CN107522629A - A kind of preparation method of aspartic acid ornithine - Google Patents
A kind of preparation method of aspartic acid ornithine Download PDFInfo
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- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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Abstract
The present invention provides a kind of preparation method of aspartic acid ornithine, cationic ion-exchange resin is utilized by raw material of L ornithine hydrochlorides, by adsorbing, eluting, obtaining the free L ornithine aqueous solution except ammonia, the L ornithines aqueous solution with L asparatates by reacting, crystallize, it is refined after, dry after obtain finished product.The preparation method reaction condition of the present invention is simple, and cost is low, is adapted to industrialized production, obtained aspartic acid ornithine purity height and high income.
Description
Technical field
The present invention relates to pharmaceutical chemistry technical field, more particularly to a kind of preparation method of aspartic acid ornithine.
Background technology
The salt that aspartic acid ornithine is L-ASPARTIC ACID and L-Orn after chemical reaction is formed, chemical entitled (S)-
2,5- diaminovaleric acids-(S) -2- aminosuccinic acid salt, molecular formula C9H19N3O6, molecular weight 265.27, structural formula is：
Aspartic acid ornithine is that one kind treats liver disease drug, especially suitable for the central nervous system caused by liver disease
The releasing for symptom of uniting and the rescue of hepatic coma.
At present, the preparation method of aspartic acid ornithine mainly has following several method：
Patent DE4020980, EP0464325A3 and EP0464325B1 of German Degussa company, use arginase
L-arginine is converted into L-Orn, then reacts with ASPARTIC ACID to obtain aspartic acid ornithine again.This method makes
Arginase is expensive, and cost is higher, is unsuitable for industrialized production.
1967, the BP GB1067742 of Japanese KYOWA HAKKO KOGYO applications, using strong acidic ion
Exchanger resin dissociates L-ornithine hydrochloride, then obtains aspartic acid ornithine one into salt, crystallization with L-ASPARTIC ACID reaction
Hydrate, this method yield is extremely low and is crystallization water-bound.
The Chinese patent CN101100435A of Shanghai Yifurui Industry Co., Ltd's application, L-Orn sulfate is dissolved in
In water, add ASPARTIC ACID, add dissolving, with barium hydroxide and L-Orn sulfate in sulfuric acid, cold filtration,
Barium sulfate is removed, then the barium ions of residual is chelated with D403 chelating resins, chelating resin is filtered to remove, concentrates, decolourize, crystallize
To finished product.This method introduces the barium ions of severe toxicity, is unsuitable for industrialized production.
The Chinese patent CN102475697A of Xiong Guoyu applications, disclose a kind of with nanofiltration processing L-aminobutanedioic acid bird ammonia
Acid reaction liquid, desalination, concentration, recrystallization, obtain the method for aspartate for injection ornithine.The nanofiltration that this method uses
Condition is harsh, and cost is high, is not suitable for industrialized production.
The Chinese patent CN102964261A of the applications such as Xiao Wenhui, using electrodialysis methods, using charged ion in electric current
The lower mobile principle of effect removes the chlorion in ornithine hcl 99, is then made with L-ASPARTIC ACID into salt.This method
Weak point is electric dialyzator desalination harshness, and catholyte process produces inflammable and explosive hydrogen, is not suitable for industrialized production.
The Chinese patent CN103864634B of Changzhou Lanling Pharmaceutical Co., Ltd.'s application, by the L-ornithine hydrochloride aqueous solution
The L-Orn aqueous solution is obtained through 732 type storng-acid cation exchange resin desalting processings, adds ASPARTIC ACID reaction, rotation
Water is evaporated off, organic solvent crystallizes to obtain crude product, is refining to obtain finished product.This method is disadvantageous in that reaction needs to concentrate after terminating
Water removal, it is higher to equipment requirements such as shop equipment especially drawdown pumps, while artificial increased ammoniacal liquor can be in product in crystallization processes
It is middle to introduce excessive ammonium salt.
The Chinese patent CN101798275A of Chongqing Lybon Pharm -Tech Co., Ltd.'s application, ASPARTIC ACID is added
L-Orn acetate aqueous solution, pH value is adjusted to 6~9 with ammoniacal liquor, decolourizes, is recrystallized to give finished product.This method organic solvent
Dosage is big, and cost is of a relatively high；And the more difficult removing of ammonium acetate that generates after reacting, inevitably bring into crystalline product and
Influence the purity of product.
