CN106344520A - Preparation method of monensin premix - Google Patents
Preparation method of monensin premix Download PDFInfo
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- CN106344520A CN106344520A CN201610713598.8A CN201610713598A CN106344520A CN 106344520 A CN106344520 A CN 106344520A CN 201610713598 A CN201610713598 A CN 201610713598A CN 106344520 A CN106344520 A CN 106344520A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
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- Animal Behavior & Ethology (AREA)
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Abstract
The invention relates to a preparation method of a monensin premix. The method comprises the following steps: firstly, fermenting to obtain monensin fermentation liquor; heating up the fermentation liquor, and then concentrating to obtain monensin concentrate; then, adding a carrier into the concentrate, and evenly mixing to obtain mixed liquid of monensin and the carrier; finally, carrying out spraying granulation on the mixed liquid, drying and screening to obtain the monensin premix. The preparation method is green and environment-friendly, low in cost and high in efficiency.
Description
Technical field
The present invention relates to a kind of preparation method of monensin premix, belong to feed additive field.
Background technology
Monensin, also known as " Rumensin ", is a kind of material secreted by microorganism meat Cortex Cinnamomi ground streptomycete, its sodium salt
Polypide ionic equilibrium can be affected, cause polypide rupture dead, also there is volatile fatty acid ratio in control cud, reduce cud
The degraded of middle protein, reduces diet dry matter consumption, improves utilization of nutrients and improves the work such as animal energy utilization rate
With, extensively made an addition in the feedstuff of ruminant, be mainly used in preventing and treating chicken, lamb, calf, rabbit coccidiosis and promotion ruminate dynamic
Thing grows.
The existing production technology of monensin premix mainly has two kinds, and a kind of technology is solvent extraction method, and fermentation obtains
Monensin fermentation liquid, fermentation liquid is filtrated to get mycelium, and mycelium obtains sterling with solvent extraction again, then by sterling
It is mixed to get monensin premix with carrier.As patent cn103923099a discloses a kind of monensin crystal or its sodium salt
Preparation method, the method be by preprocessed for monensin fermentation liquid, decolouring separate out, organic solvent dissolving, crystallization and drip washing
Afterwards, convection drying obtain monensin crystal or plus alkali salt, be spray-dried obtain monensin sodium salt.The method needs to make
Use substantial amounts of organic solvent, and some nutrient substance in fermentation liquid are not used, finally produce a large amount of waste water and dregs, become
This height, pollution are big.Another kind of technology is filtration-comminution granulation, a kind of monensin premix as disclosed in patent cn102973516b
Agent preparation method, the method is that fermentation obtains monensin fermentation liquid, and fermentation liquid sodium hydroxide is adjusted and added Calcium Carbonate, plate after ph
Frame filters, and filter cake granulation machine sieves pelletize, dries and obtains monensin premix.The method adopts plate-and-frame filtration, granulation machine
Sieve pelletize, drying, whole process can not smoothness be carried out, cost of labor is big, and yield is restricted, create big simultaneously after filtering
The waste water containing nutrient substance for the amount, not only increases the processing cost of waste water, and also waste that a lot of microorganisms do not run out of can
Using material.
Content of the invention
It is an object of the invention to provide the preparation method of a kind of environmental protection, the monensin premix of stay in grade.
The above-mentioned technical purpose of the present invention has the technical scheme that
A kind of preparation method of monensin premix, its feature comprises the following steps successively:
A. ferment: carried out sending out successively after the postactivated Cortex Cinnamomi ground streptomyces species inoculation of the culture of kind of bottle, seed tank culture
Ferment is cultivated, and obtains monensin fermentation liquid；
B. concentrate: described monensin fermentation liquid is heated up, then fermentation liquid is placed in concentrator is concentrated, can not obtain
Rhzomorph concentrated solution；
C. mix: described monensin concentrated solution sodium hydroxide solution is adjusted ph and stirs, wait ph value stabilization
Add carrier while stirring afterwards, continue to stir, obtain the mixed liquor of monensin and carrier；
D. slurry-spraying pelletizing: the mixed liquor of described monensin and carrier is carried out slurry-spraying pelletizing and dry sieve gets monensin
Pre-mixing agent.
