CN106039283A - Preparation method of colistin sulfate premix - Google Patents
Preparation method of colistin sulfate premix Download PDFInfo
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- CN106039283A CN106039283A CN201610713969.2A CN201610713969A CN106039283A CN 106039283 A CN106039283 A CN 106039283A CN 201610713969 A CN201610713969 A CN 201610713969A CN 106039283 A CN106039283 A CN 106039283A
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Abstract
The invention relates to a preparation method of a colistin sulfate premix, successively comprising the following steps: fermentation, pretreatment of a fermentation broth, filtration, ultrafiltration, first concentration, secondary concentration, and drying. The technology is simple; yield is high; and cost is low. The whole technological process is a physical separation process, and no organic solvent is adopted. Thus, pollutants are greatly reduced. In addition, energy conservation and consumption reduction are realized. The prepared colistin sulfate premix has stable quality, good storage stability and good using effect.
Description
Technical field
The present invention relates to the preparation method of a kind of colistine sulfate pre-mixing agent.
Background technology
Colistin sulfate pre-mixing agent is that colistin sulfate is formulated with the carrier such as Testa oryzae, precipitated calcium carbonate.Sulphuric acid Acarasiales
Element is basic polypeptide class antibiotic, is mainly used in the infection of poultry preventing and treating sensitive organism, and its mechanism of action is that first absorption antibacterial is thin
Born of the same parents' ancient piece of jade, round, flat and with a hole in its centre, in conjunction with the free phosphorus hydrochlorate of lipoprotein in cell membrane so that surface of cell membrane tension force reduces, permeability increases, and causes born of the same parents
Slurry outflow, cell death.
From fermentation liquid, separate colistine sulfate at present mainly have: ion exchange, alkaline precipitation, foamet.
A large amount of waste water, serious environment pollution, spray drying is brought to cause when Strong acid ion-exchanger step length, ion exchange resin regeneration
Steam consumption is big.Alkaline precipitation precipitation separation in course of industrialization is extremely difficult, yield is low, produce pungent ammonia odor simultaneously
Road, site environment is poor, and commercial production operability is not strong, is only suitable for experimental research.Foamet bubbles and uses solvent,
Cause environment pollution, and yield is low, relatively costly.As disclosed in patent CN100347188C, a kind of foamet, needs
Add the organic solvents such as ethanol, acetone, ether, cause environment pollution.And patent CN103059105B discloses a kind of sulphuric acid
The extracting method of colistin, this method increases nanofiltration enrichment process, but this nanofiltration enrichment process is the base in ion exchange
Carry out on plinth, it is impossible to avoid the ion exchange a large amount of waste water consuming in a large number and bringing to soda acid, and the method needs
Repeatedly material being carried out pH regulator, technique is relatively complicated.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of colistine sulfate pre-mixing agent.
The above-mentioned technical purpose of the present invention has the technical scheme that
A kind of preparation method of colistine sulfate pre-mixing agent, its feature comprises the following steps successively:
A. fermentation: by cultivating through one-level kind bottle after elder generation, two grades of kind bottles are cultivated, poly-viscosity bacillus culture fluid after seed tank culture moves
Plant and carry out fermentation culture to fermentation tank, obtain colistine sulfate fermentation liquid.
B. the pretreatment of fermentation liquid: colistine sulfate fermentation liquid sulphuric acid fermentation obtained adjusts pH to 2-6；
C. filter: the colistine sulfate fermentation liquid ceramic membrane filter of pH will be mixed up, and obtain the first filtrate；
D. ultrafiltration: described first filtrate is carried out ultrafiltration with the ultrafilter membrane retaining macromolecule, obtains the second filtrate；
E. first concentrate: described second filtrate is concentrated by ultrafiltration with the ultrafilter membrane retaining small-molecular-weight, obtains the first concentration
Liquid；
F. second concentrate: described first concentrated solution concentrator is concentrated, obtains the second concentrated solution；
G. it is dried: add carrier to the second concentrated solution and stir, and prepare colistine sulfate pre-mixing agent by pneumatic conveying drying.
