CN113769794A - 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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- CN113769794A CN113769794A CN202110763689.3A CN202110763689A CN113769794A CN 113769794 A CN113769794 A CN 113769794A CN 202110763689 A CN202110763689 A CN 202110763689A CN 113769794 A CN113769794 A CN 113769794A
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- ion exchange
- exchange resin
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- alkali
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- 229960004774 citicoline sodium Drugs 0.000 title claims abstract description 44
- 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 44
- 239000012535 impurity Substances 0.000 title claims abstract description 38
- 238000005342 ion exchange Methods 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 20
- 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 147
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 147
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 147
- 239000003513 alkali Substances 0.000 claims abstract description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 71
- 238000005406 washing Methods 0.000 claims abstract description 65
- 230000008929 regeneration Effects 0.000 claims abstract description 58
- 238000011069 regeneration method Methods 0.000 claims abstract description 58
- 239000002253 acid Substances 0.000 claims abstract description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- 238000000926 separation method Methods 0.000 claims abstract description 31
- 238000010828 elution Methods 0.000 claims abstract description 25
- 239000003480 eluent Substances 0.000 claims abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000007788 liquid Substances 0.000 claims description 30
- 239000010865 sewage Substances 0.000 claims description 30
- 239000011347 resin Substances 0.000 claims description 25
- 229920005989 resin Polymers 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 24
- 239000002994 raw material Substances 0.000 claims description 19
- 239000002699 waste material Substances 0.000 claims description 17
- 229930183912 Cytidylic acid Natural products 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 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 claims description 10
- 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 claims description 10
- 239000002585 base Substances 0.000 claims description 9
- 238000001179 sorption measurement Methods 0.000 claims description 9
- 239000012267 brine Substances 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- 238000011084 recovery Methods 0.000 claims description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 7
- 239000012527 feed solution Substances 0.000 claims description 5
- 239000003957 anion exchange resin Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 abstract description 5
- 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 description 5
- 239000000463 material Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 3
- 238000010924 continuous production Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 238000004065 wastewater treatment Methods 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
- 239000012190 activator Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process 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
- 239000011538 cleaning material Substances 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007599 discharging 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
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 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
- 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
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
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
Abstract
The invention discloses an ion exchange system and 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 which can move in sequence and rotate circularly, the ion exchange resin column unit comprises a separation area, an elution area, a water washing alcohol alkali area, a salt regeneration area, a water washing salt area, an acid regeneration area, a water washing acid area, an alkali regeneration area and a water washing alkali area, the ion exchange resin columns sequentially move in the separation area, the elution area, the water washing alcohol alkali area, the salt regeneration area, the water washing salt area, the acid regeneration area, the water washing acid area, the alkali regeneration area and the water washing alkali area and rotate circularly, the purity of a discharged product is guaranteed through reasonable configuration, the purity of citicoline sodium of a separation solution and an eluent reaches 99.8%, and the extraction yield is not less than 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
Citicoline sodium is also called citicoline sodium, is a brain metabolism activator, is a nucleoside derivative, is a prerequisite substance of phosphatidylcholine, and is a coenzyme necessary for lecithin synthesis. Researches show that citicoline sodium has the functions of repairing brain injury, resisting oxidation, improving memory and enhancing intelligence, and has wide clinical application.
The conventional chemical synthesis method is used for producing citicoline sodium, the synthesized feed liquid adopts a fixed bed ion exchange process, the manual operation error is large, and the yield is about 85%. The fixed bed process resin has the service cycle of 30 days, the flow rate of the resin on the column is 0.025BV, the material storage time is long, and 20% ethanol is added for bacteriostasis in order to prevent bacteria breeding and prevent ions from being introduced to increase the conductivity. With the column time, citicoline sodium is degraded to produce derivative impurities, resulting in further reduction of yield.
Therefore, the technical problems of low extraction yield and low purity of discharged products in the prior art need to be solved urgently.
