CN102532213A - Method for preparing ribostamycin rough products by using membrane separation technology - Google Patents
Method for preparing ribostamycin rough products by using membrane separation technology Download PDFInfo
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- CN102532213A CN102532213A CN2011104497467A CN201110449746A CN102532213A CN 102532213 A CN102532213 A CN 102532213A CN 2011104497467 A CN2011104497467 A CN 2011104497467A CN 201110449746 A CN201110449746 A CN 201110449746A CN 102532213 A CN102532213 A CN 102532213A
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Abstract
The invention provides a method for preparing ribostamycin rough products by using membrane separation technology. The method comprises the steps of micro filter membrane edulcoration of feed liquid, ultrafiltration decoloration and nanofiltration desalination, enrichment, concentration and drying in a preparation process of the ribostamycin rough products. The feed liquid containing ribostamycin is carried out liquid and solid separation of micro filter membrane, protein micro filter permeating liquid, coloring matters, polysaccharide and other macromolecule impurities are removed through the ultrafiltration membrane, collected permeating liquid is desalted and enriched under normal temperature through the permeating liquid, and the desalt liquid is concentrated and dried to manufacture the ribostamycin rough products. The method for preparing ribostamycin rough products by using the membrane separation technology is novel in conception, mild in productive technology conditions, environment-friendly and clean, simple and easy to do, short in production cycle, low in production cost, high in extraction yield and strong in application, and has big application and dissemination values.
Description
Technical field
The present invention relates to a kind of aminoglycoside antibiotics ribostamycin separation of produced method, be specially and relate to a kind of method that adopts membrane separation technique separation of produced ribostamycin.
Background technology
Ribostamycin is a kind of Broad spectrum antibiotics, and is effective to the Bacillus proteus bacterial strain of staphylococcus, suis, streptococcus pneumoniae, pneumobacillus, intestinal bacteria and part.Be applicable to the various severe infections that responsive enterobacteriaceae lactobacteriaceae such as escherichia coli, klebsiella spp, proteus, Shigella etc. cause clinically, like respiratory tract, abdominal cavity, thoracic cavity, urinary tract, skin and soft tissue, osseous tissue and eye, ear, nose infection due to pneumonia, septicemia, biliary tract infection and the responsive gram negative bacillus.Compare with other aminoglycoside antibioticss such as kantlex etc., toxicity is lower, and is all less to the toxicity of the sense of hearing and kidney, is its main advantage.Common many and wide spectrum semi-synthetic penicillins, cephalosporins or other antibacterials combined utilization.
Therefore, develop a kind of ribostamycin separation of produced method of efficient energy-saving, have good market outlook and social benefit.
Ribostamycin is to be that to produce bacterium, W-Gum, soybean cake powder be that main raw material is cultivated the secondary metabolite that obtains through submerged fermentation with actinomycetes.The ribostamycin extraction preparation method mainly adopts plate-and-frame filter press press filtration, filtrating directly to drop into the separation and Extraction that fermented liquid carries out Static Adsorption, realizes ribostamycin through ion exchange resin dynamic adsorption or ion exchange resin at present.
The technology weak point is at present: the dynamic adsorption process, even add flocculating aids, the still more sad filter of fermented liquid in the fermented liquid Plate Filtration process; Filtration velocity is slow; Filter pressure is up to 0.4-0.6Mpa, and filter cake is shapeless, feed liquid is lost, it is on the low side to filter yield, and labour intensity is big; And the Static Adsorption process, ion exchange resin with fermented liquid in the residue sepn process in, situation such as it is serious that ion exchange resin runs off, and the low and contaminated wastewater of yield is more serious.
Summary of the invention
The present invention provides a kind of method that adopts membrane separation technique to prepare the ribostamycin bullion.The ribostamycin fermented liquid is handled through microfiltration membrane, removes a large amount of thalline, bacterial chip, high molecular weight protein and fermented liquid residues in the fermented liquid, obtains the clarification micro-filtration and sees through liquid; Micro-filtration sees through liquid and further removes macromole impurity such as deproteinize, pigment and polysaccharide through ultra-filtration membrane, and the ultrafiltration of collection sees through liquid and carries out normal temperature desalination, enrichment through nf membrane; Demineralised liquid becomes the about 8-15Be of concentration ° liquid concentrator through thin film concentration, supplies further purification production ribostamin or liquid concentrator to make the ribostamycin bullion through centrifugal spray drying and supplies the refining ribostamin of producing.The present invention has alleviated productive labor intensity, has improved the recovery of separation and Extraction, has reduced the quantity discharged of acidic and alkaline waste water.
