CN107722040A - A kind of membrane separating method and device for recycling ceftazidime mother liquor - Google Patents
A kind of membrane separating method and device for recycling ceftazidime mother liquor Download PDFInfo
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- CN107722040A CN107722040A CN201710933448.2A CN201710933448A CN107722040A CN 107722040 A CN107722040 A CN 107722040A CN 201710933448 A CN201710933448 A CN 201710933448A CN 107722040 A CN107722040 A CN 107722040A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
- B01D61/027—Nanofiltration
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A20/00—Water conservation; Efficient water supply; Efficient water use
- Y02A20/124—Water desalination
- Y02A20/131—Reverse-osmosis
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- Organic Chemistry (AREA)
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- Nanotechnology (AREA)
- Water Supply & Treatment (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention belongs to pharmaceutical technology field, is related to a kind of membrane separating method and device for recycling ceftazidime mother liquor.Cefotaxime belongs to third generation antibiotic, has wider application than other third generation cephalosporin analog antibiotics.At present in the production technology of cefotaxime, due to the salting-out effect of mother liquor in crystallization processes, the yield of cefotaxime only has 82%, and also 18% in mother liquor, this not only adds production cost, and no small pollution is caused to environment.The present invention recycles to the product in mother liquor using the adjustment of membrane separation technique and technique, has greatly saved pollution of the production cost reduction to environment, the device is simple to operate, easily realizes industry amplification.
Description
Technical field
The invention belongs to field of biological pharmacy, and in particular to a kind of characteristic using material in itself, pass through special film group
The isolation technics of part integrated modular device extracts the new technology and device of cefotaxime from cefotaxime crystal solution.
Background technology
Ploughed according to Wang Rong in the finely report with specialty chemicals periodical：Cefotaxime belongs to third generation cephalo-type antibiosis
Element, it was found in 1978,1983, Ge Lansu companies of Britain are developed listing first.1992, cefotaxime
In China's Initial Public Offering, China's essential drug list is formally included within 1993.Verified by the clinical practices of more than 10 years, head
His pyridine of spore has the characteristics that has a broad antifungal spectrum, resistance to enzyme, and its antibacterial activity to pseudomonas aeruginosa is stronger, is widely used in treating
In various, severe infection, be treatment infection gram-negative bacteria critical patient choice drug.
It is reported that Pseudomonas aeruginosa inside-hospital infection be most extensively, most serious the problem of one of, account for inside-hospital infection 9 ~
10%, reach 18 ~ 20% individually.Because Pseudomonas aeruginosa has drug resistance to Multiple Classes of Antibiotics, very big be stranded is brought to clinical treatment
Difficulty, so significant to the expanding production of the cefotaxime medicine of anti Bacillus pyocyaneu Flugge.
At present, document report, which prepares cefotaxime, two kinds of different methods：First method is with 7- amino cephalo alkane
Sour (7-ACA) is starting parent nucleus, is reacted in the presence of Iodotrimethylsilane (TMSI) with pyridine, obtains the hydrochloric acid of 7-APCA bis-
Salt, the disalt react with BPTA, obtain the cefotaxime tert-butyl ester, and the tert-butyl ester is again through steps such as hydrolysis
Ceftazidime pentahydrate is obtained, pentahydrate is mixed and made into injection bulk drug with sodium carbonate.Second method is with 7- benzene second
Acid amides -3- chloromethyl cephalosporin alkyl acid p-methoxybenzyl esters (GCLE) are starting parent nucleus, with iodate nak response, obtain cefotaxime
Intermediate 7- phenylacetylamino -3- iodomethyl -3- cephalosporin-4-carboxyl acids carry out parent to methoxybenzyl ester, the intermediate with pyridine
The series reactions such as core substitution obtain target product.