For solvent extraction method preparation monensin premix pollution big, not environmentally, the shortcoming of high cost and filtration-make
Grain method preparation monensin premix produce cannot serialization, the shortcomings of cost of labor is high, yield is limited, waste water is many, the present invention
A kind of preparation method of monensin premix is provided, the high fermentation liquid of Determination of Monensin in Zymotic Fluid is obtained by fermentation, by fermentation liquid
Concentrate and remove large quantity of moisture in fermentation liquid, then make monensin become monensin sodium salt with sodium hydroxide, then add carrier,
Form monensin premix mixed liquor, finally carry out slurry-spraying pelletizing, drying, obtain content and meet rule for 10%, 20%, 40% etc.
The monensin premix of lattice.The preparation method of the present invention does not need to use organic solvent, does not produce the waste water rich in Organic substance,
And there is continuous prodution.
Preferably, the cultivation temperature planting bottle culture described in step a is 31-33 DEG C, shaking speed turns for 240-260/
Point, incubation time is 18-20 h；The cultivation temperature of described seed tank culture is 31-33 DEG C, and ph value is 6.0-7.5, and tank pressure is
0.04mpa-0.06mpa, speed of agitator is 180-220 rev/min, and ventilation is 1:0.65-0.88, and incubation time is 20-26 h；
The cultivation temperature of described fermentation culture is 32-36 DEG C, and ph value is 6.0-7.5, and tank pressure is 0.03-0.06mpa, and speed of agitator is
115-145 rev/min, ventilation is 1:0.50-0.95, and incubation time is 350～430h.
Inventor finds, by the reasonable setting of step a and its technological parameter, can not in the monensin fermentation liquid obtaining
Rhzomorph content is high, does not produce the material of toxic and side effects in fermentation liquid.The fermentation liquid not having toxic and side effects material does not need increase to go
Except the operation of toxic and side effects material, it is that preparation method subsequent step of the present invention is carried out and prepares qualified monensin premix
The precondition of agent.
Preferably, described monensin fermentation liquid is warming up to 60-80 DEG C by step b.
First heat up and fermentation liquid is inactivated, allow the material degeneration such as protein in fermentation liquid, can precisely terminate to ferment.Inventor
Find, the end fermentation that do not heat up is it is impossible to control the metabolism of microorganism in the fermentation liquid into before concentrator；And be conducive to after heating up
Reduce the energy consumption of concentrator concentration process, shorten concentration time.
Preferably, concentrator described in step b be Three-effect concentration device, in plate-type evaporator, mvr vaporizer one
Kind.
Compared with traditional concentrator, described plate-type evaporator, Three-effect concentration device, mvr vaporizer concentration time are short, energy
Consumption is low.Inventor finds simultaneously, by described plate-type evaporator, Three-effect concentration device, mvr vaporizer control, to can not bacterium
The control of the concentrating degree of plain fermentation liquid is easier to grasp.
Preferably, dry biomass concentration is 20-45% in monensin concentrated solution described in step b.
Inventor finds, dry biomass concentration is the monensin concentrated solution of 20-45% advantageously in subsequent step
Carry out.
Preferably, monensin concentrated solution sodium hydroxide solution is adjusted ph value to 7.0-10.0 by step c.
By the addition of sodium hydroxide solution, monensin can be made to be converted into monensin sodium salt, inventor also finds,
When monensin concentrated solution sodium hydroxide solution adjusts ph value to 7.0-10.0, not only the changing effect of monensin sodium salt is
Good, and whole material is more uniform, the atomization during good fluidity of material, more conducively follow-up slurry-spraying pelletizing, is more favorable to
Improve the uniformity and the quality stability of monensin premix.
Preferably, carrier described in step c be precipitated calcium carbonate, in maize cob meal, defatted rice bran, 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
Pre-mixing agent stay in grade that carrier is mixed with described monensin concentrated solution and finally prepares, shelf-stable.
Preferably, the monensin described in step c is 25-50% with the dry biomass concentration of the mixed liquor of carrier.
Preferably, the monensin described in step c is 35-40% with the dry biomass concentration of the mixed liquor of carrier.
Inventor finds, has the monensin of reasonable dry biomass concentration and the mixed liquor of carrier advantageously in rear
The carrying out of continuous step；Inventor also finds, after the monensin concentrated solution described in step b adds carrier, dry biomass concentration
When improving 5-10 percentage point, the consumption of carrier is relatively reasonable.
