CN113769794B - Ion exchange system and method for continuously removing impurities in citicoline sodium - Google Patents
Ion exchange system and method for continuously removing impurities in citicoline sodium Download PDFInfo
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- CN113769794B CN113769794B CN202110763689.3A CN202110763689A CN113769794B CN 113769794 B CN113769794 B CN 113769794B CN 202110763689 A CN202110763689 A CN 202110763689A CN 113769794 B CN113769794 B CN 113769794B
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- YWAFNFGRBBBSPD-OCMLZEEQSA-M sodium;[[(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound [Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 YWAFNFGRBBBSPD-OCMLZEEQSA-M 0.000 title claims abstract description 41
- 239000012535 impurity Substances 0.000 title claims abstract description 37
- 229960004774 citicoline sodium Drugs 0.000 title claims abstract description 35
- 238000005342 ion exchange Methods 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 26
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 161
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 161
- 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 abstract description 158
- 239000003513 alkali Substances 0.000 claims abstract description 94
- 238000005406 washing Methods 0.000 claims abstract description 79
- 239000002253 acid Substances 0.000 claims abstract description 71
- 230000008929 regeneration Effects 0.000 claims abstract description 66
- 238000011069 regeneration method Methods 0.000 claims abstract description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 60
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 239000007788 liquid Substances 0.000 claims abstract description 33
- 238000000926 separation method Methods 0.000 claims abstract description 27
- 238000010828 elution Methods 0.000 claims abstract description 24
- 239000003480 eluent Substances 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 66
- 239000010865 sewage Substances 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 30
- 239000011347 resin Substances 0.000 claims description 24
- 229920005989 resin Polymers 0.000 claims description 24
- 239000002994 raw material Substances 0.000 claims description 21
- 239000002699 waste material Substances 0.000 claims description 20
- 239000012267 brine Substances 0.000 claims description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 14
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 11
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 11
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 238000001179 sorption measurement Methods 0.000 claims description 11
- 238000011084 recovery Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 8
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 claims description 7
- 239000012527 feed solution Substances 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 239000002351 wastewater Substances 0.000 claims description 4
- 238000004065 wastewater treatment Methods 0.000 claims description 4
- 239000003957 anion exchange resin Substances 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 238000011010 flushing procedure Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 abstract description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 229960001284 citicoline Drugs 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 238000003860 storage Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229930183912 Cytidylic acid Natural products 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 description 1
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J47/00—Ion-exchange processes in general; Apparatus therefor
- B01J47/02—Column or bed processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J49/00—Regeneration or reactivation of ion-exchangers; Apparatus therefor
- B01J49/50—Regeneration or reactivation of ion-exchangers; Apparatus therefor characterised by the regeneration reagents
- B01J49/57—Regeneration or reactivation of ion-exchangers; Apparatus therefor characterised by the regeneration reagents for anionic exchangers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J49/00—Regeneration or reactivation of ion-exchangers; Apparatus therefor
- B01J49/80—Automatic regeneration
- B01J49/85—Controlling or regulating devices therefor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Treatment Of Water By Ion Exchange (AREA)
Abstract
The invention discloses an ion exchange system and a method for continuously removing impurities in citicoline sodium, which mainly solve the problems of low extraction yield and low purity of discharged products in the prior art. The system comprises a continuous ion exchange resin column unit, wherein the ion exchange resin column unit comprises a plurality of ion exchange resin columns capable of moving sequentially and circularly, the ion exchange resin column unit comprises a separation area, an elution area, a washing alcohol alkali area, a salt regeneration area, a washing salt area, an acid regeneration area, a washing acid area, an alkali regeneration area and a washing alkali area, the plurality of ion exchange resin columns sequentially move sequentially and circularly in the separation area, the elution area, the washing alcohol alkali area, the salt regeneration area, the washing salt area, the acid regeneration area, the washing acid area, the alkali regeneration area and the washing alkali area, the reasonable configuration ensures the purity of discharged products, the purity of citicoline sodium of separation liquid and eluent reaches 99.8%, and the extraction yield is more than or equal to 96%.
Description
Technical Field
The invention belongs to the technical field of biochemical separation, and particularly relates to an ion exchange system and method for continuously removing impurities in citicoline sodium.