The problem existed for prior art, the preparation method of the offer of the present invention obtains colistine sulfate by fermentation
Fermentation liquid, first removes the thalline in fermentation liquid with ceramic membrane filter, then removes in filtrate with the ultrafilter membrane retaining macromolecule
Macromolecule impurity, then with the ultrafilter membrane retaining small component, material is concentrated, remove small-molecular-weight impurity simultaneously, then pass through
Concentrate and material is concentrated to higher concentration, finally material mixed homogeneously with carrier and prepare sulphuric acid Bacillus adhaerens by pneumatic conveying drying
Element pre-mixing agent.The method technique is simple, yield is high, low cost, and whole technical process is all a physically separate process, does not use organic
Solvent, is greatly decreased the generation of pollution, and the method achieves energy-saving and cost-reducing.
As preferably, the sulphuric acid of the colistine sulfate fermentation liquid described in step b adjusts pH to 2.5-4.
Colistine sulfate is unstable in the environment of pH ＞ 6 or pH ＜ 2, and inventor finds not only may be used by the regulation of pH
To guarantee stablizing of colistine sulfate in time, and without again regulating pH in the subsequent step of the preparation method of the present invention.
Inventor furthermore, it was found that described colistine sulfate fermentation liquid sulphuric acid is adjusted after pH to 2.5-4, follow-up ceramic membrane filter
Speed, efficiency is higher.
As preferably, the ultrafilter membrane retaining macromolecule described in step d, its molecular cut off is 5000-20000 dongle
?.
Owing to colistine sulfate fermentation liquid containing substantial amounts of hmw protein, will with the ultrafilter membrane retaining macromole
It is removed, and inventor further finds to protect the follow-up ultrafilter membrane retaining little molecule through step d, prevents macromolecule
Albumen is blocked, and can also improve the cycles of concentration of subsequent step e simultaneously, and then reduce the energy consumption of subsequent step f.
As preferably, the ultrafilter membrane retaining macromolecule described in step d, its molecular cut off is 8000-15000 dongle
?.
Inventor finds that the molecular cut off of ultrafilter membrane described in step d is too small, and described colistine sulfate fermentation liquor walks
After rapid d, more colistine sulfate can be made to be retained by ultrafilter membrane, cause the reduction of yield；Molecular cut off is excessive, described sulfur
In acid colistin fermentation liquid, more polymer substance cannot be trapped, and then reduces the thickening efficiency of subsequent step e, even
Cause ultrafilter membrane in step e blocked or cannot be carried out being concentrated by ultrafiltration.
As preferably, the ultrafilter membrane retaining small-molecular-weight described in step e, its molecular cut off is 500-1500 dongle
?.
Owing to the molecular weight of colistine sulfate is relatively big, it is possible not only to remove little molecule by retaining the ultrafilter membrane of little molecule
The impurity of amount, it is often more important that can be concentrated by colistine sulfate material, reduces the steam consumption of subsequent concentration equipment, it is achieved joint
Can consumption reduction.
As preferably, the ultrafilter membrane retaining small-molecular-weight described in step e, its molecular cut off is 500-1200 dongle
?.
Inventor finds that the ultrafilter membrane molecular cut off described in step e is excessive, has the sulfur that moieties amount is relatively small
Acid colistin runs off through ultrafilter membrane, causes the reduction of yield.
As preferably, the concentrator described in step f is in plate-type evaporator, Three-effect concentration device, MVR vaporizer
Kind.
Compared with traditional concentrator, described plate-type evaporator, Three-effect concentration device, MVR vaporizer can reduce steam
Consume.Inventor finds, the ultrafiltration concentration described in integrating step e, energy conservation and consumption reduction effects of the present invention is notable.
As preferably, the carrier described in step g is in defatted rice bran, precipitated calcium carbonate, maize cob meal, wheat bran, zeolite powder
One or more.
Described carrier moisture content is low, rough surface, absorption affinity strong, stable chemical nature, capacity are suitable, and inventor finds described
Carrier and described second concentrated solution mixing the pre-mixing agent stay in grade of preparation, shelf-stable after drying.