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 purpose, the invention adopts the following technical scheme:
an ion exchange system for continuously removing impurities in citicoline sodium; it contains continuous ion exchange resin column unit, ion exchange resin column unit is including a plurality of ion exchange resin columns that can move in proper order, circulation operation, ion exchange resin column unit includes disengagement zone, elution district, washing alcohol alkali district, salt regeneration district, washing salt district, acid regeneration district, washing acid district, alkali regeneration district and washing alkali district, a plurality of ion exchange resin columns are in proper order move in disengagement zone, elution district, washing alcohol alkali district, salt regeneration district, washing salt district, acid regeneration district, washing acid district, alkali regeneration district, washing alkali district in proper order, circulation operation.
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 serial number is 1# -30 #;
the separation area is provided with 6 ion exchange resin columns 25# -30#, the feed inlets of the 25# -30# ion exchange resin columns are communicated with the raw material liquid tank, and the discharge outlets of the 25# -30# ion exchange resin columns are communicated with the product tank and the sewage discharge channel;
the elution area is provided with 3 ion exchange resin columns 22# -24# connected in series, the feed inlet of the 22# -24# ion exchange resin column is communicated with the alcohol-base tank, and the discharge outlet of the 22# -24# ion exchange resin column is communicated with the elution tank;
the water washing alcohol-alkali area is provided with 3 ion exchange resin columns 19# -21# connected in series, the feed inlets of the 19# -21# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 19# -21# ion exchange resin columns are 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, the feed inlets of the 16# -18# ion exchange resin columns are communicated with the brine tank, and the discharge outlets of the 16# -18# ion exchange resin columns are respectively communicated with the waste salt tank and the sewage treatment channel;
the water washing salt area is provided with 3 ion exchange resin columns 13# -15# connected in series, the feed inlets of the 13# -15# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 13# -15# ion exchange resin columns are communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# connected in series, the feed inlets of the 10# -12# ion exchange resin columns are communicated with a dilute acid tank, and the discharge outlets of the 10# -12# ion exchange resin columns are communicated with a waste acid sewage treatment channel;
the water acid washing area is provided with 3 ion exchange resin columns 7# -9# connected in series, the feed inlets of the 7# -9# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 7# -9# ion exchange resin columns are communicated with the 10# ion exchange resin column;
the alkali regeneration zone is provided with 3 ion exchange resin columns 4# -6# connected in series, the feed inlet of the 4# -6# ion exchange resin column is communicated with a dilute alkali tank, and the discharge outlet of the 4# -6# ion exchange resin column is communicated with a waste alkali sewage treatment channel;
the alkali washing area is provided with 3 ion exchange resin columns 1# -3# connected in series, the feed inlets of the 1# -3# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 1# -3# ion exchange resin columns are communicated with the 4# ion exchange resin column.
Further, the device also comprises 4 pure water pumps, wherein feed inlets of the pure water pumps are communicated with the pure water tank, and discharge outlets of the 4 pure water pumps are respectively communicated with the 1#, 7#, 13# and 19# ion exchange resin columns in a one-to-one correspondence manner so as to carry out top washing on the ion exchange resin columns.
Furthermore, 1mol/L NaOH solution is contained in the dilute alkali tank, 1mol/L HCl solution is contained in the dilute acid tank, and NaCl solution with the mass concentration of 4% is contained in the saline water tank.
Further, the alcohol-alkali tank is filled with a mixed solution of a NaOH solution and an ethanol solution, and the preparation method of the mixed solution comprises the following steps: preparing a NaOH solution with the concentration of 1mol/L in an ethanol aqueous solution with the volume concentration of 20%; the feed solution in the feed solution tank comprises citicoline sodium and impurities, the impurities comprising cytidylic acid.
Further, the plurality of ion exchange resin columns are all anion exchange resin columns.
The invention also provides an ion exchange method for continuously removing impurities in citicoline sodium, which comprises the following steps:
(1) 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-base solution to obtain eluent;
(2) and (2) sequentially carrying out water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment on the resin column adsorbed and eluted in the step (1), and circularly operating again.