No matter which kind of synthesis path used, last crystallization and purification method is all the crystallization of cefotaxime hydrochloride salt, by
In salting-out effect, cefotaxime solubility in water is considerably increased, therefore, the primary crystallization yield of cefotaxime only has 87%,
Also 13% in mother liquor, this not only adds the production cost of cefotaxime, but also no small pollution is caused to environment.
And traditional handicraft adjusts isoelectric point with phosphoric acid, due to being trivalent salt, molecular weight approaches with cefotaxime, and nano filtering process is difficult that removing is inorganic
Salt, isoelectric point is adjusted with hydrochloric acid, because hydrochloric acid is to the severe corrosive of stainless steel, the production for sterile bulk drug is to equipment damage
Greatly, thereby increases and it is possible to bring metal into medicine.
The present invention is recycled, greatly using the adjustment of membrane separation technique and technique to the product in mother liquor
Pollution of the production cost reduction to environment is saved；The device is simple to operate simultaneously, easily realizes industry amplification.
The content of the invention
The shortcomings that in order to overcome traditional handicraft, the invention provides a kind of UF membrane side for recycling ceftazidime mother liquor
Method and device.
In the method, the new crystallization processes of cefotaxime are relate to, it is formic acid to crystallize acid used, is solved to equipment
Etching problem, while the product in mother liquor is recycled using membrane separation technique, adds product yield, reduce
Environmental pollution.
Present invention also offers from cefotaxime crystalline mother solution reclaim product complexes, that is, recycle cephalo he
The membrane separation device of pyridine mother liquor, and the method that ceftazidime mother liquor recycles is realized in the apparatus.
It is specific the technical scheme is that：
A kind of membrane separating method for recycling ceftazidime mother liquor, it is characterised in that：This method comprises the following steps
（1）The temperature of reactor reclaimed water is maintained at 0-5 DEG C, cefotaxime hydrochloride is added, dissolving, sodium hydroxide is added dropwise, adjust
PH to 5.5-5.6, filtering, crystallizing tank is transferred to by filtrate；
（2）Feed temperature is maintained at 0-5 DEG C, pH to 4.3-4.4 is adjusted with slow acid, goes out crystalline substance, stops being added dropwise, growing the grain is after 2 hours
Continuously add acid, stop being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours；
（3）Separation of solid and liquid, cefotaxime crystallization yield now is 82%, and the mother liquor after filtering is collected and is transferred to head tank；
（4）Crystalline mother solution in head tank adjusts pH to 4.8-5.0 with sodium hydroxide solution；
（5）Mother liquor carries out desalination using nano-filtration membrane equipment, and in desalting processing, it is 4.3-4.4 to be adjusted with acid and keep the pH of mother liquor,
And with pure water dilute desalination, until salt rejection rate reach more than 99%；
（6）The mother liquor of removing salinity is concentrated using membrane separation technique, and mother liquid concentration is concentrated into more than 6% from 0.5%；
（7）Desalting mother liquor is transferred to crystallization kettle, is cooled to 0-5 DEG C, with acid for adjusting pH to 4.3-4.4, goes out crystalline substance, stops being added dropwise,
Growing the grain continuously adds acid after 2 hours, stop being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours；Separation of solid and liquid is carried out, is obtained
Cefotaxime crystal, cefotaxime crystal obtain final products through recrystallization.
In the method, the acid for adjusting pH is phosphoric acid, hydrochloric acid or formic acid, wherein it is preferred that formic acid is as pH adjusting agent.