As preferably, the temperature cultivated with two grades of kind bottles cultivated by the one-level kind bottle described in step a is 27-31.5 DEG C, stirring
Rotating speed is 200-240rpm, incubation time is 20-28h, and the temperature of described seed tank culture is 29.5-33.5 DEG C, stirring turn
Speed is 75-85m for 70-90rpm, ventilation3/ h, tank pressure are 0.02-0.03Mpa, pH value is 5.0-7.5, and cultivation cycle is 18-
30h, the temperature of described fermentation culture is 29.5-33.5 DEG C, speed of agitator is 60-100rpm, ventilation is 1:0.35-
0.55, tank pressure be 0.02-0.03Mpa, pH value be 5.8-6.0.
Fermentation liquid is the basis preparing colistine sulfate pre-mixing agent, and inventor finds, by step a of the present invention and preferably
The technological parameter colistine sulfate fermentation liquid that obtains of fermentation in colistine sulfate content is high, molecular weight and sulphuric acid Bacillus adhaerens
The impurity that element molecular weight is close is less, is especially suitable for the carrying out of subsequent step of the present invention.
As preferably, it is 10%-20% that step g prepares colistine sulfate pre-mixing agent content.
Inventor finds, the colistine sulfate that content is 10%-20% prepared by the preparation method of the present invention is premixed
Agent stay in grade, shelf-stable, using effect is good simultaneously.
In sum, the method have the advantages that
The preparation method of a kind of colistine sulfate pre-mixing agent of the present invention, solves the deficiencies in the prior art, and technique is simple, receipts
Rate is high, low cost, and whole technical process is all a physically separate process, does not use organic solvent, and the product of pollution is greatly decreased
Raw, and present invention achieves energy-saving and cost-reducing.
Colistine sulfate pre-mixing agent stay in grade prepared by the present invention, shelf-stable, using effect is good simultaneously.
Accompanying drawing explanation
Fig. 1 is the process chart of the present invention.
Detailed description of the invention
This specific embodiment is only explanation of the invention, and it is not limitation of the present invention, people in the art
The present embodiment can be made after reading this specification by member as required does not has the amendment of creative contribution, but as long as at this
All protected by Patent Law in the right of invention.
Embodiment 1
By cultivating through one-level kind bottle after elder generation, two grades of kind bottles are cultivated, poly-viscosity bacillus culture fluid subcultivation after seed tank culture is to fermentation
Tank carries out fermentation culture, obtains colistine sulfate fermentation liquid.The temperature cultivated with two grades of kind bottles cultivated by described one-level kind bottle
Degree is 27 DEG C, speed of agitator is 200rpm, incubation time is 20h, and the temperature of described seed tank culture is 29.5 DEG C, stirring turns
Speed is 85m for 70rpm, ventilation3/ h, tank pressure are 0.03Mpa, pH value is 5.0, and cultivation cycle is 30h, described fermentation culture
Temperature be 29.5 DEG C, speed of agitator be 60rpm, ventilation be 1:0.55, tank pressure be 0.03Mpa, pH value be 5.8.
Squeeze in storage tank after 60 tons of fermentation liquids of sulfur acid colistin are put tank, add concentrated sulphuric acid while stirring by it
PH value is adjusted to 2.0, is transported in ceramic membrane equipment filter by the fermentation liquid mixing up pH with dnockout pump, collects pottery after waiting pH stable
Membrane filtration liquid.The ceramic membrane filtrate of collection is carried out ultrafiltration with the ultrafilter membrane of molecular cut off 5000, removes the impurity of macromole.Again
Filtrate after ultrafiltration is concentrated with the ultrafilter membrane of molecular cut off 500, removes the impurity of little molecule simultaneously.Finally by ultrafiltration
Concentrated solution after membrance concentration is squeezed in Three-effect concentration device, obtains colistine sulfate concentrated solution 6.0 tons after concentration, adds 8.2 tons
Defatted rice bran, stirring and evenly mixing also passes through pneumatic conveying drying, and final prepared content is the colistine sulfate pre-mixing agent of 10%.