Further, the continuous ion exchange system comprises 30 ion exchange resin columns with numbers of 1# -30#, and the process of obtaining the separation liquid by adsorption separation in the step (1) is as follows:
the raw material liquid enters 25# +27# and 26# +28# ion exchange resin columns in parallel through a delivery pump, then enters 29# +30# ion exchange resin columns in series, and the separation liquid from 30# ion exchange resin column enters a product tank and a sewage discharge channel in stages respectively.
Further, the raw material liquid comprises citicoline sodium and impurities, the impurities comprise cytidylic acid, and the adsorption capacity of the 30 ion exchange resin columns on the cytidylic acid is greater than that of the citicoline sodium.
Further, the service cycle of the ion exchange resin column is 3h, and the flow rate of the ion exchange resin column is 1.5-2 BV.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a continuous ion exchange system for citicoline sodium production, which 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 in sequence and running in a circulating manner, 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 ion exchange resin columns sequentially move and 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 discharging product purity is ensured through reasonable configuration, the citicoline sodium purity of a separation solution and an eluent reaches 99.8%, and the extraction yield is not less than 96%;
(2) the resin of the ion exchange system provided by the invention has the service cycle of 3h, the flow rate of the resin on the column is 1.5-2BV, the treatment speed is high, the material storage time is short, no ethanol is required to be added for bacteriostasis, and the addition of raw material liquid ethanol is avoided;
(3) the invention reduces the consumption of regenerated acid and alkali, reduces the cost and is more environment-friendly through the control of the process;
(4) the invention realizes full automation 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 impurities from citicoline sodium according to the present invention.
Reference numerals:
11. ion exchange resin column, 12 raw material liquid tank, 13 product tank, 14 alcohol-alkali tank, 15 elution tank, 16 pure water tank, 17 alcohol recovery tank, 18 brine tank, 19 waste salt tank, 20 dilute acid tank, and 21 dilute alkali tank.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Referring to fig. 1, the present invention provides an ion exchange system for continuously removing impurities from 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 capable of sequentially moving and circularly operating, the ion exchange resin column unit comprises a separation zone, an elution zone, a washed alcohol-alkali zone, a salt regeneration zone, a washed salt zone, an acid regeneration zone, a washed acid zone, an alkali regeneration zone and a washed alkali zone, and the plurality of ion exchange resin columns 11 sequentially move and circularly operate in the separation zone, the elution zone, the washed alcohol-alkali zone, the salt regeneration zone, the washed salt zone, the acid regeneration zone, the washed acid zone, the washed alkali regeneration zone and the washed alkali zone.
Referring to fig. 1, the ion exchange system for continuously removing impurities from citicoline sodium provided by this embodiment further includes a raw material liquid tank 12, a product tank 13, an alcohol-base 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 base tank 21; the total number of the ion exchange resin columns 11 is 30, and the serial number is 1# -30 #;
the separation area is provided with 6 ion exchange resin columns 25# -30#, the feed inlets of the 25# -30# ion exchange resin columns are communicated with the raw material liquid tank 12, and the discharge outlets of the 25# -30# ion exchange resin columns are communicated with the product tank 13 and the sewage discharge channel;
the elution area is provided with 3 ion exchange resin columns 22# -24# connected in series, the feed inlet of the 22# -24# ion exchange resin column is communicated with the alcohol-base tank 14, and the discharge outlet of the 22# -24# ion exchange resin column is communicated with the elution tank 15;
the water washing alcohol-alkali area is provided with 3 ion exchange resin columns 19# -21# connected in series, the feed inlets of the 19# -21# ion exchange resin columns are communicated with a pure water tank 16, and the discharge outlets of the 19# -21# ion exchange resin columns are 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, the feed inlets of the 16# -18# ion exchange resin columns are communicated with a brine tank 18, and the discharge outlets of the 16# -18# ion exchange resin columns are respectively communicated with a waste salt tank 19 and a sewage treatment channel;
the water washing salt area is provided with 3 ion exchange resin columns 13# -15# connected in series, the feed inlets of the 13# -15# ion exchange resin columns are communicated with a pure water tank 16, and the discharge outlets of the 13# -15# ion exchange resin columns are communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# connected in series, the feed inlet of the 10# -12# ion exchange resin column is communicated with a dilute acid tank 20, and the discharge outlet of the 10# -12# ion exchange resin column is communicated with a waste acid sewage treatment channel;
the water acid washing area is provided with 3 ion exchange resin columns 7# -9# connected in series, the feed inlet of the 7# -9# ion exchange resin column is communicated with a pure water tank 16, and the discharge outlet of the 7# -9# ion exchange resin column 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, the feed inlet of the 4# -6# ion exchange resin column is communicated with a dilute alkali tank 21, and the discharge outlet of the 4# -6# ion exchange resin column is communicated with a waste alkali sewage treatment channel;
the alkali washing area is provided with 3 ion exchange resin columns 1# -3# connected in series, the feed inlet of the 1# -3# ion exchange resin column is communicated with a pure water tank 16, and the discharge outlet of the 1# -3# ion exchange resin column is communicated with a 4# ion exchange resin column.
