CN103537192A - Membrane integration device for purifying and concentrating Ertapenem aqueous solution - Google Patents
Membrane integration device for purifying and concentrating Ertapenem aqueous solution Download PDFInfo
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- CN103537192A CN103537192A CN201310511955.9A CN201310511955A CN103537192A CN 103537192 A CN103537192 A CN 103537192A CN 201310511955 A CN201310511955 A CN 201310511955A CN 103537192 A CN103537192 A CN 103537192A
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Abstract
The invention discloses a membrane integration device for purifying and concentrating an Ertapenem aqueous solution. The device mainly comprises an ultra-filtration part, a nano-filtration part and an air inlet and outlet system, wherein the ultra-filtration part mainly comprises a raw material tank (1) with a temperature control system, a low-pressure pump (5), an ultra-filtration membrane component (8) and the like; the nano-filtration part mainly comprises a produced material tank (10), a high-pressure pump (12), a nano-filtration component (16) and the like; a nano-filtration membrane is a hollow fiber nano-filtration membrane, a roll type nano-filtration membrane or a tubular nano-filtration membrane; the air inlet and outlet system comprises a dried air inlet and a dried air outlet, and is used for blowing the membrane components and a pipeline through compressed gas after purification of a material solution is completed so as to reduce the residue of the material solution.
Description
Affiliated technical field: the present invention relates to a kind of antibiotic method of purification, be specially ultrafiltration-NF membrane integrating device of a kind of purification, the concentrated ertapenem aqueous solution.
Background technology: ertapenem is the New-type wide-spectrum carbapenem antibiotic of Merck drugmaker exploitation, obtains US and European respectively at calendar year 2001 and 2002 and ratifies clinical practice, and China is in 2005 approval clinical practices.Ertapenem has has a broad antifungal spectrum, long half time, adds the characteristics such as infringement is little, drug susceptibility is high, tissue permeability good, intramuscular injection bioavilability height.Meanwhile, have good pharmacokinetic properties, the moderate and severe infection that can effectively cause for bacterium multidrug resistant, is considered to the anti-infectious important defence line of the mankind.Therefore, ertapenem is a rising tribactams, for treatment Community Acquired Infections, has fabulous efficacy and saferry.Along with bacterial resistance problem is increasingly severe, the demand of ertapenem is increasing.
In the production of ertapenem, how from synthetic liquid, generated ertapenem being purified and to be concentrated, is the difficult point that ertapenem is produced.In synthetic liquid, the mass concentration of ertapenem is only 0.5%-3%, and concentration is lower; And purge process is harsh, and treatment temperature is lower than 15 ℃, and pH value stabilization is at 4.5-5.8, and the processing time is more short better.
The method of purification ertapenem mainly contains solvent extraction, reduced pressure concentration and column chromatography purification etc. at present, but all there is certain problem in these methods: (1) solvent extraction method needs a large amount of solvents (extractant, washing agent etc.), and the recovery of solvent needs complicated technique (rectifying, evaporation etc.); Product design is low, have dissolvent residual, purifying cost is high, yield is low; (2) reduced pressure concentration method has higher requirement to retort material and sealing, and this method is carried out under certain temperature and vacuum, and energy consumption is high, pollution is heavy, and material is all concentrated, and product purity is not high; (3) column chromatography relates to the problems such as silica gel chromatography or preparative chromatography recovery, is difficult to industrialization.In a word, these method of purification techniques are loaded down with trivial details, purification efficiency ground, and product purity, concentration are all low; In addition, residual ertapenem and organic solvent are difficult to recycle, and not only environment are caused to severe contamination, also bring about great losses economically.
Summary of the invention
The invention provides the film integrating device of a kind of purification, the concentrated ertapenem aqueous solution.This device mainly comprises: ultrafiltration part, nanofiltration part and air inlet exhaust system.Ultrafiltration part mainly comprises: with the head tank 1 of temperature-controlling system, low-lift pump 5, hyperfiltration membrane assembly 8 etc.; Described nanofiltration part mainly comprises produces batch can 10, high-pressure pump 12 and nanofiltration assembly 16 etc.; Described air inlet exhaust system comprises dry air air inlet and floss hole,
After having purified for feed liquid, utilize Compressed Gas to purge membrane module and pipeline, reduce feed liquid residual.
