 50～80 ℃ temperature, concentrating under reduced pressure is removed and is equivalent to 20～60% the water yield, is cooled to 20～30 ℃;
3 slowly add hydrophilic organic solvents to a small amount of crystallizations separates out, and stirs 10～15 minutes, continues slowly to add organic solvent, adds total amount and is equivalent to except that the volume that anhydrates 3～4 times, and the joining day was at 2～2.5 hours; The mixed solvent of perhaps disposable slow adding polar hydrophilic solvent and non-polar solvent, the joining day, the adding total amount was the same at 30～40 minutes;
4 cooling post crystallizations, filtration washing, 60 ℃ of vacuum-dryings obtain finished product.
Preferably 55 ℃ of concentrating under reduced pressure bath temperatures are removed the water that is equivalent to cumulative volume 30～40% and are most suited to crystalline concentration, and best Tc is 22～25 ℃.
Hydrophilic organic solvent comprises methyl alcohol, ethanol, propyl alcohol, Virahol, butanols and isopropylcarbinol, and the mixed solvent of polar hydrophilic solvent and non-polar solvent comprises methyl alcohol: sherwood oil, methyl alcohol: normal hexane, ethanol: sherwood oil, ethanol: normal hexane, propyl alcohol: sherwood oil, propyl alcohol: normal hexane, Virahol: sherwood oil, Virahol: normal hexane, propyl carbinol: sherwood oil, propyl carbinol: normal hexane, isopropylcarbinol: sherwood oil and isopropylcarbinol: normal hexane.
The characteristics of present method are with mol or 0.5 molar oxysuccinic acid (L such as adding in the homemade L-citrulline aqueous solution, DL), 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%, adds hydrophilic organic solvent or mixed solvent again, obtains product 20～30 ℃ of crystallizations.
Present method is better more in batches than the product crystal formation that adds solvent once crystallization gained, and prevented from caking is convenient to transportation and use, and method is simple, product purity height (〉=98%), and yield height (80～86%) is adapted to suitability for industrialized production.
The present invention contains the effective above-mentioned L-citrulline-oxysuccinic acid of human body, and contains acceptable carrier on one or more protective foodss.
Above-mentioned protective foods acceptable carrier is meant conventional protective foods carrier, for example: thinner, vehicle etc.Its dosage form comprises various solid dosages and liquid dosage form.Can also add other assistant agent and flavouring agent, sweeting agent etc. in addition.
L-citrulline-oxysuccinic acid 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., make 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.
The various formulations of the present invention can for example make L-citrulline-oxysuccinic acid active ingredient mix with one or more carriers according to the production method preparation of field of health care food routine.
The preparation method of L-citrulline is as follows::
1 adds L-arginine 75g in the reaction flask of 500ml, distilled water 300ml stirs under the room temperature, transfers about pH9.45～9.55 with dense HCl, and repetition measurement pH behind the stirring 30mins raises as the pH value, transfers to about 9.50 with dense HCl.Add enzyme powder 2g, manganese acetate 0.3g is warming up to 50～52 ℃, stirring reaction 16hr.To there not being the arginine spot, reaction finishes with the TLC monitoring.Add 50%H
2SO
4Transfer pH5.0～6.0, add the 2g gac, be warming up to 90 ℃, stir 30mins, filter a small amount of distilled water wash of filter cake.Merging filtrate, concentrating under reduced pressure, remove half volume after, the cooling, obtain colourless or pale yellow solution.
In the 2 above-mentioned reaction solutions, add the 118g cupric sulfate pentahydrate, 103g urea stirs, and transfers pH6.5～7.0 with 10%NaOH, heats up, and normal pressure concentrates, and oil bath temperature is controlled at about 110～120 ℃.This moment, the reaction solution color was become light bluely gradually by mazarine, and had a large amount of blue solids to separate out.Reaction is extremely monitored no ornithine spot through TLC, termination reaction, and the time is about 6hr.
3 above-mentioned reacting liquid filterings are used the distilled water wash filter cake, obtain L-citrulline mantoquita.L-citrulline mantoquita is placed three-necked bottle, add the distilled water (V/W) of 5 times of amounts, stir on the limit, and the limit feeds H
2S gas does not produce to there being CuS, stops to feed H
2S changes bubbling air and drives away remaining H in the reaction solution
2S gas.In reaction solution, add the 3g gac then, stir 30mins under the room temperature, filter, a small amount of distilled water wash of filter cake, merging filtrate is transferred pH6.5～7.0, and pressurization concentrates, 60 ℃ of bath temperatures.Steam the water of half volume approximately, control solution L-citrulline concentration stops to concentrate about 20～30%, obtains flaxen L-citrulline solution, and it is standby to place refrigerator.
TLC monitoring wherein: get the solution example that needs monitoring in the experiment, other gets corresponding reference substance solution (as the L-arginine, L-ornithine standard specimen), draws above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with n-propyl alcohol: strong aqua (67: 33) is a developping agent, after the expansion, dries, at 90 ℃ of dry 10mins, spray at 90 ℃ of dry 10mins, is inspected immediately with ninhydrin solution (1 → 50) again.Institute's test sample product solution is as showing the color of impurity spot, with the principal spot of reference substance solution relatively, must not be darker.