Preferably, step a-d has the characteristics that continuous prodution.
Through inventor's design, step a-d has the characteristics that continuous prodution, to enter without by interrupting between step a-d
Pedestrian's work operates.
In sum, the method have the advantages that
1st, the preparation method of the present invention does not need, using a large amount of organic solvents, to produce large amount of organic waste water, and ferment
In liquid, Organic substance etc. is fully utilized, and does not produce waste residue, the preparation method green of the present invention, environmental protection, and it is useless to eliminate process
The cost of water waste residue, in fermentation liquid, whole monensin is all utilized.
2nd, each step of the preparation method of the present invention has the characteristics that continuous prodution, without interruption between each step, manually
Cost reduces, production efficiency is high, yield is high.
Brief description
Fig. 1 is the process chart of the present invention.
Specific embodiment
This specific embodiment is only explanation of the invention, and it is not limitation of the present invention, people in the art
Member can make to the present embodiment after reading this specification as needed does not have the modification of creative contribution, but as long as at this
All protected by Patent Law in the right of invention.
The preparation of fermentation liquid 1
Connect through the postactivated Cortex Cinnamomi ground streptomyces species of the culture of kind of bottle, seed tank culture successively by the preparation method of step a
Carry out fermentation culture after kind, obtain monensin fermentation liquid 1.The described cultivation temperature planting bottle culture is 32 DEG C, shaking speed
For 250 revs/min, incubation time is 19 h；The cultivation temperature of described seed tank culture is 32 DEG C, and ph value is 6.8, and tank pressure is
0.05mpa, speed of agitator is 200 revs/min, and ventilation is 1:0.75, and incubation time is 23 h；The culture temperature of described fermentation culture
Spend for 34 DEG C, ph value is 6.75, tank pressure is 0.045mpa, speed of agitator is 130 revs/min, ventilation is 1:0.7, incubation time
For 390h.
The preparation of fermentation liquid 2
Connect through the postactivated Cortex Cinnamomi ground streptomyces species of the culture of kind of bottle, seed tank culture successively by the preparation method of step a
Carry out fermentation culture after kind, obtain monensin fermentation liquid 2.The described cultivation temperature planting bottle culture is 31 DEG C, shaking speed
For 240 revs/min, incubation time is 20 h；The cultivation temperature of described seed tank culture is 31 DEG C, and ph value is 6.0, and tank pressure is
0.04mpa, speed of agitator is 180 revs/min, and ventilation is 1:0.65, and incubation time is 26h；The culture temperature of described fermentation culture
Spend for 32 DEG C, ph value is 6.0, tank pressure is 0.03mpa, speed of agitator is 115 revs/min, ventilation is 1:0.5, incubation time is
430h.
The preparation of fermentation liquid 3
Connect through the postactivated Cortex Cinnamomi ground streptomyces species of the culture of kind of bottle, seed tank culture successively by the preparation method of step a
Carry out fermentation culture after kind, obtain monensin fermentation liquid 3.The described cultivation temperature planting bottle culture is 33 DEG C, shaking speed
For 260 revs/min, incubation time is 18 h；The cultivation temperature of described seed tank culture is 33 DEG C, and ph value is 7.5, and tank pressure is
0.06mpa, speed of agitator is 220 revs/min, and ventilation is 1:0.88, and incubation time is 20h；The culture temperature of described fermentation culture
Spend for 36 DEG C, ph value is 7.5, tank pressure is 0.06mpa, speed of agitator is 145 revs/min, ventilation is 1:0.95, incubation time is
350h.
The preparation of fermentation liquid 4
Connect through the postactivated Cortex Cinnamomi ground streptomyces species of the culture of kind of bottle, seed tank culture successively by the preparation method of step a
Carry out fermentation culture after kind, obtain monensin fermentation liquid 4.The described cultivation temperature planting bottle culture is 35 DEG C, shaking speed
For 280 revs/min, incubation time is 22 h；The cultivation temperature of described seed tank culture is 35 DEG C, and ph value is 6.0, and tank pressure is
0.06mpa, speed of agitator is 240 revs/min, and ventilation is 1:1, and incubation time is 30h；The cultivation temperature of described fermentation culture is
36 DEG C, ph value is 7.5, and tank pressure is 0.08mpa, and speed of agitator is 160 revs/min, and ventilation is 1:1.2, and incubation time is 500h.