The content of the invention
It is an object of the invention to overcome drawbacks described above, there is provided a kind of purity height and the aspartic acid ornithine of high income
Preparation method, reaction condition is simple, and cost is low, be adapted to industrialized production.
In order to solve the above-mentioned technical problem, the technical solution adopted by the present invention is：
A kind of preparation method of aspartic acid ornithine, comprises the following steps,
Step 1：L-ornithine hydrochloride is mixed with water and dissolved, is subsequently added into the cation exchange tree after activation
Adsorbed in fat, the cationic ion-exchange resin is then first eluted with water, and (cation for being adsorbed with L-ornithine hydrochloride is handed over
Change resin) the not chloride ion-containing into leacheate, then carried out with ammoniacal liquor eluting to obtain eluent；
Step 2：Step 1 gained eluent be concentrated under reduced pressure and carries out removing ammonia, obtains free L-Orn feed liquid；
Step 3：The free L-Orn feed liquid of step 2 is mixed with ASPARTIC ACID and reacted, obtains L-aminobutanedioic acid
The aqueous solution of ornithine, the aqueous solution of aspartic acid ornithine is then heated to 40~80 DEG C, it is organic to add first
Solvent be incubated 1h, then crystallisation by cooling, filtering, obtain aspartic acid ornithine semifinished product, wherein the first organic solvent be methanol,
One or more in ethanol, isopropanol, acetone, propane diols；
Step 4：Add water to be dissolved to the aspartic acid ornithine semifinished product of step 3, be subsequently added into activated carbon and taken off
Color, then filter off except activated carbon, obtain filtrate, filtrate is heated to 40~80 DEG C, add the second organic solvent insulation 1h, so
Crystallisation by cooling, filtering and drying afterwards, aspartic acid ornithine finished product is obtained, wherein the second organic solvent is methanol, ethanol, isopropyl
One or more in alcohol, acetone, propane diols.
The beneficial effects of the present invention are：(1) the inventive method is effectively reduced in product without concentration water removal for a long time
The generation of impurity, and then the purity of product is improved, while reduce and concentrator is depended on unduly；(2) the inventive method
The step of simple, process stabilizing, reduce loss of the aspartic acid ornithine in each step, effectively increase the receipts of product
Rate, it is adapted to industrial production demand；(3) the inventive method has the advantages of reaction condition is simple, cost is low, easily operated.
Embodiment
To describe the technology contents of the present invention, construction feature, the objects and the effects in detail, below in conjunction with embodiment
It is explained in detail.
The design of most critical of the present invention is：Cationic ion-exchange resin is utilized by raw material of L-ornithine hydrochloride, is passed through
Absorption, elution, obtain the free L-Orn aqueous solution except ammonia, the L-Orn aqueous solution and ASPARTIC ACID by reaction,
Finished product is obtained after crystallization, refined rear, drying.
A kind of preparation method of aspartic acid ornithine, comprises the following steps,
Step 1：Step 1：L-ornithine hydrochloride is mixed with water and dissolved, is subsequently added into the cation after activation
Adsorbed in exchanger resin, the cationic ion-exchange resin is then first eluted with water and (is adsorbed with the sun of L-ornithine hydrochloride
Ion exchange resin) the not chloride ion-containing into leacheate, then carried out with ammoniacal liquor eluting to obtain eluent；
Step 2：Step 1 gained eluent be concentrated under reduced pressure and carries out removing ammonia, obtains free L-Orn feed liquid；
Step 3：The free L-Orn feed liquid of step 2 is mixed with ASPARTIC ACID and reacted, obtains L-aminobutanedioic acid
The aqueous solution of ornithine, the aqueous solution of aspartic acid ornithine is then heated to 40~80 DEG C, it is organic to add first
Solvent be incubated 1h, then crystallisation by cooling, filtering, obtain aspartic acid ornithine semifinished product, wherein the first organic solvent be methanol,
One or more in ethanol, isopropanol, acetone, propane diols；
Step 4：Add water to be dissolved to the aspartic acid ornithine semifinished product of step 3, be subsequently added into activated carbon and taken off
Color, then filter off except activated carbon, obtain filtrate, filtrate is heated to 40~80 DEG C, add the second organic solvent insulation 1h, so
Crystallisation by cooling, filtering and drying afterwards, aspartic acid ornithine finished product is obtained, wherein the second organic solvent is methanol, ethanol, isopropyl
One or more in alcohol, acetone, propane diols.