A kind of membrane separation device for recycling ceftazidime mother liquor, it is characterised in that the device contains modular pure water
Tank（1）, raw material tank arrangement（2）, purge tank（3）, formic acid tank（4）, discharging pump（5）, charging pump（6）, high-pressure pump（7）, circulating pump
（8）, cartridge filter（9）, heat exchanger（10）, NF membrane and membrane module（11）, connecting pipeline and Automated condtrol system；
Wherein, pure water tank（1）, raw material tank arrangement（2）, purge tank（3）Discharging opening and discharging pump（5）, charging pump（6）UNICOM, supply
Expect pump（6）With cartridge filter（9）UNICOM；Formic acid tank（4）With cartridge filter（9）UNICOM；Cartridge filter（9）With heat exchanger
（10）UNICOM；Heat exchanger（10）With high-pressure pump（7）；High-pressure pump（7）With circulating pump（8）UNICOM；Circulating pump（8）With NF membrane and film
Component（11）Feed inlet end UNICOM；NF membrane and membrane module（11）Discharge port end and pure water tank（1）, raw material tank arrangement（2）, cleaning
Tank（3）UNICOM；
Wherein, the control device of automation, include the on-line checking and control system of pH value, pass through on-line checking formic acid tank（4）
With cartridge filter（9）PH value, and control enter formic acid tank（4）With cartridge filter（9）The folding of outlet valve, realize
The On-line Control of pH value；Also flow sensor is provided with including pump（20）~（22）, pressure sensor（14）、（17）、（18）And control
Device processed, flow sensor（19）、（20）、（22）The pressure and data on flows imported and exported in pump are gathered with pressure sensor, and is passed
Transport to controller（12）、（16）、（21）, data reception module, processing module and communication module, data receiver are provided with controller
Module is transferred to processing module after receiving the data message of two sensor transmissions, is finally transmitted again via communication module to service
Terminal；Service terminal receives the data message that controller is sent, and is shown in its display screen.
The method that ceftazidime mother liquor is recycled using device of the present invention, it is characterised in that:Mother liquor enters pan feeding
Tank（2）PH to 4.8-5.0 is adjusted with sodium hydroxide solution afterwards, passes through charging pump（6）, by cartridge filter（9）, then by changing
Hot device（10）, the temperature of feed liquid is maintained at 0-5 DEG C, then by high-pressure pump（7）, circulating pump（8）, into NF membrane（11）Taken off
Salt, the salt solution of transmission enter sewerage, circulation fluid feed back tank（2）, the mother liquor after desalination passes through discharging pump（5）Into crystallization kettle
Carry out secondary crystallization..
Method of the present invention, wherein, mother liquor is popped one's head in desalination processes by pH（13）, and digital controlled valve（12）
Automatic feedback feed supplement is carried out, by formic acid tank（4）In formic acid add mother liquor in, it is 4.3-4.4 to keep its pH value.
Method of the present invention, wherein, by pure water tank（1）In pure water be supplemented to film filter module, ensure desalination
Pure water supplements in journey, purge tank（3）In water for cleaning injection film filter module, ensure nanofiltration film module normal operation.
Method of the present invention, wherein, the film is special membrane, model ZK008-2.Special type point in the present invention
From membrane derived in GE companies NF membrane, model ZK008-2.In another preferable scheme, the special separation film is by GE companies
Obtained by nanofiltration membrane modifying, molecular cut off is 200 dalton, Nacl rejections 85%；Modified film feature is to cefotaxime
Rejection is high, good to formates permeability, and resistance tocrocking is good, and easy cleaning regeneration recovers flux.
The beneficial effects of the present invention are：
（1）The present invention is formic acid in the acid used in cefotaxime crystallization processes, overcomes traditional handicraft and adjusts isoelectric point with phosphoric acid, by
Then trivalent salt, molecular weight approach with cefotaxime, and nano filtering process is difficult to remove inorganic salts, isoelectric point are adjusted with hydrochloric acid, due to hydrochloric acid
To the severe corrosive of stainless steel, the production for sterile bulk drug is big to equipment damage, thereby increases and it is possible to brings metal into medicine.This
Sample is advantageous to the mother liquor desalination of cefotaxime, so as to reclaim cefotaxime product.