Background
Sodium citicoline, also known as sodium citicoline, is a brain metabolism activator, which is a nucleoside derivative, a precursor of phosphatidylcholine, and also a coenzyme necessary for lecithin synthesis. Research shows that citicoline sodium has the functions of repairing brain injury, resisting oxidation, improving memory and enhancing intelligence, and has wide clinical application.
At present, the common chemical synthesis method is used for producing citicoline sodium, a fixed bed ion exchange process is adopted for feed liquid after synthesis, the manual operation error is large, and the yield is about 85%. The fixed bed process resin has a service cycle of 30 days, the flow rate of the upper column is 0.025BV, the material storage time is long, and 20% ethanol is selected for bacteriostasis in order to prevent bacteria from breeding and prevent the addition of ions to increase the conductivity. As the column is put on, citicoline sodium is degraded to produce derivative impurities, resulting in further reduction of the yield.
Therefore, the technical problems of low extraction yield and low purity of discharged products in the prior art need to be solved.
Disclosure of Invention
The invention aims to provide an ion exchange system and method for continuously removing impurities in citicoline sodium, which have high extraction yield and high purity of discharged products.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
an ion exchange system for continuously removing impurities in citicoline sodium; the ion exchange resin column unit comprises a plurality of ion exchange resin columns capable of moving sequentially and circularly, the ion exchange resin column unit comprises a separation zone, an elution zone, a washing alcohol alkali zone, a salt regeneration zone, a washing salt zone, an acid regeneration zone, a washing acid zone, an alkali regeneration zone and a washing alkali zone, and the plurality of ion exchange resin columns sequentially move sequentially and circularly in the separation zone, the elution zone, the washing alcohol alkali zone, the salt regeneration zone, the washing salt zone, the acid regeneration zone, the washing acid zone, the alkali regeneration zone and the washing alkali zone.
Further, the device also comprises a raw material liquid tank, a product tank, an alcohol alkali tank, an elution tank, a pure water tank, an alcohol recovery tank, a brine tank, a waste salt tank, a dilute acid tank and a dilute alkali tank; the total number of the ion exchange resin columns is 30, and the number is 1# -30;
the separation zone is provided with 6 ion exchange resin columns 25# -30#, a feed inlet of the 25# -30# ion exchange resin columns is communicated with the raw material liquid tank, and a discharge outlet of the 25# -30# ion exchange resin columns is communicated with the product tank and the sewage disposal channel;
the elution zone is provided with 3 ion exchange resin columns 22# -24# -connected in series, a feed inlet of the 22# -24# ion exchange resin columns is communicated with the alcohol alkali tank, and a discharge outlet of the 22# -24# ion exchange resin columns is communicated with the elution tank;
the washing alcohol alkali zone is provided with 3 ion exchange resin columns 19# -21# -connected in series, a feed inlet of the 19# -21# ion exchange resin columns is communicated with the pure water tank, and a discharge outlet of the 19# -21# ion exchange resin columns is respectively communicated with a sewage treatment channel and the alcohol recovery tank;
the salt regeneration zone is provided with 3 ion exchange resin columns 16# -18# -connected in series, a feed inlet of the 16# -18# ion exchange resin columns is communicated with the salt water tank, and a discharge outlet of the 16# -18# ion exchange resin columns is respectively communicated with the waste salt water tank and the sewage treatment channel;
the salt washing area is provided with 3 ion exchange resin columns 13# -15# -connected in series, a feed inlet of the 13# -15# ion exchange resin columns is communicated with the pure water tank, and a discharge outlet of the 13# -15# ion exchange resin columns is communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# -connected in series, a feed inlet of the 10# -12# ion exchange resin columns is communicated with a dilute acid tank, and a discharge outlet of the 10# -12# ion exchange resin columns is communicated with a waste acid and sewage treatment channel;
the acid washing area is provided with 3 ion exchange resin columns 7# -9# -connected in series, a feed inlet of the 7# -9 ion exchange resin columns is communicated with the pure water tank, and a discharge outlet of the 7# -9 ion exchange resin columns is communicated with the 10# -ion exchange resin columns;
the alkali regeneration zone is provided with 3 ion exchange resin columns 4# -6# -connected in series, a feed inlet of the 4# -6 ion exchange resin columns is communicated with a dilute alkali tank, and a discharge outlet of the 4# -6 ion exchange resin columns is communicated with a waste alkali sewage treatment channel;
the alkali washing zone is provided with 3 ion exchange resin columns 1# -3# -connected in series, a feed inlet of the 1# -3 ion exchange resin columns is communicated with the pure water tank, and a discharge outlet of the 1# -3 ion exchange resin columns is communicated with the 4# ion exchange resin columns.