Embodiment 1
Preparation method is as follows:
A. ferment: using described monensin fermentation liquid 2.
B. concentrate: described monensin fermentation liquid 500kg is warming up to 60 DEG C, then fermentation liquid is placed in concentrator
Row concentrates, and obtains monensin concentrated solution；Described concentrator is Three-effect concentration device, dry in described monensin concentrated solution
Material mass concentration is 20%.
C. mix: described monensin concentrated solution sodium hydroxide solution regulation ph to 10.0 and is stirred,
Add carrier while stirring Deng after ph value stabilization, continue to stir, obtain the mixed liquor of monensin and carrier；Described load
Body is maize cob meal, and described monensin is 25% with the dry biomass concentration of the mixed liquor of carrier.
D. slurry-spraying pelletizing: the mixed liquor of described monensin and carrier is carried out slurry-spraying pelletizing, be dried after pelletize is good,
Screening, obtains monensin premix.
The technical parameter setting of embodiment 2-5 and comparative example's 1-5 preparation process and the difference such as following table institute of embodiment 1
Show:
Embodiment and comparative example's interpretation of result:
Embodiment 1-5 successfully prepares monensin premix up to specification, described monensin premix stay in grade,
Shelf-stable；Preparation process green, environmental protection, low cost, have continuous prodution feature, and cost of labor reduces, production efficiency is high, product
Amount is unrestricted.
Comparative example 1 does not first carry out hyperthermic treatment due to before not concentrating, and is simultaneously used traditional one way evaporation
Device, time-consuming, big energy-consuming to lead to concentration process.And, the monensin premix quality of final preparation is not sufficiently stable.
Comparative example 2 due to described in the monensin concentrated solution dry biomass concentration described in step b and step c not
Energy rhzomorph is excessive with the mixed liquor dry biomass concentration of carrier, leads to step d cannot be smoothed out, and then leads to not prepare
Obtain monensin premix up to specification.
Comparative example 3 is too small due to step b cycles of concentration, simultaneously the monensin concentrated solution dry described in step b
Mass concentration is too small with the mixed liquor dry biomass concentration of carrier with the monensin described in step c, and carrier addition
Very few, lead to step d to take long, and the monensin premix quality finally preparing be not sufficiently stable, not shelf-stable.
Although comparative example 4 has prepared monensin premix, through to monensin in preparation process
Fermentation liquid and the pre-mixing agent detection being obtained, find that in pre-mixing agent, Determination of Monensin in Zymotic Fluid is too low, the specification that the standard of not meeting specifies, and
And detect and find by-product containing toxic side effect, lead to this monensin premix cannot practical application.This is due to step a
Fermentation parameter setting is unreasonable, leads to Determination of Monensin in Zymotic Fluid in fermentation liquid low, creates poisonous pair simultaneously in sweat
The by-product of effect.
Although comparative example 5 has prepared monensin premix, through to monensin in preparation process
Fermentation liquid and the pre-mixing agent detection being obtained, find by-product containing toxic side effect, lead to this monensin premix actual
Application.This is because the fermentation liquid in market purchasing contains the by-product of toxic side effect.And due to sodium hydroxide use in step c
Amount is excessive, leads to the alkalescence of the monensin premix finally prepared not meet standard regulation.
In sum, the preparation method of the monensin premix of the present invention, needs to step a-d to carry out strict parameter
Control, could environmental protection, low cost, expeditiously prepare monensin premix up to specification.
Claims (10)
1. a kind of preparation method of monensin premix, its feature comprises the following steps successively:
A. ferment: carried out sending out successively after the postactivated Cortex Cinnamomi ground streptomyces species inoculation of the culture of kind of bottle, seed tank culture
Ferment is cultivated, and obtains monensin fermentation liquid；
B. concentrate: described monensin fermentation liquid is heated up, then fermentation liquid is placed in concentrator is concentrated, can not obtain
Rhzomorph concentrated solution；
C. mix: described monensin concentrated solution sodium hydroxide solution is adjusted ph and stirs, wait ph value stabilization
Add carrier while stirring afterwards, continue to stir, obtain the mixed liquor of monensin and carrier；
D. slurry-spraying pelletizing: the mixed liquor of described monensin and carrier is carried out slurry-spraying pelletizing and dry sieve gets monensin
Pre-mixing agent.
2. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that kind described in step a
The cultivation temperature of bottle culture is 31-33 DEG C, and shaking speed is 240-260 rev/min, and incubation time is 18-20 h；Described seed
The cultivation temperature of tank culture is 31-33 DEG C, and ph value is 6.0-7.5, and tank pressure is 0.04mpa-0.06mpa, and speed of agitator is 180-
220 revs/min, ventilation is 1:0.65-0.88, and incubation time is 20-26 h；The cultivation temperature of described fermentation culture is 32-36
DEG C, ph value is 6.0-7.5, and tank pressure is 0.03-0.06mpa, and speed of agitator is 115-145 rev/min, and ventilation is 1:0.50-
0.95, incubation time is 350～430h.
3. a kind of monensin premix according to claim 1 preparation method it is characterised in that step b by described not
60-80 DEG C can be warming up to for rhzomorph fermentation liquid.
4. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that dense described in step b
Contracting equipment is one of Three-effect concentration device, plate-type evaporator, mvr vaporizer.
5. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that described in step b not
In energy rhzomorph concentrated solution, dry biomass concentration is 20-45%.
6. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that step c will can not bacterium
Plain concentrated solution sodium hydroxide solution adjusts ph value to 7.0-10.0.
7. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that load described in step c
Body is one or more of precipitated calcium carbonate, maize cob meal, defatted rice bran, wheat bran, zeolite powder.
8. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that described in step c not
Can rhzomorph be 25-50% with the dry biomass concentration of the mixed liquor of carrier.
9. a kind of preparation method of monensin premix according to claim 8 is it is characterised in that described in step c not
Can rhzomorph be 35-40% with the dry biomass concentration of the mixed liquor of carrier.
10. a kind of preparation method of monensin premix according to claim 1 is it is characterised in that step a-d has
The feature of continuous prodution.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110592159A (en) * | 2019-09-23 | 2019-12-20 | 浙江拜克生物科技有限公司 | Preparation process and device of monensin premix |
| CN112680489A (en) * | 2021-01-15 | 2021-04-20 | 驻马店华中正大有限公司 | Method for improving monensin bioavailability |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0079707A1 (en) * | 1981-10-30 | 1983-05-25 | Eli Lilly And Company | Preparation of animal feed premixes |
| CN102973516A (en) * | 2012-12-05 | 2013-03-20 | 山东齐发药业有限公司 | Method for preparing monensin premix |
| CN103923099A (en) * | 2014-04-14 | 2014-07-16 | 宁夏泰瑞制药股份有限公司 | Preparation method of monensin crystal or sodium salt thereof |
| CN104313079A (en) * | 2014-11-03 | 2015-01-28 | 金河生物科技股份有限公司 | Preparation method of monensin premix |
-
2016
- 2016-08-24 CN CN201610713598.8A patent/CN106344520B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0079707A1 (en) * | 1981-10-30 | 1983-05-25 | Eli Lilly And Company | Preparation of animal feed premixes |
| CN102973516A (en) * | 2012-12-05 | 2013-03-20 | 山东齐发药业有限公司 | Method for preparing monensin premix |
| CN103923099A (en) * | 2014-04-14 | 2014-07-16 | 宁夏泰瑞制药股份有限公司 | Preparation method of monensin crystal or sodium salt thereof |
| CN104313079A (en) * | 2014-11-03 | 2015-01-28 | 金河生物科技股份有限公司 | Preparation method of monensin premix |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110592159A (en) * | 2019-09-23 | 2019-12-20 | 浙江拜克生物科技有限公司 | Preparation process and device of monensin premix |
| CN110592159B (en) * | 2019-09-23 | 2021-04-09 | 浙江拜克生物科技有限公司 | Preparation process and device of monensin premix |
| CN112680489A (en) * | 2021-01-15 | 2021-04-20 | 驻马店华中正大有限公司 | Method for improving monensin bioavailability |
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| Publication number | Publication date |
|---|---|
| CN106344520B (en) | 2019-03-12 |
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