（2）All operations of the present invention have carried out integrated modular, and by touch-screen centralized Control, the quality of product is steady
It is fixed, while save human cost.Pump is provided with flow sensor, pressure sensor and controller, flow sensor and pressure
The pressure and data on flows imported and exported in sensor collection pump, and transmit to controller, be provided with controller data reception module,
Processing module and communication module, data reception module are transferred to processing module after receiving the data message of two sensor transmissions,
Finally transmitted again via communication module to service terminal；Service terminal receives the data message that controller is sent, and is shown in it
Display screen.
（3）The film device that the present invention uses, compared with traditional common NF membrane, have contamination resistance strong, cleaning is easy
Characteristic.
Brief description of the drawings
Fig. 1 recycles the membrane separation device of ceftazidime mother liquor.Wherein,（1）For pure water tank；（2）For head tank；（3）
For purge tank；（4）For formic acid tank；（5）For discharging pump；（6）For charging pump；（7）For high-pressure pump；（8）For circulating pump；（9）To protect
Pacify filter；（10）For heat exchanger；（11）For NF membrane；（12）For digital controlled valve；（13）Popped one's head in for PH；（14）For pressure gauge；
（15）For thermometer；（16）For digital controlled valve；（17）For pressure gauge；（18）For pressure gauge；（19）For numerical control recorder；（20）For
Flowmeter；（21）For digital controlled valve；（22）For flowmeter.
The chemical constitution of Fig. 2 ceftazidime pentahydrates.
Embodiment
Embodiment 1：This example demonstrates that the composition of the complete set of equipments from the desalter of cefotaxime mother liquor reclaiming method
And annexation
The schematic diagram of the complete set of equipments is as shown in Figure 1.The specific equipment contains modular pure water tank（1）, raw material tank arrangement
（2）, purge tank（3）, formic acid tank（4）, discharging pump（5）, charging pump（6）, high-pressure pump（7）, circulating pump（8）, cartridge filter
（9）, heat exchanger（10）, NF membrane and membrane module（11）, connecting pipeline and Automated condtrol system.
Wherein, pure water tank（1）, raw material tank arrangement（2）, purge tank（3）Discharging opening and discharging pump（5）, charging pump（6）Connection
It is logical, charging pump（6）With cartridge filter（9）UNICOM；Formic acid tank（4）With cartridge filter（9）UNICOM；Cartridge filter（9）With
Heat exchanger（10）UNICOM；Heat exchanger（10）With high-pressure pump（7）；High-pressure pump（7）With circulating pump（8）UNICOM；Circulating pump（8）With nanofiltration
Film and membrane module（11）Feed inlet end UNICOM；NF membrane and membrane module（11）Discharge port end and pure water tank（1）, raw material tank arrangement
（2）, purge tank（3）UNICOM.
Wherein, the control device of automation, include the on-line checking and control system of pH value, pass through on-line checking formic acid tank
（4）With cartridge filter（9）PH value, and control enter formic acid tank（4）With cartridge filter（9）The folding of outlet valve,
Realize the On-line Control of pH value；Also flow sensor is provided with including pump（20）~（22）, pressure sensor（14）、（17）、（18）
And controller, flow sensor（19）、（20）、（22）The pressure and data on flows imported and exported in pump are gathered with pressure sensor,
And transmit to controller（12）、（16）、（21）, data reception module, processing module and communication module, data are provided with controller
Receiving module receive two sensor transmissions data message after be transferred to processing module, finally again via communication module transmit to
Service terminal；Service terminal receives the data message that controller is sent, and is shown in its display screen.
Wherein, the special membrane is GE companies NF membrane, model ZK008-2.