The embodiment further comprises 4 pure water pumps (not marked 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#, 7#, 13# and 19# ion exchange resin columns in a one-to-one correspondence manner so as to carry out top washing on the ion exchange resin columns.
The present 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 the sewage treatment channel with the ion exchange resin column 11, and the like, and the automatic control system periodically controls each/each group of ion exchange columns through the automatic control valve to realize the separation, elution, salt regeneration, acid regeneration, alkali regeneration and water-lifting processes. The automatic control system of the invention periodically controls each group of ion exchange columns through the automatic control valve to realize the separation, elution, salt regeneration, acid regeneration, alkali regeneration and water-lifting processes, and reasonably configures to ensure the purity of discharged products. The whole-process automatic and continuous production is realized through the continuous ion exchange system, and the efficiency is improved.
In the embodiment, a dilute alkali tank 21 is filled with 1mol/L NaOH solution, a dilute acid tank 20 is filled with 1mol/L HCl solution, and a brine tank 18 is filled with 4% NaCl solution; the alcaline tank 14 is filled with a mixed solution of ethanol solution and NaOH, and the preparation method of the mixed solution comprises the following steps: preparing a NaOH solution with the final concentration of 1mol/L in an ethanol aqueous solution with the volume concentration of 20%; the raw material liquid in the raw material liquid tank 12 contains citicoline sodium and impurities including cytidylic acid and an impurity D of unknown composition.
Through liquid chromatography test, the liquid chromatography peak of citicoline sodium appears at 4.5min, the impurity cytidylic acid peak appears at about 7min, and the impurity D of unknown components appears at about 24.5 min. The ion exchange resin column used in the invention has the weakest adsorption capacity on citicoline sodium, and can be eluted by using alcohol-base mixed solution (namely the mixed solution of the ethanol solution and the NaOH solution); the adsorption capacity to the impurity D is the second, and the adsorption capacity to the impurity B is the strongest.
The ion exchange resin column used in this example was packed with an anion exchange resin (85% by volume of the resin column) from Shandong Zibo Daihong chemical Co., Ltd. The service cycle of the ion exchange resin column is 3h, and the flow rate of the ion exchange resin column on the column is 1.5-2BV
The process of separating the product and regenerating the resin of the ion exchange system for continuously removing impurities from citicoline sodium provided by the embodiment is as follows, that is, the ion exchange method for continuously removing impurities from citicoline sodium comprises the following steps:
(1) 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-base solution to obtain eluent;
(2) and (2) sequentially carrying out water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment on the resin column adsorbed and eluted in the step (1), and circularly operating again.