Further, the ion exchange resin column washing device also comprises 4 pure water pumps, wherein the feed inlets of the pure water pumps are communicated with the pure water tank, and the discharge outlets of the 4 pure water pumps are respectively communicated with the 1# ion exchange resin column, the 7# ion exchange resin column, the 13# ion exchange resin column and the 19# ion exchange resin column in a one-to-one correspondence mode so as to top wash the ion exchange resin column.
Further, the dilute alkali tank is filled with 1mol/L NaOH solution, the dilute acid tank is filled with 1mol/L HCl solution, and the brine tank is filled with 4% NaCl solution by mass.
Further, the alcohol alkali tank is filled with a mixed solution of NaOH solution and ethanol solution, and the preparation method of the mixed solution comprises the following steps: preparing NaOH solution with the concentration of 1mol/L in ethanol water solution with the volume concentration of 20%; the raw material liquid in the raw material liquid tank contains citicoline sodium and impurities, and the impurities contain cytidine acid.
Further, the plurality of ion exchange resin columns are each an anion exchange resin column.
The invention also provides an ion exchange method for continuously removing impurities in citicoline sodium, which comprises the following steps:
(1) The method comprises the steps that raw material liquid containing citicoline sodium and impurities enters a continuous ion exchange system, and separation liquid is obtained through adsorption separation in sequence by an ion exchange resin column unit; eluting with alcohol alkali solution to obtain eluent;
(2) The resin column adsorbed and eluted in the step (1) is sequentially subjected to water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment, and the operation is circulated again.
Further, the continuous ion exchange system comprises 30 ion exchange resin columns with the number of 1# -30, and the process of separating the separation liquid by adsorption in the step (1) is as follows:
the raw material liquid is parallelly connected into 25# +27# and 26# +28# ion exchange resin columns through a conveying pump, then serially connected into 29# +30# ion exchange resin columns, and the separated liquid from the 30# ion exchange resin columns is sectionally fed into a product tank and a sewage disposal channel respectively.
Further, the raw material liquid contains citicoline sodium and impurities, the impurities contain cytidine acid, and the adsorption force of the 30 ion exchange resin columns on the cytidine acid is larger than that of the citicoline sodium.
Further, the service cycle of the ion exchange resin column is 3h, and the flow rate of the upper column is 1.5-2BV.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention provides a continuous ion exchange system for producing citicoline sodium, which comprises a continuous ion exchange resin column unit, wherein the ion exchange resin column unit comprises a plurality of ion exchange resin columns which can move sequentially and circularly run, the ion exchange resin column unit comprises a separation area, an elution area, a washing alcohol alkali area, a salt regeneration area, a washing salt area, an acid regeneration area, a washing acid area, an alkali regeneration area and a washing alkali area, the plurality of ion exchange resin columns sequentially move sequentially and circularly run in the separation area, the elution area, the washing alcohol alkali area, the salt regeneration area, the washing salt area, the acid regeneration area, the washing acid area, the alkali regeneration area and the washing alkali area, the reasonable configuration ensures the purity of discharged products, the purity of citicoline sodium of separating liquid and eluent reaches 99.8%, and the extraction yield is more than or equal to 96%;
(2) The service cycle of the ion exchange system resin provided by the invention is 3 hours, the flow rate of the upper column is 1.5-2BV, the treatment speed is high, the material storage time is short, ethanol is not required to be added for bacteriostasis, and the addition of raw material liquid ethanol is avoided;
(3) The method reduces the consumption of regenerated acid and alkali through the control of the flow, reduces the cost and is more environment-friendly;
(4) The invention realizes whole-course automatic and continuous production through the continuous ion exchange system, and improves the efficiency.
Drawings
FIG. 1 is a schematic diagram of an ion exchange system for continuously removing sodium citicoline impurity in the present invention.