Embodiment 2：This example demonstrates that the technique of cefotaxime is reclaimed after desalination from ceftazidime mother liquor
Reactor reclaimed water is cooled to 0-5 DEG C, adds cefotaxime hydrochloride, dissolving.Sodium hydroxide is added dropwise, adjusts pH to 5.5-
5.6, filter to crystallizing tank.Maintain feed temperature slowly to adjust PH4.3-4.4 with formic acid at 0-5 DEG C, go out crystalline substance, stop being added dropwise, support
Formic acid is continuously added after brilliant 2 hours, stops being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours.Separation of solid and liquid, mother liquor are collected and beaten
Enter tank（2）, cefotaxime crystallization yield now is 87%.In tank（2）In crystalline mother solution first with sodium hydroxide solution adjust pH
To 4.8-5.0.Mother liquor carries out desalting processing using membrane separation technique, and the pH of mother liquor is constantly adjusted extremely with formic acid in desalting processing
4.3-4.4, behind with pure water dilute desalination, final salt rejection rate reaches more than 90%.Desalting mother liquor returns crystallization kettle, is cooled to
0-5 DEG C, pH to 4.3-4.4 is slowly adjusted with formic acid, goes out crystalline substance, stops being added dropwise, growing the grain continuously adds formic acid after 2 hours, adjust pH extremely
Stop being added dropwise after 3.6-3.7, then growing the grain 4 hours.Then, separation of solid and liquid is carried out, obtained cefotaxime crystal is carried out once again
Recrystallization can obtain qualified product, and total recovery now reaches 95%.
Embodiment 3：This example demonstrates that implement the situation of present invention process in the equipment of embodiment
Take 50kg cefotaximes hydrochloride to be dissolved in 500L pure water in 800L stainless steel cauldrons, 0-5 DEG C be cooled to refrigerant,
Mixing speed is 80 turns/min, and the pH to 5.5-5.6 of regulation solution is added dropwise with 5N sodium hydroxide solutions, then filters, filtered fluid
Return to crystallization kettle, maintain feed temperature slowly to adjust pH to 4.3-4.4 with formic acid at 0-5 DEG C, go out crystalline substance, stop being added dropwise, growing the grain
Continuously add formic acid after 2 hours, stop being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours.Separation of solid and liquid, mother liquor are collected and squeezed into
Desalter head tank（2）, in tank（2）In crystalline mother solution first with sodium hydroxide solution adjust pH to 4.8-5.0.Mother liquor utilizes
Membrane separation technique carries out desalting processing, constantly adjusts the pH to 4.3-4.4 of mother liquor with formic acid in desalting processing, behind use pure water
Desalination is diluted, final salt rejection rate reaches more than 99%.Desalting mother liquor returns crystallization kettle, is cooled to 0-5 DEG C, is slowly adjusted with formic acid
PH to 4.3-4.4 is saved, goes out crystalline substance, stops being added dropwise, growing the grain continuously adds formic acid after 2 hours, stop being added dropwise after adjusting pH to 3.6-3.7,
Growing the grain 4 hours again.Then, carry out separation of solid and liquid, obtained cefotaxime crystal once recrystallized again can obtain it is qualified
Product, total recovery now reaches 94.89%.
Embodiment 4：This example demonstrates that implement the situation of present invention process in the equipment of embodiment
Take 50kg cefotaximes hydrochloride to be dissolved in 500L pure water in 800L stainless steel cauldrons, 0-5 DEG C be cooled to refrigerant,
Mixing speed is 80rmin, and the pH to 5.5-5.6 of regulation solution is added dropwise with 5N sodium hydroxide solutions, then filters, filtered fluid is beaten
Crystallization kettle is back to, maintains feed temperature slowly to adjust pH to 4.3-4.4 with formic acid at 0-5 DEG C, goes out crystalline substance, stops being added dropwise, growing the grain 2
Formic acid is continuously added after hour, stops being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours.Separation of solid and liquid, mother liquor are collected and squeezed into
Desalter head tank（2）, in tank（2）In crystalline mother solution first with sodium hydroxide solution adjust pH to 4.8-5.0.Mother liquor utilizes
Membrane separation technique carries out desalting processing, constantly adjusts the pH to 4.3-4.4 of mother liquor with formic acid in desalting processing, behind use pure water
Desalination is diluted, final salt rejection rate reaches more than 90%.Desalting mother liquor returns crystallization kettle, is cooled to 0-5 DEG C, is slowly adjusted with formic acid
PH to 4.3-4.4 is saved, goes out crystalline substance, stops being added dropwise, growing the grain continuously adds formic acid after 2 hours, stop being added dropwise after adjusting pH to 3.6-3.7,
Growing the grain 4 hours again.Then, carry out separation of solid and liquid, obtained cefotaxime crystal once recrystallized again can obtain it is qualified
Product, total recovery now reaches 95.02%.