Wherein, partial devices technological parameter of the present invention is as follows:
The temperature-controlling system of head tank is refrigerant or other cooling systems, guarantees that the temperature of the ertapenem aqueous solution is between 0-15 ℃; Described milipore filter is the milipore filter of the materials such as polysulfones, polyether sulfone, Kynoar and polyacrylonitrile, and its molecular cut off is 1000-300000, and operating pressure is 0-3MPa, and operating temperature is 0-15 ℃.The temperature-controlling system that produces batch can is refrigerant or other cooling systems, guarantees that the temperature of the ertapenem aqueous solution is between 0-15 ℃; Described NF membrane is doughnut, tubular type or rolling NF membrane, the rejection that is 0-30% ertapenem to mass concentration is 99.8%, to hydrogen ion and hydroxide ion, without holding back, nanofiltration part operation pressure is 0.2-1.5MPa, and operating temperature is 0-15 ℃.The pH value of whole process concentrate is 4.5-5.8, and the processing time is 0.5h-3h.
The technical process of device of the present invention is:
The synthetic liquid of ertapenem is added in head tank 1, synthetic liquid through milipore filter filter out impurities, large molecule etc., enter and produce in batch can 10; Feed liquid after ultrafiltration enters nanofiltration membrane component after by high-pressure pump supercharging, and ertapenem is held back by NF membrane, is back to and produces in batch can 10; Concentrate is circulated to after the cycles of concentration of regulation, by producing batch can discharge gate 11, discharges; See through in liquid and contain unreacted monomer, water and part hydrogen ion, via seeing through liquid outlet 17, discharge, recycling after reclaiming.In circulation concentration process, concentrate pH value remains unchanged.After concentration process finishes, available air inlet exhaust system purges whole system, and in reduction system, material is residual.
Ertapenem of the present invention is purified, the technical advantage of enrichment facility is as follows:
1. ultra-filtration process has been removed the impurity such as large molecule in raw material; Nanofiltration process is realized and is selected separation, and the rejection of the ertapenem aqueous solution that is 0-30% to mass concentration approaches 100%, and unreacted small molecule monomer, hydrogen ion and solvent are not held back substantially; In purifying, concentration process, pH value stabilization is at 5.6-5.8.After two-stage membrane filtration, feed liquid is purified, and ertapenem is concentrated, and can obtain mass concentration and be 30% the pure ertapenem aqueous solution of high concentration.
2. see through the recyclable recycling of liquid, cost-savingly do not produce environmental pollution.
3. purify, be concentrated in nanofiltration section and complete simultaneously, technique is simple, low temperature can operate, without adding, without phase transformation.
4. purify, concentrated speed is fast, the time is short, the conventional 1-3 hour that foreshortens to for 1-2 days.
Accompanying drawing explanation
Fig. 1 is that ertapenem of the present invention is purified, the structural representation of enrichment facility.Details are as follows for device each several part:
1. head tank; 2. air bleeding valve; 3. thermometer 1; 4. head tank discharge gate; 5. centrifugal pump; 6. valve 1; 7. Pressure gauge 1; 8. hyperfiltration membrane assembly; 9. microfiltration systems exhaust outlet; 10. produce batch can; 11. produce batch can discharge gate; 12. high-pressure pumps; 13. valves 2; 14. Pressure gauges 2; 15. nanofiltration system exhaust outlets; 16. nanofiltration membrane components; 17. see through liquid outlet; 18. nanofiltration system air inlets; 19. valves 3; 20. thermometers 2; 21. valves 4; 22. microfiltration systems air inlets; 23. valves 5.
The specific embodiment
Below in conjunction with embodiment and further narration the present invention of accompanying drawing 1, these specific embodiments, only for further narration the present invention, do not limit the protection domain of the present patent application claim.
Embodiment 1
Design one and utilize nanofiltration purification ertapenem antibiotic device, the milipore filter of described device is polyvinylidene fluoride hollow fiber microfiltration membranes, and molecular cut off is 1000; NF membrane is doughnut, tubular type or rolling NF membrane; Refrigerant is liquid nitrogen; Air inlet connects air compressor.
It is 5 ℃ that head tank 1 temperature is controlled, and the synthetic liquid 20Kg of ertapenem that reaction is completed adds in head tank 1, and wherein synthetic liquid be take 4R-hydroxyl-L-PROLINE as initiation material (content 935.5g, 7.11mol).Open low-lift pump 5, operating pressure is 0.1MPa, and synthetic liquid filters through hyperfiltration membrane assembly 8, sees through liquid and enters in product batch can 10.Air compressor is accessed to air inlet 22, purge, residue adds and produces in batch can 10 after reclaiming.Producing batch can 10 temperature controls is 5 ℃, and after 12 superchargings of unlatching high-pressure pump, feed liquid enters nanofiltration membrane component 16, and control operating pressure is 1.5MPa, and pH value is 4.5, sees through liquid collection and recycles, and concentrate cycles back in product batch can 10, purifies complete after 1.0h.Air compressor is connected with air inlet 18, opens discharge gate 15 and discharge concentrate.In concentrate, add 10L ethanol, be cooled to 0 ℃, growing the grain 1.5h filters, and ethanol (1L) washing leaching cake is drained final vacuum and within dry 2 hours, obtained white crystal 3.11Kg, and productive rate 92%, detects purity 99%.