Reference numerals:
11. ion exchange resin column, 12, raw material liquid tank, 13, product tank, 14, alcohol alkali tank, 15, eluting tank, 16, pure water tank, 17, alcohol recovery tank, 18, brine tank, 19, waste salt tank, 20, dilute acid tank, 21, dilute alkali tank.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Referring to fig. 1, the invention provides an ion exchange system for continuously removing impurities in citicoline sodium, which comprises a continuous ion exchange resin column unit, wherein the ion exchange resin column unit comprises a plurality of ion exchange resin columns 11 which can move sequentially and circularly, the ion exchange resin column unit comprises a separation zone, an elution zone, a washing alcohol alkali zone, a salt regeneration zone, a washing salt zone, an acid regeneration zone, a washing acid zone, an alkali regeneration zone and a washing alkali zone, and the plurality of ion exchange resin columns 11 sequentially move sequentially and circularly in the separation zone, the elution zone, the washing alcohol alkali zone, the salt regeneration zone, the washing salt zone, the acid regeneration zone, the washing acid zone, the alkali regeneration zone and the washing alkali zone.
Referring to fig. 1, the ion exchange system for continuously removing impurities in citicoline sodium provided in this embodiment further includes a raw material liquid tank 12, a product tank 13, an alcohol alkali tank 14, an elution tank 15, a pure water tank 16, an alcohol recovery tank 17, a brine tank 18, a waste salt tank 19, a dilute acid tank 20 and a dilute alkali tank 21; the total number of the ion exchange resin columns 11 is 30, and the number is 1# -30#;
the separation zone is provided with 6 ion exchange resin columns 25# -30#, a feed inlet of the 25# -30# ion exchange resin columns is communicated with the raw material liquid tank 12, and a discharge outlet of the 25# -30# ion exchange resin columns is communicated with the product tank 13 and the sewage disposal channel;
the elution zone is provided with 3 ion exchange resin columns 22# -24# -connected in series, wherein a feed inlet of the 22# -24# ion exchange resin columns is communicated with an alcohol alkali tank 14, and a discharge outlet of the 22# -24# ion exchange resin columns is communicated with an elution tank 15;
the washing alcohol alkali zone is provided with 3 ion exchange resin columns 19# -21# -connected in series, a feed inlet of the 19# -21# ion exchange resin columns is communicated with a pure water tank 16, and a discharge outlet of the 19# -21# ion exchange resin columns is respectively communicated with a sewage treatment channel and an alcohol recovery tank 17;
the salt regeneration zone is provided with 3 ion exchange resin columns 16# -18# -connected in series, a feed inlet of the 16# -18# ion exchange resin columns is communicated with a brine tank 18, and a discharge outlet of the 16# -18# ion exchange resin columns is respectively communicated with a waste salt tank 19 and a sewage treatment channel;
the salt washing area is provided with 3 ion exchange resin columns 13# -15# -connected in series, a feed inlet of the 13# -15# ion exchange resin columns is communicated with a pure water tank 16, and a discharge outlet of the 13# -15# ion exchange resin columns is communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# -connected in series, a feed inlet of the 10# -12# ion exchange resin columns is communicated with a dilute acid tank 20, and a discharge outlet of the 10# -12# ion exchange resin columns is communicated with a waste acid and sewage treatment channel;
the acid washing area is provided with 3 ion exchange resin columns 7# -9# -connected in series, a feed inlet of the 7# -9 ion exchange resin columns is communicated with a pure water tank 16, and a discharge outlet of the 7# -9 ion exchange resin columns is communicated with a 10# -ion exchange resin column;
the alkali regeneration zone is provided with 3 ion exchange resin columns 4# -6# -connected in series, a feed inlet of the 4# -6 ion exchange resin columns is communicated with a dilute alkali tank 21, and a discharge outlet of the 4# -6 ion exchange resin columns is communicated with a waste alkali sewage treatment channel;
the alkali washing zone is provided with 3 ion exchange resin columns 1# -3# -connected in series, a feed inlet of the 1# -3 ion exchange resin columns is communicated with a pure water tank 16, and a discharge outlet of the 1# -3 ion exchange resin columns is communicated with a 4# -ion exchange resin column.
The embodiment further comprises 4 pure water pumps (not labeled in fig. 1), wherein the feed inlets of the pure water pumps are communicated with the pure water tank 16, and the discharge outlets of the 4 pure water pumps are respectively communicated with the 1# ion exchange resin column, the 7# ion exchange resin column, the 13# ion exchange resin column and the 19# ion exchange resin column in a one-to-one correspondence manner so as to top wash the ion exchange resin columns.