Embodiment 5：This example demonstrates that implement the situation of present invention process in the equipment of embodiment
Exist with the difference of other embodiment, the film that the embodiment uses is GE companies NF membrane, and model ZK008-2 is through changing
Property is made.After modified, molecular cut off is 200 dalton, Nacl rejections 85%；Modified film feature be to cephalo he
Pyridine rejection is high, good to formates permeability, and resistance tocrocking is good, and easy cleaning regeneration recovers flux.
Take 50kg cefotaximes hydrochloride to be dissolved in 500L pure water in 800L stainless steel cauldrons, 0- is cooled to refrigerant
5 DEG C, mixing speed 80rmin, the pH to 5.5-5.6 of regulation solution is added dropwise with 5N sodium hydroxide solutions, then filters, filter
Liquid is returned to crystallization kettle, is maintained feed temperature slowly to adjust pH to 4.3-4.4 with formic acid at 0-5 DEG C, is gone out crystalline substance, is stopped being added dropwise, is supported
Formic acid is continuously added after brilliant 2 hours, stops being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours.Separation of solid and liquid, mother liquor are collected and beaten
Enter desalter head tank（2）, in tank（2）In crystalline mother solution first with sodium hydroxide solution adjust pH to 4.8-5.0.Mother liquor profit
Carry out desalting processing with membrane separation technique, constantly adjust the pH to 4.3-4.4 of mother liquor with formic acid in desalting processing, behind with pure
Water dilutes desalination, and final salt rejection rate reaches more than 90%.Desalting mother liquor returns crystallization kettle, is cooled to 0-5 DEG C, slow with formic acid
PH to 4.3-4.4 is adjusted, goes out crystalline substance, stops being added dropwise, growing the grain continuously adds formic acid after 2 hours, stop drop after adjusting pH to 3.6-3.7
Add, then growing the grain 4 hours.Then, separation of solid and liquid is carried out, obtained cefotaxime crystal is once recrystallized again to be closed
The product of lattice, total recovery now reach 96.12%.
Claims (7)
- A kind of 1. membrane separating method for recycling ceftazidime mother liquor, it is characterised in that：This method comprises the following steps（1）The temperature of reactor reclaimed water is maintained at 0-5 DEG C, cefotaxime hydrochloride is added, dissolving, sodium hydroxide is added dropwise, adjust PH to 5.5-5.6, filtering, crystallizing tank is transferred to by filtrate；（2）Feed temperature is maintained at 0-5 DEG C, pH to 4.3-4.4 is adjusted with slow acid, goes out crystalline substance, stops being added dropwise, growing the grain is after 2 hours Continuously add acid, stop being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours；（3）Separation of solid and liquid, cefotaxime crystallization yield now is 82%, and the mother liquor after filtering is collected and is transferred to head tank；（4）Crystalline mother solution in head tank adjusts pH to 4.8-5.0 with sodium hydroxide solution；（5）Mother liquor carries out desalination using nano-filtration membrane equipment, and in desalting processing, it is 4.3-4.4 to be adjusted with acid and keep the pH of mother liquor, Adjust the solubility of cefotaxime in mother liquor, and with pure water desalination, until salt rejection rate reach more than 99%；（6）The mother liquor of removing salinity is concentrated using membrane separation technique, and mother liquid concentration is concentrated into more than 6% from 0.5%；（7）Desalting mother liquor is transferred to crystallization kettle, is cooled to 0-5 DEG C, with acid for adjusting pH to 4.3-4.4, goes out crystalline substance, stops being added dropwise, Growing the grain continuously adds acid after 2 hours, stop being added dropwise after adjusting pH to 3.6-3.7, then growing the grain 4 hours；Separation of solid and liquid is carried out, is obtained Cefotaxime crystal, cefotaxime crystal obtain final products through recrystallization.