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment
Embodiment 1
In the 500ml reaction flask, adding 140ml content is 25% L-citrulline solution (being equivalent to 0.2mol), stirs, slowly add 13.4g (0.1mol) L MALIC ACID, at room temperature reaction 10mins, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 95ml, and cooling temperature to 23 ℃ slowly drips 95% ethanol when having small amount of crystalline to separate out while stirring, stir 10mins, continue then to drip 95% ethanol, the ethanol total amount is about 180ml, and the dropping time is 2hr.Then the crystal solution temperature is reduced to 5～10 ℃, place 30mins, make crystal structure complete, filter, crystal 95% washing with alcohol, and obtain white plates crystal type L-citrulline-L MALIC ACID salt (2: 1) (39.4g, yield: 81.4%) 60 ℃ of vacuum-dryings.
[a]
D+19.5(c＝4，6N?HCl)
Ultimate analysis: (C
6H
13N
3O
3)
2C
4H
6O
5
Calculated value: C 39.67% H 6.61% N 17.36%
Test value: C 39.78% H 6.73% N 17.24%
Content: 99.8% (, extrapolating product content more thus) with NaOH solution titration oxysuccinic acid
Embodiment 2
In the 500ml reaction flask, adding 70ml content is 25% L-citrulline solution (being equivalent to 0.1mol), stirs, slowly add 13.4g (0.1mol) DL-oxysuccinic acid, at room temperature reaction 10mins, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 44ml, and cooling temperature to 23 ℃ slowly drips anhydrous methanol when having small amount of crystalline to separate out while stirring, stir 10mins, continue then to drip anhydrous methanol, the methyl alcohol total amount is about 90ml, 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 obtains white plates crystal type L-citrulline-DL-malate (1: 1) (24.8g, yield: 80.4%) 60 ℃ of vacuum-dryings.
[a]
D+15.6°(c＝4，6N?HCl)
Ultimate analysis: C
6H
13N
3O
3C
4H
6O
5
Calculated value: C 38.83% H 6.15% N 13.59%
Test value: C 38.89% H 6.13% N 13.51%
Content: 99.5% (, extrapolating product content more thus) with NaOH solution titration oxysuccinic acid
Embodiment 3
In the 500ml reaction flask, adding 70ml content is 25% L-citrulline solution (being equivalent to 0.1mol), stirs, slowly add 13.4g (0.1mol) L MALIC ACID, at room temperature reaction 10mins, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 45ml, and cooling temperature to 23 ℃ slowly drips isopropylcarbinol when having small amount of crystalline to separate out while stirring, stir 10mins, continue then to drip isopropylcarbinol, the isopropylcarbinol total amount is about 100ml, 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 obtains white plates crystal type L-citrulline-L MALIC ACID salt (1: 1) (25.6g, yield: 82.8%) 60 ℃ of vacuum-dryings.
[a]
D+16.0°(c＝4，6N?HCl)
Ultimate analysis: C
6H
13N
3O
3C
4H
6O
5
Calculated value: C 38.83% H 6.15% N 13.59%
Test value: C 38.62% H 6.33% N 13.44%
Content: 98.6% (, extrapolating product content more thus) with NaOH solution titration oxysuccinic acid
Embodiment 4
In the 500ml reaction flask, adding 140ml content is 25% L-citrulline solution (being equivalent to 0.2mol), stirs, and slowly adds 13.4g (0.1mol) DL-oxysuccinic acid, at room temperature reaction 10mins, concentrating under reduced pressure then, 55 ℃ of bath temperatures, the concentration of reaction solution cumulative volume is to the 90ml, cooling temperature to 23 ℃, slowly drip the mixed solvent propyl alcohol while stirring: normal hexane, total amount are about 175ml, 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 mixed solvent, and obtains white plates crystal type L-citrulline-DL-malate (2: 1) (41.6g, yield: 86.0%) 60 ℃ of vacuum-dryings.
[a]
D+18.5°(c＝4，6N?HCl)
Ultimate analysis: (C
6H
13N
3O
3)
2C
4H
6O
5
Calculated value: C 39.67% H 6.61% N 17.36%
Test value: C 39.58% H 6.67% N 17.25%
Content: 98.0% (, extrapolating product content more thus) with NaOH solution titration oxysuccinic acid.
Claims (6)
1. L-citrulline-method of preparing malic acid is characterized in that: comprise that step is as follows:
(1) 20%～30%L-citrulline aqueous solution slowly adds oxysuccinic acid,
L-citrulline: oxysuccinic acid mol ratio 1: 1 or 2: 1;
(2) after the dissolving, under 50～80 ℃ temperature, concentrating under reduced pressure is removed and is equivalent to 20～60% the water yield, is cooled to 20～30 ℃;
(3) slowly add the mixed solvent of organic solvent or polar hydrophilic solvent and non-polar solvent, total amount is equivalent to remove 3～4 times of the volume that anhydrates, 0.5～2.5 hour time;
(4) decrease temperature crystalline, filtration washing, vacuum-drying.