The concrete parameter and the process characteristic of the microfiltration membrane of the separation and Extraction ribostamycin that the present invention adopts, ultra-filtration membrane, nf membrane are following:
1. select for use molecular weight cut-off to be 30000-500000, preferentially to select the microfiltering separation film of 50000-100000; At the microfiltration membrane flux is 30L/h ㎡～50L/h ㎡, and working pressure is through micro-filtration separation of mycelial, culture medium residue etc. under the operational condition of 5 ℃～35 ℃ of 1.0 bar-3.5bar, service temperature;
2. selecting molecular weight cut-off for use is 5000～100000 ultra-filtration and separation film; At the ultra-filtration membrane flux is 30L/h ㎡～45 L/h ㎡; Working pressure is 1.0 bar～6.0bar; Through the ultrafiltration removal of impurities, remove macromole impurity such as protein, polysaccharide and colour former under the operational condition that service temperature is 5 ℃～35 ℃;
3. it is 300～800 nanofiltration separation membrane that nf membrane desalination, enrichment process are selected molecular weight cut-off for use; It is 20L/h ㎡～40 L/h ㎡ at the nf membrane flux that ultrafiltration sees through liquid; Working pressure is 6.0 bar～12.0bar; Under the operational condition that service temperature is 5 ℃～35 ℃, through nanofiltration desalination, enrichment 3～5 times, the volume of demineralised liquid is about the 20-30% of filtrating;
4. the mould material of microfiltration membrane separating thallus, residue process can be one or more and combination of inorganic ceramic material, metal, alloy and other non-metallic material, preferentially selects stupalith for use;
5. the mould material of ultra-filtration membrane removal of impurities, decolorization can be one or more in inorganic ceramic class, polysulfones, polyvinylidene difluoride, aromatic polyamides class, FM class, the composite package class mould material; Preferentially select composite package class, polysulfones, polyvinylidene difluoride, aromatic polyamides class for use; The membrane module type of said ultra-filtration membrane can be tubular type, tubular fibre, rolling, plate and frame, preferentially selects rolled film for use;
6. the mould material of nanofiltration desalination, concentration process can be one or more in polyvinylidene difluoride, aromatic polyamides class, FM class, the composite package class mould material, preferentially selects composite package class, vinylidene fluoride class, aromatic polyamides class for use; The membrane module type of said nf membrane can be tubular type, rolling, plate and frame, preferentially selects rolled film for use.
Compare with existing Technology, the present invention has outstanding feature:
1. present method not only helps containing feed liquid removal of impurities, separation, desalination, the enrichment of ribostamycin, and has got rid of the required heavy process such as sheet frame operation of dynamic adsorption technology;
2. present method benefit feed liquid of being to avoid Static Adsorption causes in the ribostamycin leaching process resin drift or Plate Filtration to cause caused yield that runs off descends;
3. present method benefit is that technology is simple, the energy consumption material consumption is low, green cleaning, be convenient to implement, and the activity duration is short, reduced add that flocculating aids causes secondary pollution etc., improved the quality of product.
Embodiment
Adopt membrane separation technique to prepare the method for ribostamycin liquid concentrator or ribostamycin bullion in order better to set forth the present invention, below the present invention is described further, but do not limit the present invention in any way through specific embodiment.
Embodiment 1
To contain ribostamycin concentration is that the fermented liquid 260L of 5.5g/L is a raw material, and adopting molecular weight cut-off is 50000 ceramic microfiltration membrane, is 35L/h ㎡ at flux, and working pressure is 2.5bar, removes fermented liquid thalline and residue under the operational condition that service temperature is 35 ℃.Seeing through liquid, to adopt molecular weight cut-off be 5000 composite hyperfiltration membrane, is 30 L/h ㎡ at membrane flux, and working pressure is 5.0bar, through the ultra-filtration membrane removal of impurities, removes protein, polysaccharide and colour former etc. under the operational condition that service temperature is 30 ℃.Ultrafiltration sees through liquid, and to adopt molecular weight cut-off be that 300 composite package carries out nanofiltration and handles; At the nf membrane flux is 30 L/h ㎡; Working pressure is 10.0bar; Under the operational condition that service temperature is 30 ℃, through 3 nanofiltration desalinations, enrichment, demineralised liquid concentrates, is spray dried to ribostamycin off-white color bullion through film under vacuum.Through measuring the ribostamycin recovery is 96.2%, and ribostamycin content is 83.8%.