- 2. according to the method for claim 1, it is characterised in that the acid is formic acid.
- 3. a kind of membrane separation device for recycling ceftazidime mother liquor, it is characterised in that the device contains modular pure water tank （1）, raw material tank arrangement（2）, purge tank（3）, formic acid tank（4）, discharging pump（5）, charging pump（6）, high-pressure pump（7）, circulating pump （8）, cartridge filter（9）, heat exchanger（10）, NF membrane and membrane module（11）, connecting pipeline and Automated condtrol system；Wherein, pure water tank（1）, raw material tank arrangement（2）, purge tank（3）Discharging opening and discharging pump（5）, charging pump（6）UNICOM, supply Expect pump（6）With cartridge filter（9）UNICOM；Formic acid tank（4）With cartridge filter（9）UNICOM；Cartridge filter（9）With heat exchanger （10）UNICOM；Heat exchanger（10）With high-pressure pump（7）；High-pressure pump（7）With circulating pump（8）UNICOM；Circulating pump（8）With NF membrane and film Component（11）Feed inlet end UNICOM；NF membrane and membrane module（11）Discharge port end and pure water tank（1）, raw material tank arrangement（2）, cleaning Tank（3）UNICOM；Wherein, the control device of automation, include the on-line checking and control system of pH value, pass through on-line checking formic acid tank（4） With cartridge filter（9）PH value, and control enter formic acid tank（4）With cartridge filter（9）The folding of outlet valve, realize The On-line Control of pH value；Also flow sensor is provided with including pump（20）~（22）, pressure sensor（14）、（17）、（18）And control Device processed, flow sensor（19）、（20）、（22）The pressure and data on flows imported and exported in pump are gathered with pressure sensor, and is passed Transport to controller（12）、（16）、（21）, data reception module, processing module and communication module, data receiver are provided with controller Module is transferred to processing module after receiving the data message of two sensor transmissions, is finally transmitted again via communication module to service Terminal；Service terminal receives the data message that controller is sent, and is shown in its display screen.
- 4. the method for ceftazidime mother liquor is recycled using the device described in claim 3, it is characterised in that:Mother liquor enters Batch can（2）PH to 4.8-5.0 is adjusted with sodium hydroxide solution afterwards, passes through charging pump（6）, by cartridge filter（9）, then pass through Heat exchanger（10）, the temperature of feed liquid is maintained at 0-5 DEG C, then by high-pressure pump（7）, circulating pump（8）, into NF membrane（11）Carry out Desalination, the salt solution of transmission enter sewerage, circulation fluid feed back tank（2）, the mother liquor after desalination passes through discharging pump（5）Into crystallization Kettle carries out secondary crystallization.
- 5. according to the method for claim 4, it is characterised in that mother liquor is popped one's head in desalination processes by pH（13）, sum Control valve（12）Automatic feedback feed supplement is carried out, by formic acid tank（4）In formic acid add mother liquor in, it is 4.3-4.4 to keep its pH value.
- 6. according to the method for claim 4, it is characterised in that by pure water tank（1）In pure water be supplemented to film filter module, Ensure that pure water supplements in desalination processes, purge tank（3）In water for cleaning injection film filter module, ensureing nanofiltration film module just Often operation.
- 7. according to the method for claim 4, it is characterised in that the film is special membrane, model ZK008-2.
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