The present invention principle be：Chemical neutralization reaction is carried out between L-ASPARTIC ACID and L-Orn and prepares L-aminobutanedioic acid
Ornithine, in preparation process two important raw materials be L-ASPARTIC ACID and L-Orn mainly with nature in the presence of
Native compound purified and obtained, it is directly anti-with L-aminobutanedioic acid because L-Orn mainly exists with hydrochloride form
In requisition for addition acid binding agent, and final product quality can be caused to decline, coherent detection index such as chlorion, relevant material etc. are difficult to close
Lattice, need for ornithine hydrochloride to be prepared into free L-Orn for this.The invention provides a kind of ion exchange resin
Method, using cationic ion-exchange resin, by adsorbing, eluting, except ammonia obtains the free L-Orn aqueous solution, L-Orn water
Solution by reacting, crystallize, it is refined after, dry after obtain finished product, it is dense by the mass concentration scope control, the feed liquid that elute ammoniacal liquor
The limit handling of degree and wherein ammoniacal liquor, react pH scopes, crystallized mixed solvent ratios and crystallization temperature and crystallization temperature control
System etc. is further to improve the purity of product and yield.
It is involved in the present invention react chemical formula is as follows：
It was found from foregoing description, the beneficial effects of the present invention are：(1) the inventive method removes water without concentration for a long time,
Effectively reduce the generation of impurity in product, and then improve the purity of product, at the same reduce to concentrator it is excessive according to
Rely；(2) the step of the inventive method is simple, process stabilizing, reduces loss of the aspartic acid ornithine in each step, effectively
The yield of product is improved, is adapted to industrial production demand；(3) the inventive method has that reaction condition is simple, cost is low, is easy to
The advantages of operation.
Further, the mass concentration of ammoniacal liquor described in step 1 is 4~8%.
Seen from the above description, the mass concentration of ammoniacal liquor is too low, then elution effect is poor, consumes a large amount of eluents, subsequently
Crystallization needs to add the raising of recrystallisation solvent volume, and the yield of finished product declines and process costs improve, too high, elution effect enhancing,
But elution process heat release is obvious, while the free L-Orn concentration of gained is excessive, while greatly exacerbates impurity A (structure
Formula is as follows) generation, lmpurities A is higher, and final product quality declines obvious；
Further, the temperature used is concentrated under reduced pressure in step 2 as 30~80 DEG C.
Further, temperature is 40~60 DEG C used by being concentrated under reduced pressure in step 2.
Further, the concrete operations of the step 2 are：Step 1 gained eluent be concentrated under reduced pressure and carries out removing ammonia
Until the mass concentration of free ammonia is less than 0.25% in eluent, free L-Orn feed liquid is obtained.
Seen from the above description, the mass concentration for controlling free ammonia in eluent is less than 0.25%, avoids free ammonia mistake
Height causes to occur in product to be difficult to the ammonium salt removed and causes product unqualified.
Further, the dissociate L-Orn concentration of dissociating in L-Orn feed liquid of rate-determining steps 2 is 100~200mg/mL.
Seen from the above description, if the concentration of free L-Orn concentration is too low, later crystallization needs can be caused to add
The volume of recrystallisation solvent improves, and causes product yield to decline, and process costs improve, if the concentration mistake of free L-Orn concentration
Height, required concentration time is long, causes increasing for above-mentioned impurity A, meanwhile, increase equipment energy consumption, be unfavorable for industrialization.
Further, the concrete operations of step 3 are：The free L-Orn feed liquid of step 2 is mixed with ASPARTIC ACID
Close, and adjust the pH value of solution and reacted to 6~7, the aqueous solution of aspartic acid ornithine is obtained, then by L-aminobutanedioic acid bird ammonia
The aqueous solution of acid is heated to 55~75 DEG C, adds the first organic solvent insulation 1h, is subsequently cooled to 20~30 DEG C of progress
Crystallization, then filters, obtains aspartic acid ornithine semifinished product, wherein the first organic solvent is methanol, ethanol, isopropanol, third
One or more in ketone, propane diols.