Embodiment 2
Design one and utilize nanofiltration purification ertapenem antibiotic device, the milipore filter of described device is polysulfone hollow fibre microfiltration membranes, and molecular cut off is 1000; NF membrane is doughnut, tubular type or rolling NF membrane; Refrigerant is liquid nitrogen; Air inlet connects air compressor.
It is 5 ℃ that head tank 1 temperature is controlled, and the synthetic liquid 15Kg of ertapenem that reaction is completed adds in head tank 1, and wherein N-(O, O-diisopropyl phosphoryl)-trans-CHP content is 1.568Kg (5.332mol).Open low-lift pump 5, operating pressure is 0.3MPa, and synthetic liquid filters through hyperfiltration membrane assembly 8, sees through liquid and enters in product batch can 10.Air compressor is accessed to air inlet 22, purge, residue adds and produces in batch can 10 after reclaiming.Producing batch can 10 temperature controls is 10 ℃, and after 12 superchargings of unlatching high-pressure pump, feed liquid enters nanofiltration membrane component 16, and control operating pressure is 0.5MPa, and pH value is 5.6, sees through liquid collection and recycles, and concentrate cycles back in product batch can 10, purifies complete after 1.0h.Air compressor is connected with air inlet 18, opens discharge gate 15 and discharge concentrate.In concentrate, add 8L toluene, be cooled to 2 ℃ of crystallizatioies, suction filtration, drains final vacuum and is dried to obtain white crystal 2.28Kg, and productive rate 90%, detects purity 98%.
Claims (6)
1. the film integrating device of a purification, the concentrated ertapenem aqueous solution.The invention provides a kind of hollow-fibre membrane continuous coating device, it is characterized in that this device mainly comprises: ultrafiltration part, nanofiltration part and air inlet exhaust system.Ultrafiltration part mainly comprises: with the head tank 1 of temperature-controlling system, low-lift pump 5, hyperfiltration membrane assembly 8 etc.; Described nanofiltration part mainly comprises produces batch can 10, high-pressure pump 12 and nanofiltration assembly 16 etc.; Described NF membrane is hollow fiber nanofiltration membrane, rolling NF membrane or tubular type NF membrane; Described air inlet exhaust system comprises dry air air inlet and floss hole, utilizes Compressed Gas to purge membrane module and pipeline for feed liquid after having purified, and reduces feed liquid residual.
2. according to claim 1, its feature is refrigerant or other cooling systems at the temperature-controlling system with head tank, guarantees that the temperature of the ertapenem aqueous solution is between 0-15 ℃.
3. according to claim 1, described milipore filter is the milipore filter of the materials such as polysulfones, polyether sulfone, Kynoar and polyacrylonitrile, and its molecular cut off is 1000-300000, and operating pressure is 0-3MPa, and operating temperature is 0-15 ℃.
4. according to claim 1, the temperature-controlling system that produces batch can is refrigerant or other cooling systems, guarantees that the temperature of the ertapenem aqueous solution is between 0-15 ℃.
5. according to claim 1, described NF membrane is doughnut or rolling NF membrane, and the rejection that is 0-30% ertapenem to mass concentration is 99.8%, to hydrogen ion and hydroxide ion without holding back, nanofiltration part operation pressure is 0.2-1.5MPa, and operating temperature is 0-15 ℃.
6. according to claim 1, in purification, concentration process, the pH value of concentrate is 4.5-5.8, and the processing time is 0.5h-3h.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109012195A (en) * | 2018-09-20 | 2018-12-18 | 佛山市海天（江苏）调味食品有限公司 | A kind of ultrafiltration system and its operating method |
| CN112370971A (en) * | 2020-09-22 | 2021-02-19 | 山东大溪环保科技发展有限公司 | Separation and concentration method and separation and concentration device for food materials |
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| CN112370971A (en) * | 2020-09-22 | 2021-02-19 | 山东大溪环保科技发展有限公司 | Separation and concentration method and separation and concentration device for food materials |
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Application publication date: 20140129 |