Embodiment 2
To contain ribostamycin concentration is that the fermented liquid 350L of 5.0g/L is a raw material, and adopting molecular weight cut-off is 50000 ceramic microfiltration membrane, is 40L/h ㎡ at flux, and working pressure is 3.0bar, removes fermented liquid thalline and residue under the operational condition that service temperature is 30 ℃.Seeing through liquid, to adopt molecular weight cut-off be 5000 composite hyperfiltration membrane, is 30 L/h ㎡ at membrane flux, and working pressure is 5.0bar, through the ultra-filtration membrane removal of impurities, removes protein, polysaccharide and colour former etc. under the operational condition that service temperature is 30 ℃.Ultrafiltration sees through liquid, and to adopt molecular weight cut-off be that 300 composite package carries out nanofiltration and handles; At the nf membrane flux is 30 L/h ㎡; Working pressure is 8.0bar; Under the operational condition that service temperature is 30 ℃, through 4 nanofiltration desalinations, enrichment, demineralised liquid concentrates, is spray dried to ribostamycin off-white color bullion through film under vacuum.Through measuring the ribostamycin recovery is 94.6%, and ribostamycin content is 80.2%.
Embodiment 3
To contain ribostamycin concentration is that prostitute's mother liquor 35L of 98.0g/L is a raw material; Purified water is diluted to 350L, and to adopt molecular weight cut-off be 50000 ceramic microfiltration membrane; At flux is 40L h ㎡, and working pressure is 3.0bar, removes mother liquor impurity under the operational condition that service temperature is 30 ℃.Seeing through liquid, to adopt molecular weight cut-off be 5000 composite hyperfiltration membrane, is 30 L/h ㎡ at membrane flux, and working pressure is 5.0bar, through the ultra-filtration membrane removal of impurities, removes colour former etc. under the operational condition that service temperature is 30 ℃.Ultrafiltration sees through liquid, and to adopt molecular weight cut-off be that 300 composite package carries out nanofiltration and handles; At the nf membrane flux is 30 L/h ㎡; Working pressure is 10.0bar; Under the operational condition that service temperature is 30 ℃, through 5 nanofiltration desalinations, enrichment, demineralised liquid concentrates, is spray dried to ribostamycin off-white color bullion through film under vacuum.Through measuring the ribostamycin recovery is 96.8%, and ribostamycin content is 82.5%.
Claims (10)
1. method that adopts membrane separation technique to prepare the ribostamycin bullion; Be primarily characterized in that and comprise microfiltration membrane removal mycelium, fermented liquid residue; Ultra-filtration membrane removal of impurities, decolouring and nf membrane desalination, enrichment; Concentrated, exsiccant step: the feed liquid that contains ribostamycin is handled through microfiltration membrane, removes mycelium, fermented liquid residue; Micro-filtration sees through liquid and removes macromole impurity such as protein, pigment and polysaccharide through ultra-filtration membrane; The ultrafiltration of collecting sees through liquid and carries out normal temperature desalination, enrichment through nf membrane, and demineralised liquid makes the ribostamycin bullion through concentrated, drying.
2. a kind of method that adopts membrane separation technique to prepare the ribostamycin bullion according to claim 1; It is characterized in that: with the feed liquid that contains ribostamycin is raw material; Under the working pressure of 1.5-3.5bar, remove impurity such as mycelium, culture medium residue through microfiltration membrane; Microfiltration membrane sees through liquid under 1.5～6.0bar working pressure condition, through macromole impurity such as ultra-filtration membrane decolouring, removal protein and polysaccharide; Ultrafiltration membrane permeate liquid is under 6.0～12bar working pressure condition, through nf membrane desalination, enrichment; Demineralised liquid is through concentrated, the dry ribostamycin bullion that obtains.
3. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: it is the separatory membrane of 30000-500000 that said microfiltration membrane separating thallus, residue process are selected molecular weight cut-off for use; It is 5000～30000 separatory membrane that ultra-filtration membrane removal of impurities process is selected molecular weight cut-off for use; It is 300～800 separatory membrane that nf membrane desalination, enrichment process are selected molecular weight cut-off for use.
4. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: the mould material of said microfiltration membrane separating thallus, residue process is one or more and combination of inorganic ceramic material, metal, alloy and other non-metallic material.
5. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: the mould material of macromole impurity processes such as ultra-filtration membrane decolouring, removal protein and polysaccharide is one or more in inorganic (containing stupalith, metal, alloy and other non-metallic material) class, polysulfones, polyvinylidene difluoride, aromatic polyamides class, FM class, the composite package class mould material.
6. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: the mould material in said nf membrane desalination, the concentration process is one or more in polyvinylidene difluoride, aromatic polyamides class, FM class, the composite package class mould material.
7. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: the membrane module type of said microfiltration membrane, ultra-filtration membrane, nf membrane is one or more in tubular type, tubular fibre, rolling, the plate and frame.
8. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: the membrane flux that said microfiltration membrane is removed thalline, residue process is 30-50L/h ㎡, 5 ℃～35 ℃ of service temperatures; The membrane flux of ultra-filtration membrane decolouring, removal of impurities process is 30L/h ㎡～45 L/h ㎡, 5 ℃～35 ℃ of service temperatures; The membrane flux of nf membrane desalination, enrichment process is 20L/h ㎡～40 L/h ㎡, 5 ℃～35 ℃ of service temperatures.
9. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: said feed liquid is the fermented liquid that contains the ribostamycin composition, ferment filtrate, liquid concentrator, sees through liquid, crystalline mother solution, recovery liquid etc.
10. employing membrane separation technique according to claim 1 prepares the method for ribostamycin bullion, it is characterized in that: said ribostamycin bullion is to contain the liquid liquid concentrator of ribostamycin content >=70%, solid-state bullion etc.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106554374A (en) * | 2016-11-29 | 2017-04-05 | 无锡福祈制药有限公司 | A kind of method that purification prepares vistamycin in fermentation liquid from ribostamycin |
| CN108148100A (en) * | 2017-09-15 | 2018-06-12 | 江苏九天高科技股份有限公司 | The method of purification and device of a kind of oligosaccharide |
| CN110272461A (en) * | 2019-06-29 | 2019-09-24 | 赤峰蒙广生物科技有限公司 | A method of purifying beta-thymidine from fermentation liquid |
| CN111004298A (en) * | 2019-12-20 | 2020-04-14 | 无锡福祈制药有限公司 | Preparation method of high-purity ribostamycin sulfate |
| CN112851721A (en) * | 2021-01-21 | 2021-05-28 | 浙江新银象生物工程有限公司 | Method for recovering natamycin crystallization mother liquor |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106554374A (en) * | 2016-11-29 | 2017-04-05 | 无锡福祈制药有限公司 | A kind of method that purification prepares vistamycin in fermentation liquid from ribostamycin |
| CN106554374B (en) * | 2016-11-29 | 2018-11-27 | 无锡福祈制药有限公司 | A method of purification prepares vistamycin from ribostamycin fermentation liquid |
| CN108148100A (en) * | 2017-09-15 | 2018-06-12 | 江苏九天高科技股份有限公司 | The method of purification and device of a kind of oligosaccharide |
| CN108148100B (en) * | 2017-09-15 | 2023-06-06 | 江苏九天高科技股份有限公司 | Method and device for purifying oligosaccharide |
| CN110272461A (en) * | 2019-06-29 | 2019-09-24 | 赤峰蒙广生物科技有限公司 | A method of purifying beta-thymidine from fermentation liquid |
| CN110272461B (en) * | 2019-06-29 | 2022-09-06 | 赤峰蒙广生物科技有限公司 | Method for purifying beta-thymidine from fermentation liquor |
| CN111004298A (en) * | 2019-12-20 | 2020-04-14 | 无锡福祈制药有限公司 | Preparation method of high-purity ribostamycin sulfate |
| CN112851721A (en) * | 2021-01-21 | 2021-05-28 | 浙江新银象生物工程有限公司 | Method for recovering natamycin crystallization mother liquor |
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Application publication date: 20120704 |