The embodiment further comprises a connecting pipeline, an automatic control valve and an automatic control system, wherein the connecting pipeline is used for communicating the tank bodies with the ion exchange resin column 11, communicating a sewage treatment channel with the ion exchange resin column 11 and the like, and the automatic control system periodically controls each/every group of ion exchange columns through the automatic control valve to realize the processes of separation, elution, salt regeneration, acid regeneration, alkali regeneration and water ejection. The automatic control system of the invention controls the ion exchange columns of each group periodically through the automatic control valve to realize the processes of separation, elution, salt regeneration, acid regeneration, alkali regeneration and water ejection, and the purity of discharged products is ensured by reasonable configuration. The whole-process automatic and continuous production is realized through the continuous ion exchange system, and the efficiency is improved.
In the embodiment, the dilute alkali tank 21 is filled with 1mol/L NaOH solution, the dilute acid tank 20 is filled with 1mol/L HCl solution, and the brine tank 18 is filled with 4% NaCl solution by mass; the alcohol alkali tank 14 contains a mixed solution of ethanol solution and NaOH, and the preparation method of the mixed solution comprises the following steps: preparing NaOH solution with the final concentration of 1mol/L in ethanol water solution with the volume concentration of 20%; the feed solution in the feed solution tank 12 contains sodium citicoline and impurities including cytidine acid and an impurity D of an unknown composition.
Through liquid chromatography test, liquid chromatography peak of citicoline sodium appears at 4.5min, impurity cytidylic acid peak appears at about 7min, and impurity D with unknown composition appears at about 24.5 min. The ion exchange resin column used in the invention has the weakest adsorption capacity to citicoline sodium, and can be eluted by using alcohol-alkali mixed solution (namely the mixed solution of the ethanol solution and the NaOH solution); the adsorption capacity for impurity D is inferior, and the adsorption capacity for impurity B is strongest.
The ion-exchange resin columns used in this example were each obtained by packing (85% of the resin column volume in terms of loading) with an anion-exchange resin produced by Shandong Zibo Co., ltd. The service cycle of the ion exchange resin column is 3h, and the flow rate of the upper column is 1.5-2BV
The process of separating the product and regenerating the resin by the ion exchange system for continuously removing the impurities in the citicoline sodium provided by the embodiment is as follows, namely, the ion exchange method for continuously removing the impurities in the citicoline sodium comprises the following steps:
(1) The method comprises the steps that raw material liquid containing citicoline sodium and impurities enters a continuous ion exchange system, and separation liquid is obtained through adsorption separation in sequence by an ion exchange resin column unit; eluting with alcohol alkali solution to obtain eluent;
(2) The resin column adsorbed and eluted in the step (1) is sequentially subjected to water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment, and the operation is circulated again.
Specifically, in the above steps:
isolation (25-30 #): the raw material liquid is connected in parallel through a conveying pump and enters a 25# +27#/26# +28# resin column, then is connected in series into a 29# +30# resin column, the separated liquid from the 30# resin column is collected in sections, one section of the separated liquid is free of content and enters a sewage discharge pipeline, the other section of the separated liquid is up to the standard in purity, and the separated liquid enters a product tank;
elution (22-24 #): after resin adsorption saturation, eluting, wherein an alcohol-alkali tank provides an eluting raw solution, three resin columns are connected in series, and the eluting solution enters an eluting tank;
washing the alcohol base (19-21 #): the pure water cleans the materials in the resin column, one part (section (1)) of the materials with high ethanol alkali content enters an alcohol recovery tank, and the other part (section (2)) enters a sewage treatment channel to lead to a sewage treatment working section;
salt regeneration (16-18 #): brine is serially connected into a 16# +17# +18# resin column, adsorbed cytidine acid impurity and impurity D are eluted, the adsorbed cytidine acid impurity and impurity D enter a sewage treatment channel to be led to a sewage treatment working section, and waste brine enters a waste brine tank;
washing salt (13-15 #): the pure water cleans the materials in the resin column, and flushing water enters a sewage treatment channel to be led to a sewage treatment working section;
acid regeneration (10-12 #): three resin columns are connected in series, and wastewater enters a waste acid and sewage treatment channel to be led to a sewage treatment working section;
washing with water acid (7-9 #): washing the acid in the resin column by pure water, and allowing the effluent and the dilute acid tank feed solution to enter a resin column 10#;
alkali regeneration (4-6 #): three resin columns are connected in series, and wastewater enters a waste alkali wastewater treatment channel to be led to a wastewater treatment working section;
washing with water base (1-3 #): and (3) washing the alkali in the resin column by pure water, and allowing the effluent and the dilute alkali tank feed solution to enter the resin column 4#.