Embodiment 2
By cultivating through one-level kind bottle after elder generation, two grades of kind bottles are cultivated, poly-viscosity bacillus culture fluid subcultivation after seed tank culture is to fermentation
Tank carries out fermentation culture, obtains colistine sulfate fermentation liquid.The temperature cultivated with two grades of kind bottles cultivated by described one-level kind bottle
Degree is 31.5 DEG C, speed of agitator is 240rpm, incubation time is 28h, and the temperature of described seed tank culture is 33.5 DEG C, stirring
Rotating speed is 90rpm, ventilation is 75m3/ h, tank pressure are 0.02Mpa, pH value is 7.5, and cultivation cycle is 18h, described fermentation training
The temperature supported is 33.5 DEG C, speed of agitator is 100rpm, ventilation is 1:0.35, tank pressure is 0.02Mpa, pH value is 6.0.
Squeeze in storage tank after 60 tons of fermentation liquids of sulfur acid colistin are put tank, add concentrated sulphuric acid while stirring by it
PH value is adjusted to 2.8, is transported in ceramic membrane equipment filter by the fermentation liquid mixing up pH with dnockout pump, collects pottery after waiting pH stable
Membrane filtration liquid.The ceramic membrane filtrate of collection is carried out ultrafiltration with the ultrafilter membrane of molecular cut off 10000, removes the impurity of macromole.
Again the filtrate after ultrafiltration is concentrated with the ultrafilter membrane of molecular cut off 1500, remove the impurity of little molecule simultaneously.Finally will
Concentrated solution after ultrafilter membrane concentrates is squeezed in plate-type evaporator, obtains colistine sulfate concentrated solution 5.5 tons after concentration, adds
3.0 tons of precipitated calcium carbonates, stirring and evenly mixing also passes through pneumatic conveying drying, and final prepared content is the colistine sulfate pre-mixing agent of 20%.
Embodiment 3
By cultivating through one-level kind bottle after elder generation, two grades of kind bottles are cultivated, poly-viscosity bacillus culture fluid subcultivation after seed tank culture is to fermentation
Tank carries out fermentation culture, obtains colistine sulfate fermentation liquid.The temperature cultivated with two grades of kind bottles cultivated by described one-level kind bottle
Degree is 29 DEG C, speed of agitator is 220rpm, incubation time is 24h, and the temperature of described seed tank culture is 31.5 DEG C, stirring turns
Speed is 80m for 80rpm, ventilation3/ h, tank pressure are 0.025Mpa, pH value is 6.0, and cultivation cycle is 24h, described fermentation training
The temperature supported is 31.5 DEG C, speed of agitator is 80rpm, ventilation is 1:0.45, tank pressure is 0.025Mpa, pH value is 5.9.
Squeeze in storage tank after 60 tons of fermentation liquids of sulfur acid colistin are put tank, add concentrated sulphuric acid while stirring by it
PH value is adjusted to 4.0, is transported in ceramic membrane equipment filter by the fermentation liquid mixing up pH with dnockout pump, collects pottery after waiting pH stable
Membrane filtration liquid.The ceramic membrane filtrate of collection is carried out ultrafiltration with the ultrafilter membrane of molecular cut off 10000, removes the impurity of macromole.
Again the filtrate after ultrafiltration is concentrated with the ultrafilter membrane of molecular cut off 800, remove the impurity of little molecule simultaneously.Finally will be super
Concentrated solution after filter membrane concentrates is squeezed in Three-effect concentration device, obtains colistine sulfate concentrated solution 6.1 tons after concentration, adds 3.2
Ton defatted rice bran, stirring and evenly mixing also passes through pneumatic conveying drying, and final prepared content is the colistine sulfate pre-mixing agent of 20%.
Embodiment 4
Embodiment 2 fermentation is used to obtain colistine sulfate fermentation liquid, after 60 tons of fermentation liquids of sulfur acid colistin are put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.2, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 15000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is entered with the ultrafilter membrane of molecular cut off 1200
Row concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in MVR vaporizer, after concentration
Obtaining colistine sulfate concentrated solution 6.4 tons, add 7.8 tons of maize cob meals, stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares
Content is the colistine sulfate pre-mixing agent of 10%.