Seen from the above description, the pH value of solution is adjusted 6~7, avoids the free bird for having neither part nor lot in reaction in product being present
Propylhomoserin or L-aminobutanedioic acid, the important indicator aspartic acid ornithine ratio of liquid phase HPLC monitoring is unqualified, causes final product quality not
It is qualified；Control heating-up temperature to promote the dissolvings of raw material for 55~75 DEG C and crystallize to improve product quality, avoid exceeding simultaneously
The boiling point of organic solvent causes bumping.
Further, first organic solvent and the second organic solvent are methanol.
Further, the weight of the dosage of second organic solvent and the dosage of water ratio is 2~4: 1 in step 4.
Seen from the above description, from methanol as first and second organic solvent, while the second organic solvent and water are controlled
Weight is than to take into account the yield and purity of product simultaneously.
Embodiment 1
Step 1：100gL- ornithine hydrochlorides are dissolved in 1000g water, the SK1B cations after 10kg is activated are handed over
After changing resin adsorption, SK1B cationic ion-exchange resins are washed with water to leacheate not chloride ion-containing, are then eluted with 5.0% ammoniacal liquor,
The eluent of pH >=9 is collected, stops collecting when controlling elution feed concentration 15mg/mL in HPLC, obtains eluent；
Step 2：The eluent of step 1 is concentrated under reduced pressure at 50 DEG C, and except ammonia, into eluent, the mass concentration of free ammonia is
0.1%, obtain free L-Orn feed liquid, concentration 175mg/mL；
Step 3：At room temperature, ASPARTIC ACID (2.5 is slowly added portionwise into the free L-Orn feed liquid of step 2
~2.6g/min) mixed, and the pH value for adjusting solution is 6.5, (is started to having reacted from addition ASPARTIC ACID, greatly
About 30min, pH value judge that reaction is complete for no longer fluctuation), 70 DEG C are heated to, is slow added into the insulation of 956g methanol
1h, then slowly it is cooled to 25 DEG C and is crystallized and then filtered, obtain crude white solid (aspartic acid ornithine semifinished product)
138g；
Step 4：It is complete that step 3 gained aspartic acid ornithine semifinished product is added to 345g water dissolving, 2.5g is added and lives
Property carbon decoloring 0.5h, then filter off except activated carbon, obtain filtrate, filtrate is heated to 70 DEG C, add 821g methanol insulation
1h, then slowly it is cooled to 25 DEG C of crystallizations, filters to obtain filter cake, filter cake is dried in vacuo under 45 DEG C of environment, obtains L-aminobutanedioic acid bird
Propylhomoserin finished product 121g, the purity of aspartic acid ornithine finished product is 99.7%, aspartic acid ornithine ratio 2.77, product yield
For 76.9%.
Wherein product yield is molar yield, and calculation is as follows：
Product yield (%)={ WFinished product/[(WL-ornithine hydrochloride/ 168.62) × 265.27] } × 100%
Symbol description：
WFinished product--- the weight (g) of product；WL-ornithine hydrochloride--- the weight (g) for the L-ornithine hydrochloride that feeds intake；
168.62 --- the molal weight of ornithine hydrochloride；265.27 --- finished product is mole of aspartic acid ornithine
Quality.
Embodiment 2
Step 1：100gL- ornithine hydrochlorides are dissolved in 1000g water, the SK1B cations after 10kg is activated are handed over
After changing resin adsorption, SK1B cationic ion-exchange resins are washed with water to leacheate not chloride ion-containing, are then eluted with 5.0% ammoniacal liquor,
The eluent of pH >=9 is collected, stops collecting when controlling elution feed concentration 15mg/mL in HPLC, obtains eluent；
Step 2：The eluent of step 1 is concentrated under reduced pressure at 50 DEG C, and except ammonia, into eluent, the mass concentration of free ammonia is
0.2%, obtain free L-Orn feed liquid, concentration 164mg/mL；
Step 3：At room temperature, ASPARTIC ACID progress is slowly added portionwise into the free L-Orn feed liquid of step 2
Mixing, and the pH value for adjusting solution is 6.9, to having reacted, is heated to 70 DEG C, is slow added into 1018g methanol insulation 1h,
Then slowly it is cooled to 25 DEG C and is crystallized and then filtered, obtains crude white solid (aspartic acid ornithine semifinished product) 129g；
Step 4：It is complete that step 3 gained aspartic acid ornithine semifinished product is added to 323g water dissolving, 2.5g is added and lives
Property carbon decoloring 0.5h, then filter off except activated carbon, obtain filtrate, filtrate is heated to 70 DEG C, add 768g methanol insulation
1h, then slowly it is cooled to 25 DEG C of crystallizations, filters to obtain filter cake, filter cake is dried in vacuo under 45 DEG C of environment, obtains L-aminobutanedioic acid bird
Propylhomoserin finished product 119g, the purity of aspartic acid ornithine finished product is 99.8%, aspartic acid ornithine ratio 2.81, product yield
For 75.6% (computational methods are with embodiment 1).