2. a kind of L-citrulline-method of preparing malic acid as claimed in claim 1 is characterized in that: oxysuccinic acid is L MALIC ACID or DL-oxysuccinic acid.
3. a kind of L-citrulline-method of preparing malic acid as claimed in claim 1, it is characterized in that: the concentrating under reduced pressure temperature is 55 ℃, removes to be equivalent to 30～40% water, Tc is 22～25 ℃.
4. a kind of L-citrulline-method of preparing malic acid as claimed in claim 1, it is characterized in that: organic solvent is selected from a kind of of methyl alcohol, ethanol, propyl alcohol, Virahol, butanols or isopropylcarbinol.
5. a kind of L-citrulline-method of preparing malic acid as claimed in claim 1 is characterized in that: mixed solvent is sherwood oil, methyl alcohol: or normal hexane, ethanol: or sherwood oil, ethanol: or normal hexane, propyl alcohol: or sherwood oil, propyl alcohol: or normal hexane, Virahol: or sherwood oil, Virahol: or normal hexane, propyl carbinol: or sherwood oil, propyl carbinol: or normal hexane, isopropylcarbinol: or sherwood oil, isopropylcarbinol.
6. a kind of L-citrulline-method of preparing malic acid as claimed in claim 1 is characterized in that: crystallization comprised L-citrulline-L oxysuccinic acid 1: 1, L-citrulline-L oxysuccinic acid 2: 1, L-citrulline-DL oxysuccinic acid 1: 1, or L-citrulline-DL oxysuccinic acid 2: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610029943 CN101037400A (en) | 2006-08-11 | 2006-08-11 | Preparation method of L-Ornithine-Malic Acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610029943 CN101037400A (en) | 2006-08-11 | 2006-08-11 | Preparation method of L-Ornithine-Malic Acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101037400A true CN101037400A (en) | 2007-09-19 |
Family
ID=38888604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610029943 Pending CN101037400A (en) | 2006-08-11 | 2006-08-11 | Preparation method of L-Ornithine-Malic Acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101037400A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591264A (en) * | 2008-05-27 | 2009-12-02 | 上海汉飞生化科技有限公司 | A kind of preparation method of crystal L-glutamine alpha-ketoglutarate |
-
2006
- 2006-08-11 CN CN 200610029943 patent/CN101037400A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591264A (en) * | 2008-05-27 | 2009-12-02 | 上海汉飞生化科技有限公司 | A kind of preparation method of crystal L-glutamine alpha-ketoglutarate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101591271A (en) | A kind of preparation method of crystal L-arginine alpha-ketoglutarate | |
| CN103342746B (en) | Method for preparing stable insulin aspart crystal | |
| US9550878B2 (en) | Method for producing stabilized amorphous calcium carbonate | |
| EP1391426A1 (en) | Method for the preparation of a silicic acid comprising extrudate, said extrudate, its use and a pharmaceutical composition comprising the said extrudate | |
| CN105061636B (en) | A kind of preparation method of chitosan citrate rare earth compounding | |
| CN1319930C (en) | Preparation method of gluconic acid and its salt | |
| CN101659622A (en) | Method for splitting valine | |
| CN1319937C (en) | D-calcium pantothenate synthesis method | |
| CN101037400A (en) | Preparation method of L-Ornithine-Malic Acid | |
| CN101270074A (en) | Method for preparing high purity mitiglinide calcium | |
| CN101591257B (en) | Preparation method of crystal L-arginine L-aspartate | |
| CN101077863A (en) | Modified method for chemically synthesizing N-acetyl-L-carnosine | |
| CN101121672B (en) | Betaine phosphate and its producing method and applicaiton | |
| CN1476782A (en) | Preparation process of complete-component pearl product | |
| CN101659623A (en) | Method for resolving DL-Amino Acid | |
| CN101591270A (en) | A kind of preparation method of crystal type citrulline alpha-ketoglutarate | |
| CN1635128A (en) | Enzymatic conversion preparation method of γ-aminobutyric acid | |
| US20040133040A1 (en) | Creatine salts and method of making same | |
| CN1144533C (en) | Compound amino acid calcium salt calcium supplement and production method thereof | |
| CN1868451A (en) | Injection prepn. contg. cardxacin, and its prepn. method | |
| CN101591264A (en) | A kind of preparation method of crystal L-glutamine alpha-ketoglutarate | |
| CN1196392A (en) | Method for preparing levomethionine by decomposing mixed methionine with amino-acylation-hoydrolase | |
| CN109476578A (en) | Crystal of 3-hydroxyisovalerate amino acid salt and method for producing the same | |
| CN1176933C (en) | Magnesium zinc fructose diphosphate and its preparation method and application in pharmacy | |
| CN1712010A (en) | 5-Aminosalicylic acid intercalated drug sustained-release agent and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20070919 |