Embodiment 5
Embodiment 1 fermentation is used to obtain colistine sulfate fermentation liquid, after 60 tons of fermentation liquids of sulfur acid colistin are put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.5, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 8000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is entered with the ultrafilter membrane of molecular cut off 1000
Row concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, after concentration
Obtaining colistine sulfate concentrated solution 5.9 tons, add 3.4 tons of wheat brans, stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares content
It it is the colistine sulfate pre-mixing agent of 20%.
Embodiment 6
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after 60 tons of fermentation liquids of sulfur acid colistin are put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.3, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 10000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is carried out with the ultrafilter membrane of molecular cut off 800
Concentrate, remove the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, after concentration
To colistine sulfate concentrated solution 6.1 tons, adding 8.2 tons of defatted rice brans, stirring and evenly mixing also passes through pneumatic conveying drying, and final preparing contains
Amount is the colistine sulfate pre-mixing agent of 10%.
Embodiment 7
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after 60 tons of fermentation liquids of sulfur acid colistin are put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 6, after waiting pH stable, the fermentation of pH will be mixed up with dnockout pump
Liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 20000
Ultrafilter membrane carries out ultrafiltration, removes the impurity of macromole.Again the filtrate after ultrafiltration is carried out dense with the ultrafilter membrane of molecular cut off 800
Contracting, removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, obtains after concentration
Colistine sulfate concentrated solution 6.3 tons, adds 5 tons of zeolite powders, and stirring and evenly mixing also passes through pneumatic conveying drying, and the final content for preparing is
The colistine sulfate pre-mixing agent of 15%.
Comparative example 1
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, while stirring its pH value is adjusted to 12, with dnockout pump, the fermentation liquid mixing up pH is transported to after waiting pH stable
Ceramic membrane equipment filters, collects ceramic membrane filtrate.The ceramic membrane filtrate of collection is entered with the ultrafilter membrane of molecular cut off 10000
Row ultrafiltration, removes the impurity of macromole.Again the filtrate after ultrafiltration is concentrated with the ultrafilter membrane of molecular cut off 800, simultaneously
Remove the impurity of little molecule.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, obtains sulphuric acid and glue after concentration
Bacillin concentrated solution 60kg, adds 32 kg zeolite powders, and stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares colistine sulfate
Pre-mixing agent.After testing, the content of described colistine sulfate pre-mixing agent is almost 0, and well below intended 20%, its reason exists
In colistine sulfate extremely unstable under the strong alkali environment that pH is 12, cause decomposing in a large number.
Comparative example 2
Embodiment 2 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 1, after waiting pH stable, the fermentation of pH will be mixed up with dnockout pump
Liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 10000
Ultrafilter membrane carries out ultrafiltration, removes the impurity of macromole.Again the filtrate after ultrafiltration is carried out dense with the ultrafilter membrane of molecular cut off 800
Contracting, removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, obtains after concentration
Colistine sulfate concentrated solution 60kg, adds 32 kg precipitated calcium carbonates, and stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares sulfur
Acid colistin pre-mixing agent.After testing, the content of described colistine sulfate pre-mixing agent is 7%, and far below intended 20%, it is former
Because being that colistine sulfate is not sufficiently stable in the environment of pH is 1, there is decomposed.