The above system and method were used to process 3 different batches of raw materials, and the results of the sodium citicoline content, purity and yield of the discharged materials are shown in table 1.
TABLE 1 discharge of sodium citicoline treated by the invention
As can be seen from Table 1, after separation by the technical scheme provided by the invention, the purity of the product is improved to more than 99.8%, and the yield is more than 96%.
The service cycle of the ion exchange system resin provided by the invention is 3 hours, the flow rate of the upper column is 1.5-2BV, the treatment speed is high, the material storage time is short, ethanol is not required to be added for bacteriostasis, and the addition of raw material liquid ethanol is avoided; the method reduces the consumption of regenerated acid and alkali, reduces the cost and is more environment-friendly through the control of the flow.
The above-mentioned embodiments are only preferred embodiments of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention should be covered by the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims (7)
1. An ion exchange system for continuously removing impurities in citicoline sodium, which is characterized in that: the ion exchange resin column unit comprises a plurality of ion exchange resin columns which can move sequentially and circularly, wherein the ion exchange resin column unit comprises a separation zone, an elution zone, a washing alcohol-alkali zone, a salt regeneration zone, a washing salt zone, an acid regeneration zone, a washing acid zone, an alkali regeneration zone and a washing alkali zone, and the plurality of ion exchange resin columns sequentially move and circularly in the separation zone, the elution zone, the washing alcohol-alkali zone, the salt regeneration zone, the washing salt zone, the acid regeneration zone, the washing acid zone, the alkali regeneration zone and the washing alkali zone;
the device also comprises a raw material liquid tank, a product tank, an alcohol alkali tank, an elution tank, a pure water tank, an alcohol recovery tank, a brine tank, a waste salt tank, a dilute acid tank and a dilute alkali tank; the total number of the ion exchange resin columns is 30, and the number is 1# -30;
the separation zone is provided with 6 ion exchange resin columns 25# -30#, a feed inlet of the ion exchange resin columns 25# -30# is communicated with the raw material liquid tank, and a discharge outlet of the ion exchange resin columns 25# -30# is communicated with the product tank and the sewage disposal channel;
the elution zone is provided with 3 ion exchange resin columns 22# -24# -connected in series, a feed inlet of the ion exchange resin column 22# -24# is communicated with the alcohol alkali tank, and a discharge outlet of the ion exchange resin column 22# -24# is communicated with the elution tank;
the washing alcohol alkali zone is provided with 3 ion exchange resin columns 19# -21# -connected in series, a feed inlet of the ion exchange resin columns 19# -21# is communicated with the pure water tank, and a discharge outlet of the ion exchange resin columns 19# -21# is respectively communicated with a sewage treatment channel and the alcohol recovery tank;
the salt regeneration zone is provided with 3 ion exchange resin columns 16# -18# -connected in series, a feed inlet of the ion exchange resin columns 16# -18# is communicated with the salt water tank, and a discharge outlet of the ion exchange resin columns 16# -18# is respectively communicated with the waste salt water tank and the sewage treatment channel;
the salt washing area is provided with 3 ion exchange resin columns 13# -15# -connected in series, a feed inlet of the ion exchange resin column 13# -15# is communicated with the pure water tank, and a discharge outlet of the ion exchange resin column 13# -15# is communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# -connected in series, a feed inlet of the ion exchange resin column 10# -12# is communicated with a dilute acid tank, and a discharge outlet of the ion exchange resin column 10# -12# is communicated with a waste acid and sewage treatment channel;
the acid washing area is provided with 3 ion exchange resin columns 7# -9# -connected in series, a feed inlet of the ion exchange resin column 7# -9# is communicated with the pure water tank, and a discharge outlet of the ion exchange resin column 7# -9# is communicated with a 10# ion exchange resin column;
the alkali regeneration zone is provided with 3 ion exchange resin columns 4# -6# -connected in series, a feed port of the ion exchange resin column 4# -6# is communicated with a dilute alkali tank, and a discharge port of the ion exchange resin column 4# -6# is communicated with a waste alkali sewage treatment channel;
the alkali washing zone is provided with 3 ion exchange resin columns 1# -3# -connected in series, a feed inlet of the ion exchange resin column 1# -3# is communicated with the pure water tank, and a discharge outlet of the ion exchange resin column 1# -3# is communicated with a 4# ion exchange resin column;
the device also comprises 4 pure water pumps, wherein the feed inlets of the pure water pumps are communicated with the pure water tank, and the discharge outlets of the 4 pure water pumps are respectively communicated with the ion exchange resin columns 1#, 7#, 13# and 19#, so as to perform top washing on the ion exchange resin columns;
the automatic control system periodically controls each/each group of ion exchange columns through the automatic control valve to realize the processes of separation, elution, salt regeneration, acid regeneration, alkali regeneration and water ejection.