Embodiment 3
Step 1：100gL- ornithine hydrochlorides are dissolved in 1000g water, the JK006 gel-types sun after 10kg is activated
After ion exchange resin absorption, JK006 gel-network precipitation methods (being adsorbed with ornithine hydrochloride) are washed with water to elution
Liquid not chloride ion-containing, then eluted with 5.0% ammoniacal liquor, collect the eluent of pH >=9, control elution feed concentration 15mg/ in HPLC
Stop collecting during mL, obtain eluent；
Step 2：The eluent of step 1 is concentrated under reduced pressure at 50 DEG C, and except ammonia, into eluent, the mass concentration of free ammonia is
0.1%, obtain free L-Orn feed liquid, concentration 185mg/mL；
Step 3：At room temperature, ASPARTIC ACID progress is slowly added portionwise into the free L-Orn feed liquid of step 2
Mixing, and the pH value for adjusting solution is 6.5, to having reacted, is heated to 70 DEG C, is slow added into 867g methanol insulation 1h,
Then slowly it is cooled to 25 DEG C and is crystallized and then filtered, obtains crude white solid (aspartic acid ornithine semifinished product) 136g；
Step 4：It is complete that step 3 gained aspartic acid ornithine semifinished product is added to 340g water dissolving, 2.5g is added and lives
Property carbon decoloring 0.5h, then filter off except activated carbon, obtain filtrate, filtrate is heated to 70 DEG C, add 809g methanol insulation
1h, then slowly it is cooled to 25 DEG C of crystallizations, filters to obtain filter cake, filter cake is dried in vacuo under 45 DEG C of environment, obtains L-aminobutanedioic acid bird
Propylhomoserin finished product 120g, the purity of aspartic acid ornithine finished product is 99.5%, aspartic acid ornithine ratio 2.79, product yield
For 76.3% (computational methods are with embodiment 1).
Embodiment 4
Step 1：100g ornithine hydrochlorides are dissolved in 1000g water, the SK1B gel-types sun after 10kg is activated from
After sub-exchange resin absorption, SK1B gel-network precipitation methods (being adsorbed with ornithine hydrochloride) are washed with water to leacheate not
Chloride ion-containing, then eluted with 5.0% ammoniacal liquor, the eluent of pH >=9 is collected, when elution feed concentration 15mg/mL is controlled in HPLC
Stop collecting, obtain eluent；
Step 2：The eluent of step 1 is concentrated under reduced pressure at 50 DEG C, and except ammonia, into eluent, the mass concentration of free ammonia is
0.1%, obtain free L-Orn feed liquid, concentration 159mg/mL；
Step 3：At room temperature, ASPARTIC ACID progress is slowly added portionwise into the free L-Orn feed liquid of step 2
Mixing, and the pH value for adjusting solution is 6.0, to having reacted, is heated to 70 DEG C, is slow added into 1123g methanol insulation 1h,
Then slowly it is cooled to 25 DEG C and is crystallized and then filtered, obtains crude white solid (aspartic acid ornithine semifinished product) 142g；
Step 4：It is complete that step 3 gained aspartic acid ornithine semifinished product is added to 355g water dissolving, 2.5g is added and lives
Property carbon decoloring 0.5h, then filter off except activated carbon, obtain filtrate, filtrate is heated to 70 DEG C, add 845g methanol insulation
1h, then slowly it is cooled to 25 DEG C of crystallizations, filters to obtain filter cake, filter cake is dried in vacuo under 45 DEG C of environment, obtains L-aminobutanedioic acid bird
Propylhomoserin finished product 123g, the purity of aspartic acid ornithine finished product is 99.6%, aspartic acid ornithine ratio 2.92, product yield
For 78.2% (computational methods are with embodiment 1).