Comparative example 3
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 5, after waiting pH stable, the fermentation of pH will be mixed up with dnockout pump
Liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 50000
Ultrafilter membrane carries out ultrafiltration, removes the impurity of macromole.Again the filtrate after ultrafiltration is carried out dense with the ultrafilter membrane of molecular cut off 800
Contracting, removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in single-pass evaporator, obtains after concentration
Colistine sulfate concentrated solution 69kg, adds 32 kg defatted rice brans, and stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares content
It it is the colistine sulfate pre-mixing agent of 20%.Although this comparative example has prepared the colistine sulfate premix that content is 20%
Agent, but in preparation process, the molecular weight retained due to ultrafiltration operation is excessive, causes macromole Impurity removal weak effect, institute
Stating in the second filtrate containing more macromole impurity, in operation is concentrated by ultrafiltration, blocking retains the ultrafilter membrane of small-molecular-weight and (sends out
Life blocks up film twice, the ultrafilter membrane that twice is changed molecular cut off 800), cause that efficiency is concentrated by ultrafiltration and cycles of concentration is low, also cause
The second follow-up enrichment process needs more energy consumption to concentrate；And, in described second enrichment process, have employed biography
The single-pass evaporator of system concentrates, and its energy consumption is relative to the plate-type evaporator of the present invention, Three-effect concentration device, MVR vaporizer more
Greatly.
Comparative example 4
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 4.5, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 10000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is entered with the ultrafilter membrane of molecular cut off 3000
Row concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in single-pass evaporator, after concentration
Obtaining colistine sulfate concentrated solution 56kg, add 32 kg defatted rice brans, stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares
Colistine sulfate pre-mixing agent.After testing, the content of described colistine sulfate pre-mixing agent is 6%, far below intended 20%, its
It is excessive that reason is to be concentrated by ultrafiltration molecular cut off in operation, causes a large amount of colistine sulfate to run off through ultrafilter membrane.
Comparative example 5
The prior art fermentation of employing company obtains colistine sulfate fermentation liquid, by the 600kg fermentation liquid of sulfur acid colistin
Squeeze into after putting tank in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.5, will mix up with dnockout pump after waiting pH stable
The fermentation liquid of pH is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate of collection with retaining molecule
The ultrafilter membrane of amount 10000 carries out ultrafiltration, removes the impurity of macromole.Again by the surpassing with molecular cut off 1000 of the filtrate after ultrafiltration
Filter membrane concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator,
Obtaining colistine sulfate concentrated solution 64kg after concentration, add 32 kg defatted rice brans, stirring and evenly mixing also passes through pneumatic conveying drying,
Prepare colistine sulfate pre-mixing agent eventually.After testing, the content of described colistine sulfate pre-mixing agent is 13%, less than intended
20%, its reason is that have employed the fermentation of non-invention method obtains colistine sulfate fermentation liquid, and in described fermentation liquid, sulphuric acid glues
Bacillin content is relatively low, and the impurity close with colistine sulfate molecular weight is more so that when step e takes more
Between.
Comparative example 6
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.5, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 10000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is entered with the ultrafilter membrane of molecular cut off 1000
Row concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, after concentration
Obtaining colistine sulfate concentrated solution 61kg, add 200 kg zeolite powders, stirring and evenly mixing also passes through pneumatic conveying drying, and final preparing contains
Amount is the colistine sulfate pre-mixing agent of 5%.Described content be 5% colistine sulfate pre-mixing agent add feedstuff as additive
Time, need the amount added relatively big, affect the appetite of domestic animal.
Comparative example 7
Embodiment 3 fermentation is used to obtain colistine sulfate fermentation liquid, after the 600kg fermentation liquid of sulfur acid colistin is put tank
Squeeze in storage tank, add concentrated sulphuric acid while stirring and its pH value is adjusted to 3.5, after waiting pH stable, sending out of pH will be mixed up with dnockout pump
Ferment liquid is transported in ceramic membrane equipment filter, and collects ceramic membrane filtrate.By the ceramic membrane filtrate collected with molecular cut off 10000
Ultrafilter membrane carry out ultrafiltration, remove the impurity of macromole.Again the filtrate after ultrafiltration is entered with the ultrafilter membrane of molecular cut off 1000
Row concentrates, and removes the impurity of little molecule simultaneously.Concentrated solution after finally being concentrated by ultrafilter membrane is squeezed in plate-type evaporator, after concentration
Obtaining colistine sulfate concentrated solution 61kg, add 4.5 kg defatted rice brans, stirring and evenly mixing also passes through pneumatic conveying drying, finally prepares
Content is the colistine sulfate pre-mixing agent of 40%.Described content is that the colistine sulfate pre-mixing agent of 40% is due to carrier defat rice
The proportion of bran is the least, causes pre-mixing agent quality unstable, the most not shelf-stable.