2. An ion exchange system for continuously removing impurities from citicoline sodium as set forth in claim 1 wherein: the dilute alkali tank is filled with 1mol/L NaOH solution, the dilute acid tank is filled with 1mol/L HCl solution, and the brine tank is filled with 4% NaCl solution.
3. An ion exchange system for continuously removing impurities from citicoline sodium as set forth in claim 1 wherein: the alcohol alkali tank is filled with a mixed solution of NaOH solution and ethanol solution, and the preparation method of the mixed solution comprises the following steps: preparing NaOH solution with the concentration of 1mol/L in ethanol water solution with the volume concentration of 20%; the raw material liquid in the raw material liquid tank contains citicoline sodium and impurities, and the impurities contain cytidine acid.
4. An ion exchange system for continuously removing impurities from citicoline sodium as set forth in claim 1 wherein: the plurality of ion exchange resin columns are all anion exchange resin columns.
5. An ion exchange method for continuously removing impurities in citicoline sodium, which is characterized by comprising the following steps:
(1) The method comprises the steps that raw material liquid containing citicoline sodium and impurities enters a continuous ion exchange system, and separation liquid is obtained through adsorption separation in sequence by an ion exchange resin column unit; eluting with alcohol alkali solution to obtain eluent;
(2) The resin column adsorbed and eluted in the step (1) is sequentially subjected to water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment, and the resin column is circularly operated again;
the continuous ion exchange system comprises 30 ion exchange resin columns with the number of 1# -30,
specifically, in the above steps:
the raw material liquid enters 25# and 26# and 28# ion exchange resin columns in parallel through a delivery pump, then enters 29# and 30# ion exchange resin columns in series, and the separated liquid from the 30# ion exchange resin columns enters a product tank and a sewage disposal channel in sections respectively;
eluting: eluting after resin adsorption saturation, providing an eluting raw solution by an alcohol-alkali tank, connecting ion exchange resin columns 22# -24# in series, and feeding the eluting solution into the eluting tank;
washing alcohol alkali: the material in the 19# 21 ion exchange resin column is cleaned by pure water, one part of the material with high ethanol alkali content enters an alcohol recovery tank, and the other part of the material enters a sewage treatment channel to be led to a sewage treatment working section;
salt regeneration: brine is serially connected into a 16# +17# +18# ion exchange resin column, adsorbed cytidine acid impurity and impurity D are eluted, the adsorbed cytidine acid impurity and impurity D enter a sewage treatment channel to be led into a sewage treatment working section, and waste brine enters a waste brine tank;
washing salt: pure water cleans the materials in the ion exchange resin column 13# -15# and the flushing water enters a sewage treatment channel to lead to a sewage treatment working section;
acid regeneration: the ion exchange resin columns 10# 12 are connected in series, and the wastewater enters a waste acid and sewage treatment channel to be led to a sewage treatment working section;
washing with water: washing acid in the 7# 9 ion exchange resin column with pure water, and allowing the effluent and the dilute acid tank feed solution to enter the 10# ion exchange resin column;
alkali regeneration: the ion exchange resin columns # 4 and # 6 are connected in series, and wastewater enters a wastewater treatment channel to be led to a wastewater treatment section;
washing with water to obtain alkali: washing alkali in the 1# -3# ion exchange resin column with pure water, and allowing the effluent and the dilute alkali tank feed solution to enter the 4# ion exchange resin column;
the device also comprises 4 pure water pumps, wherein the feed inlets of the pure water pumps are communicated with the pure water tank, and the discharge outlets of the 4 pure water pumps are respectively communicated with the ion exchange resin columns 1#, 7#, 13# and 19#, so as to perform top washing on the ion exchange resin columns;
the automatic control system periodically controls each/each group of ion exchange columns through the automatic control valve to realize the processes of separation, elution, salt regeneration, acid regeneration, alkali regeneration and water ejection.