Specifically, the steps are as follows:
separation (25-30 #): raw material liquid is parallelly connected into a 25# +27#/26# +28# resin column through a delivery pump, and then is serially connected into a 29# +30# resin column, separation liquid from the 30# resin column is collected in sections, no content enters a sewage discharge pipeline at one section, and the purity of a product reaches the standard at the other section and enters a product tank;
elution (22-24 #): after the resin is adsorbed and saturated, eluting, wherein an alcohol-alkali tank provides an elution stock solution, three resin columns are connected in series, and an eluent enters an elution tank;
water-washed alcohol alkali (19-21 #): the pure water cleans the materials in the resin column, one part (section I) of the pure water enters an alcohol recovery tank with high ethanol alkali content, and the other part (section II) of the pure water enters a sewage treatment channel and leads to a sewage treatment section;
salt regeneration (16-18 #): the saline water is connected in series to enter a 16# +17# +18# resin column, adsorbed impurity cytidylic acid and impurity D are eluted, the eluted impurity cytidylic acid and impurity D enter a sewage treatment channel and lead to a sewage treatment working section, and the waste saline water enters a waste salt tank;
washing salt with water (13-15 #): cleaning materials in the resin column by pure water, and introducing washing water into a sewage treatment channel to a sewage treatment section;
acid regeneration (10-12 #): three resin columns are connected in series, and wastewater enters a waste acid and sewage treatment channel and leads to a sewage treatment section;
washing with water acid (7-9 #): washing acid in the resin column with pure water, and allowing effluent liquid and dilute acid tank feed liquid to enter the resin column No. 10;
alkali regeneration (4-6 #): three resin columns are connected in series, and wastewater enters a waste alkali wastewater treatment channel and leads to a wastewater treatment working section;
alkali washing with water (1-3 #): and (4) washing the alkali in the resin column by pure water, and allowing the effluent and the feed liquid in the dilute alkali tank to enter the resin column.
The system and the method are used for processing 3 different batches of raw materials, and the content, purity and yield results of the discharged citicoline sodium are shown in table 1.
TABLE 1 discharge of citicoline sodium treated according to the invention
As can be seen from Table 1, the product purity is improved to over 99.8% and the yield is over 96% after the separation by the technical scheme provided by the invention.
The resin of the ion exchange system provided by the invention has the service cycle of 3h, the flow rate of the resin on the column is 1.5-2BV, the treatment speed is high, the material storage time is short, no ethanol is required to be added for bacteriostasis, and the addition of raw material liquid ethanol is avoided; the invention reduces the consumption of regenerated acid and alkali, reduces the cost and is more environment-friendly through the control of the process.
The above description is only a preferred embodiment 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 are also within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. An ion exchange system for continuously removing impurities in citicoline sodium is characterized in that: contain continuous ion exchange resin column unit, ion exchange resin column unit is including a plurality of ion exchange resin columns that can move in proper order, circulation operation, ion exchange resin column unit includes separation zone, elution district, washing alcohol alkali district, salt regeneration district, washing salt district, acid regeneration district, washing acid district, alkali regeneration district and washing alkali district, a plurality of ion exchange resin columns are in proper order move in separation zone, elution district, washing alcohol alkali district, salt regeneration district, washing salt district, acid regeneration district, washing acid regeneration district, alkali regeneration district, washing alkali district in proper order, circulation operation.
2. The ion exchange system for continuously removing impurities from citicoline sodium of claim 1 further comprising: 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 serial number is 1# -30 #;
the separation area is provided with 6 ion exchange resin columns 25# -30#, the feed inlets of the 25# -30# ion exchange resin columns are communicated with the raw material liquid tank, and the discharge outlets of the 25# -30# ion exchange resin columns are communicated with the product tank and the sewage discharge channel;
the elution area is provided with 3 ion exchange resin columns 22# -24# connected in series, the feed inlet of the 22# -24# ion exchange resin column is communicated with the alcohol-base tank, and the discharge outlet of the 22# -24# ion exchange resin column is communicated with the elution tank;
the water washing alcohol-alkali area is provided with 3 ion exchange resin columns 19# -21# connected in series, the feed inlets of the 19# -21# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 19# -21# ion exchange resin columns are 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, the feed inlets of the 16# -18# ion exchange resin columns are communicated with the brine tank, and the discharge outlets of the 16# -18# ion exchange resin columns are respectively communicated with the waste salt tank and the sewage treatment channel;
the water washing salt area is provided with 3 ion exchange resin columns 13# -15# connected in series, the feed inlets of the 13# -15# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 13# -15# ion exchange resin columns are communicated with a sewage treatment channel;
the acid regeneration zone is provided with 3 ion exchange resin columns 10# -12# connected in series, the feed inlets of the 10# -12# ion exchange resin columns are communicated with a dilute acid tank, and the discharge outlets of the 10# -12# ion exchange resin columns are communicated with a waste acid sewage treatment channel;
the water acid washing area is provided with 3 ion exchange resin columns 7# -9# connected in series, the feed inlets of the 7# -9# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 7# -9# ion exchange resin columns are communicated with the 10# ion exchange resin column;
the alkali regeneration zone is provided with 3 ion exchange resin columns 4# -6# connected in series, the feed inlet of the 4# -6# ion exchange resin column is communicated with a dilute alkali tank, and the discharge outlet of the 4# -6# ion exchange resin column is communicated with a waste alkali sewage treatment channel;
the alkali washing area is provided with 3 ion exchange resin columns 1# -3# connected in series, the feed inlets of the 1# -3# ion exchange resin columns are communicated with the pure water tank, and the discharge outlets of the 1# -3# ion exchange resin columns are communicated with the 4# ion exchange resin column.