In summary, the preparation method of aspartic acid ornithine provided by the invention, removed water without long-time concentration, effectively
The generation of impurity in product is reduced, and then improves the purity of product, while reduces and concentrator is depended on unduly；This
The step of inventive method, is simple, process stabilizing, reduces loss of the aspartic acid ornithine in each step, effectively increases production
The yield of product, it is adapted to industrial production demand；The inventive method has the advantages of reaction condition is simple, cost is low, easily operated.
Embodiments of the invention are the foregoing is only, are not intended to limit the scope of the invention, it is every to utilize this hair
The equivalent structure or equivalent flow conversion that bright description is made, or directly or indirectly it is used in other related technology necks
Domain, it is included within the scope of the present invention.
Claims (8)
- A kind of 1. preparation method of aspartic acid ornithine, it is characterised in that comprise the following steps,Step 1：L-ornithine hydrochloride is mixed with water and dissolved, is subsequently added into cationic ion-exchange resin and is inhaled It is attached, cationic ion-exchange resin not chloride ion-containing into leacheate is first eluted with water, then carried out with ammoniacal liquor eluting to obtain eluent；Step 2：Step 1 gained eluent be concentrated under reduced pressure and carries out removing ammonia, obtains free L-Orn feed liquid；Step 3：The free L-Orn feed liquid of step 2 is mixed with ASPARTIC ACID and reacted, obtains L-aminobutanedioic acid bird ammonia The aqueous solution of acid, is then heated to 40~80 DEG C by the aqueous solution of aspartic acid ornithine, adds the first organic solvent 1h is incubated, then crystallisation by cooling, filtering, obtain aspartic acid ornithine semifinished product, wherein the first organic solvent is methanol, second One or more in alcohol, isopropanol, acetone, propane diols；Step 4：Add water to be dissolved to the aspartic acid ornithine semifinished product of step 3, be subsequently added into activated carbon and decolourized, so After filter off except activated carbon, obtain filtrate, filtrate be heated to 40~80 DEG C, add the second organic solvent insulation 1h, Ran Houleng But crystallize, filter and dry, obtain aspartic acid ornithine finished product, wherein the second organic solvent be methanol, ethanol, isopropanol, One or more in acetone, propane diols.
- 2. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that ammoniacal liquor described in step 1 Mass concentration be 4~8%.
- 3. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that be concentrated under reduced pressure in step 2 The temperature used is 30~80 DEG C.
- 4. the preparation method of aspartic acid ornithine according to claim 3, it is characterised in that be concentrated under reduced pressure in step 2 Used temperature is 40~60 DEG C.
- 5. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that the step 2 it is specific Operate and be：Step 1 gained eluent be concentrated under reduced pressure and carried out except ammonia until the mass concentration of free ammonia is in eluent Less than 0.25%, obtain free L-Orn feed liquid.
- 6. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that the concrete operations of step 3 For：The free L-Orn feed liquid of step 2 is mixed with ASPARTIC ACID, and the pH value for adjusting solution is anti-to 6~7 progress Should, the aqueous solution of aspartic acid ornithine is obtained, the aqueous solution of aspartic acid ornithine is then heated to 55~75 DEG C, then The first organic solvent insulation 1h is added, 20~30 DEG C is subsequently cooled to and is crystallized, then filter, obtain aspartic acid ornithine Semifinished product, wherein the first organic solvent is the one or more in methanol, ethanol, isopropanol, acetone, propane diols.
- 7. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that first organic solvent It is methanol with the second organic solvent.
- 8. the preparation method of aspartic acid ornithine according to claim 1, it is characterised in that second is organic in step 4 The weight of the dosage of solvent and the dosage of water ratio is 2~4: 1.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108840805A (en) * | 2018-08-03 | 2018-11-20 | 安徽省金楠医疗科技有限公司 | Aspartic acid ornithine synthetic method |
| CN110317144A (en) * | 2018-03-28 | 2019-10-11 | 上海贵之言医药科技有限公司 | A kind of aspartic acid ornithine Crystal form of double salt compound and preparation method thereof |
| CN114349652A (en) * | 2021-12-10 | 2022-04-15 | 汕头市佳禾生物科技有限公司 | Preparation method of L-lysine aspartate |
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| CN114349652A (en) * | 2021-12-10 | 2022-04-15 | 汕头市佳禾生物科技有限公司 | Preparation method of L-lysine aspartate |
| CN114349652B (en) * | 2021-12-10 | 2024-03-29 | 汕头市佳禾生物科技有限公司 | Preparation method of L-lysine aspartate |
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