6. The ion exchange method for continuously removing impurities in citicoline sodium according to claim 5, wherein said feed solution comprises citicoline sodium and impurities, said impurities comprise cytidine acid, and said 30 ion exchange resin columns have an adsorption capacity for cytidine acid greater than that of citicoline sodium.
7. The ion exchange method for continuously removing impurities in citicoline sodium as claimed in claim 5 wherein the service cycle of the ion exchange resin column is 3 hours, and the flow rate of the upper column is 1.5-2BV.
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5298614A (en) * | 1986-01-06 | 1994-03-29 | Nippon Shinyaku Co. Ltd. | Size limited double stranded poly I poly(cytidylate/4-thiouridylate) |
EP0659483A2 (en) * | 1993-12-27 | 1995-06-28 | Organo Corporation | Continuous ion exchange apparatus |
CN1626547A (en) * | 1998-05-06 | 2005-06-15 | 基因技术股份有限公司 | Protein purification by ion exchange chromatography |
CN1944661A (en) * | 2006-09-28 | 2007-04-11 | 苏州天马医药集团天吉生物制药有限公司 | Process for preparing citicoline sodium |
CN1962875A (en) * | 2006-11-22 | 2007-05-16 | 北京燕京中科生物技术有限公司 | Method for preparing uridine diphosphate |
CN101906126A (en) * | 2010-02-09 | 2010-12-08 | 南京工业大学 | Method for separating purified cytidine diphosphate choline by hydrophobic chromatography |
CN102010454A (en) * | 2010-12-02 | 2011-04-13 | 胡建荣 | Citicoline sodium compound and new method thereof |
CN102605025A (en) * | 2011-01-19 | 2012-07-25 | 中国科学院生物物理研究所 | Bioengineering method for synthesis of citicoline |
CN211585316U (en) * | 2019-07-31 | 2020-09-29 | 赛普特环保技术(厦门)有限公司 | System for continuously removing anions in 3-hydroxy-1, 3, 5-pentanedioic acid |
-
2021
- 2021-07-06 CN CN202110763689.3A patent/CN113769794B/en active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5298614A (en) * | 1986-01-06 | 1994-03-29 | Nippon Shinyaku Co. Ltd. | Size limited double stranded poly I poly(cytidylate/4-thiouridylate) |
EP0659483A2 (en) * | 1993-12-27 | 1995-06-28 | Organo Corporation | Continuous ion exchange apparatus |
CN1626547A (en) * | 1998-05-06 | 2005-06-15 | 基因技术股份有限公司 | Protein purification by ion exchange chromatography |
CN1944661A (en) * | 2006-09-28 | 2007-04-11 | 苏州天马医药集团天吉生物制药有限公司 | Process for preparing citicoline sodium |
CN1962875A (en) * | 2006-11-22 | 2007-05-16 | 北京燕京中科生物技术有限公司 | Method for preparing uridine diphosphate |
CN101906126A (en) * | 2010-02-09 | 2010-12-08 | 南京工业大学 | Method for separating purified cytidine diphosphate choline by hydrophobic chromatography |
CN102010454A (en) * | 2010-12-02 | 2011-04-13 | 胡建荣 | Citicoline sodium compound and new method thereof |
CN102605025A (en) * | 2011-01-19 | 2012-07-25 | 中国科学院生物物理研究所 | Bioengineering method for synthesis of citicoline |
CN211585316U (en) * | 2019-07-31 | 2020-09-29 | 赛普特环保技术(厦门)有限公司 | System for continuously removing anions in 3-hydroxy-1, 3, 5-pentanedioic acid |
Non-Patent Citations (1)
Title |
---|
"胞苷三磷酸的分离纯化";应国清等;中国医药工业杂志;第35卷(第8期);第466-467页2.4树脂的预处理和再生、2.5离子交换过程 * |
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