In sum, embodiment 1-embodiment 7 is successfully prepared colistine sulfate pre-mixing agent, and its preparation method is reasonable,
Solving the deficiencies in the prior art, yield is high, low cost, and whole technical process is all a physically separate process, does not use organic molten
Agent, is greatly decreased the generation of pollution, and achieves energy-saving and cost-reducing；And comparative example 1-comparative example 5 is due to preparation side
The problem that method exists, the colistine sulfate pre-mixing agent content even content that falls flat causing preparation is 0, or leads
The problems such as preparation process efficiency is low, energy consumption is big of cause；And the colistine sulfate pre-mixing agent of comparative example 6 preparation is due to content mistake
Low, when adding feedstuff as additive, need the amount added relatively big, affect the appetite of domestic animal, using effect is bad；And contrast reality
Although the colistine sulfate pre-mixing agent content executing example 7 preparation is the highest, but owing to carrier proportion is the least, causes pre-mixing agent
Quality is unstable, the most not shelf-stable.
Claims (10)
1. a preparation method for colistine sulfate pre-mixing agent, its feature comprises the following steps successively:
A. fermentation: by cultivating through one-level kind bottle after elder generation, two grades of kind bottles are cultivated, poly-viscosity bacillus culture fluid subcultivation after seed tank culture
To fermentation tank, carry out fermentation culture, obtain colistine sulfate fermentation liquid；
B. the pretreatment of fermentation liquid: colistine sulfate fermentation liquid sulphuric acid fermentation obtained adjusts pH to 2-6；
C. filter: the colistine sulfate fermentation liquid ceramic membrane filter of pH will be mixed up, and obtain the first filtrate；
D. ultrafiltration: described first filtrate is carried out ultrafiltration with the ultrafilter membrane retaining macromolecule, obtains the second filtrate；
E. first concentrate: described second filtrate is concentrated by ultrafiltration with the ultrafilter membrane retaining small-molecular-weight, obtains the first concentration
Liquid；
F. second concentrate: described first concentrated solution concentrator is concentrated, obtains the second concentrated solution；
G. it is dried: add carrier to the second concentrated solution and stir, and prepare colistine sulfate pre-mixing agent by pneumatic conveying drying.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step b
Colistine sulfate fermentation liquid with sulphuric acid adjust pH to 2.5-4.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step d
The ultrafilter membrane retaining macromolecule, its molecular cut off is 5000-20000 dalton.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step d
The ultrafilter membrane retaining macromolecule, its molecular cut off is 8000-15000 dalton.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step e
The ultrafilter membrane retaining small-molecular-weight, its molecular cut off is 500-1500 dalton.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step e
The ultrafilter membrane retaining small-molecular-weight, its molecular cut off is 500-1200 dalton.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step f
Concentrator be the one in plate-type evaporator, Three-effect concentration device, MVR vaporizer.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step g
Carrier be one or more in defatted rice bran, precipitated calcium carbonate, maize cob meal, wheat bran, zeolite powder.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that described in step a
One-level kind bottle cultivate the temperature with the cultivations of two grades of kind bottles be 27-31.5 DEG C, speed of agitator be 200-240rpm, incubation time be
20-28h, the temperature of described seed tank culture is 29.5-33.5 DEG C, speed of agitator is 70-90rpm, ventilation is 75-
85m3/ h, tank pressure are 0.02-0.03Mpa, pH value is 5.0-7.5, and cultivation cycle is 18-30h, the temperature of described fermentation culture
For 29.5-33.5 DEG C, speed of agitator be 60-100rpm, ventilation be 1:0.35-0.55, tank pressure be 0.02-0.03Mpa, pH value
For 5.8-6.0.
The preparation method of a kind of colistine sulfate pre-mixing agent the most according to claim 1, it is characterised in that step g system
Obtaining colistine sulfate pre-mixing agent content is 10%-20%.
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