3. The ion exchange system for continuously removing impurities from citicoline sodium according to claim 2, wherein: still include 4 pure water pumps, the feed inlet intercommunication of pure water pump the pure water jar, 4 pure water pump's discharge gate respectively one-to-one intercommunication 1#, 7#, 13# and 19# ion exchange resin post to carry out the top to washing to ion exchange resin post.
4. The ion exchange system for continuously removing impurities from citicoline sodium according to claim 2, wherein: the diluted alkali tank is filled with 1mol/L NaOH solution, the diluted acid tank is filled with 1mol/L HCl solution, and the saline water tank is filled with NaCl solution with mass concentration of 4%.
5. The ion exchange system for continuously removing impurities from citicoline sodium according to claim 2, wherein: the alcohol-alkali tank is filled with mixed solution of NaOH solution and ethanol solution, and the preparation method of the mixed solution comprises the following steps: preparing a NaOH solution with the concentration of 1mol/L in an ethanol aqueous solution with the volume concentration of 20%; the feed solution in the feed solution tank comprises citicoline sodium and impurities, the impurities comprising cytidylic acid.
6. The ion exchange system for continuously removing impurities from citicoline sodium of claim 1 further comprising: the ion exchange resin columns are all anion exchange resin columns.
7. An ion exchange method for continuously removing impurities in citicoline sodium is characterized by comprising the following steps:
(1) 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-base solution to obtain eluent;
(2) and (2) sequentially carrying out water washing alcohol alkali, salt regeneration, water washing salt, acid regeneration, water washing acid, alkali regeneration and water washing alkali treatment on the resin column adsorbed and eluted in the step (1), and circularly operating again.
8. The ion exchange method for continuously removing impurities in citicoline sodium according to claim 7, wherein said continuous ion exchange system comprises 30 ion exchange resin columns, which are numbered from # 1 to # 30, and the process of obtaining the separation liquid by adsorption separation in step (1) is as follows:
the raw material liquid enters 25# +27# and 26# +28# ion exchange resin columns in parallel through a delivery pump, then enters 29# +30# ion exchange resin columns in series, and the separation liquid from 30# ion exchange resin column enters a product tank and a sewage discharge channel in stages respectively.
9. The ion exchange process for continuously removing impurities from citicoline sodium according to claim 8, wherein said feed solution comprises citicoline sodium and impurities, said impurities comprise cytidylic acid, and said 30 ion exchange resin columns have a greater affinity for cytidylic acid than for citicoline sodium.
10. The ion exchange process for continuously removing impurities from citicoline sodium according to claim 7, wherein the cycle time of the ion exchange resin column is 3 hours and the flow rate of the ion exchange resin column is 1.5-2 BV.
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| CN115057901A (en) * | 2022-07-12 | 2022-09-16 | 赛普特环保技术(厦门)有限公司 | Nucleoside purification system and purification process |
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