CN108187027A - A kind of enramycin premix and preparation method thereof - Google Patents

A kind of enramycin premix and preparation method thereof Download PDF

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CN108187027A
CN108187027A CN201810278986.7A CN201810278986A CN108187027A CN 108187027 A CN108187027 A CN 108187027A CN 201810278986 A CN201810278986 A CN 201810278986A CN 108187027 A CN108187027 A CN 108187027A
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enramycin
mixed
powder
preparation
zymotic fluid
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CN108187027B (en
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杨林
钟迎东
周彦乐
叶朋
杨爱华
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INNER MONGOLIA BIOK BIOLOGY CO Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10Peptides having 12 to 20 amino acids
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1611Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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    • A61K9/1617Organic compounds, e.g. phospholipids, fats
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1617Organic compounds, e.g. phospholipids, fats
    • A61K9/1623Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
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    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
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    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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Abstract

The invention belongs to field of veterinary medicine preparation, are related to a kind of enramycin premix and preparation method thereof.Include the following steps:Enramycin zymotic fluid is pre-processed, and pretreated zymotic fluid is carried out ceramic filter, then using fluid bed, obtains enramycin dry product;It is input in airslide disintegrating mill by dry nitrogen after enramycin, diluent are ground, obtains mixed-powder I;It is sieved after corrigent is ground, with mixed-powder I ball milling mixings, obtains mixed-powder II;It is sieved after carrier is ground, with mixed-powder II ball milling mixings, obtains mixed-powder III;Mixed-powder III is put into granulator, mixing is to get enramycin premix after spraying into adhesive and wetting agent.This method is simple and feasible, easy to operate, at low cost, pollution is small, and pre-mixing agent curative effect stabilization, good drug efficacy, homogeneity height, the stability prepared are good.

Description

A kind of enramycin premix and preparation method thereof
Technical field
The invention belongs to field of veterinary medicine preparation, and in particular to a kind of enramycin premix and preparation method thereof.
Background technology
Enramycin, also known as enramycin, Enramycin, enramycin and enramycin etc., are obtained by actinomycete fermentation, It is the peptide antibiotics that unrighted acid is combined with ten several amino acid.Enramycin has gram-positive bacteria very strong work Property, it is particularly very strong to harmful clostridium restraint of enteral.It is not easy to develop immunity to drugs after long-time service, because it changes Become the bacterial flora in enteron aisle, so the utilizing status to nutritional ingredient in feed is good, due to only need to add micro grace draw it is mould Element can show excellent growth promotion and improve the effect of efficiency of feed utilization, and it has very high stability, low toxicity Property, low medicament residue, therefore recommended by many countries of the world as Animal feed-additive, be a kind of preferable feed addictive.
At present, the production technology of enramycin premix is mainly divided into two steps, and the first step is the system of enramycin product It is standby, enramycin zymotic fluid is directly filtered, it is dry either to the acidification of enramycin zymotic fluid, flocculation/organic solvent It slightly carries, macroreticular resin, which refines, etc. obtains enramycin;Second step is that enramycin product is mixed with pre-mixing agent with auxiliary material, by grace Mycin is drawn to be sieved respectively with auxiliary material to mix to get enramycin premix.For example, Chinese patent CN105104761A discloses one The method that kind prepares enramycin premix, the specific steps are:The enramycin zymotic fluid fermented is warming up to 70-75 DEG C, The composite antioxidant of the 0.5-1.0% of enramycin zymotic fluid quality is then added in, and adds in enramycin zymotic fluid quality The filter aid of 0-12% be stirred;Plate-frame filtering, expansion drying are carried out after fully stirring evenly, grace is made in addition auxiliary material dilution Draw mycin pre-mixing agent.Chinese patent CN102898509A discloses a kind of preparation method of enramycin crude product, by enramycin Zymotic fluid hydrochloric acid tune pH value obtains leachate with the isometric polar organic solvent of zymotic fluid adding in, leachate is consolidated Liquid isolates filtrate and filter residue, adds in pure water multipass poly (ether sulfone) film or polyetheramine film in filtrate, collects trapped fluid and drying. Chinese patent CN105535934A discloses a kind of enramycin premix and preparation method thereof, the pre-mixing agent by enramycin, The enramycin, organic acid, corrigent of recipe quantity are added in blending tank and mixed, added in by organic acid, corrigent, carrier composition Carrier needed for recipe quantity is mixed up to enramycin premix.
The preparation method of enramycin premix is had the following problems in the prior art, goes out tank to premix from zymotic fluid Agent finished product introduces soda acid or organic solvent in zymotic fluid, can cause the loss of enramycin, and product impurity to a certain extent It is more, quality is low;And direct filtration drying, quantities are big, filtering is incomplete, and loss of product is more;The type of additive, amount in auxiliary material Size not only affect the uniformity of pre-mixing agent, stability, also contribute to pre-mixing agent play in animal body effect length, Speed, and enramycin is had no targetedly directly to be simply mixed with auxiliary material, pre-mixing agent lack of homogeneity, stability can be caused It is low, effect is poor.
Invention content
The technical problems to be solved by the invention are in view of the foregoing drawbacks, to provide a kind of enramycin premix and its preparation Method.This method is simple and feasible, quality controllable, easy to operate, at low cost, pollution is small, and the pre-mixing agent curative effect prepared is stable, medicine It imitates, homogeneity is high, stability is good.
To achieve these goals, the present invention adopts the following technical scheme that:
A kind of preparation method of enramycin premix, includes the following steps:
(1) fermentation liquor pretreatment:Hydroxyethyl cellulose stirring is added in enramycin zymotic fluid, is added non-ionic poly- Acrylamide stirs, and adds filter aid later and is uniformly mixed the zymotic fluid pre-processed;
(2) it filters:Pretreated zymotic fluid is subjected to ceramic filter, then using fluidized bed drying, it is mould to obtain grace drawing Plain dry product;
(3) it mixes:It is input in airslide disintegrating mill, obtained mixed by dry nitrogen after enramycin, diluent are ground Close powder I;It is sieved after corrigent is ground, with mixed-powder I ball milling mixings, obtains mixed-powder II;It is sieved after carrier is ground, With mixed-powder II ball milling mixings, mixed-powder III is obtained;Mixed-powder III is put into granulator, sprays into adhesive and wetting Mixing is to get enramycin premix after agent.
There are its except a large amount of mycelium, strain metabolin, remaining culture medium and antibiotic major constituent in zymotic fluid His complex component, it is necessary to the modes such as be pre-processed, filtered and remove chaff interferent and obtain target product.It is pre-processed before filtering The first purpose is to change the physical property of zymotic fluid, in favor of filtering;Acid-base accommodation is not done in the present invention to zymotic fluid, directly with Hydroxyethyl cellulose and non-ionic polyacrylamide are as flocculant, and sodium bicarbonate is as filter aid;Hydroxyethyl cellulose was both Natural macromolecule flocculating agent can be used as, but also as the excipient of veterinary drug preparation, play the role of in the present invention it is flocculated, Just mix the uniformity for helping to improve follow-up pre-mixing agent early period with enramycin in technique;Non-ionic polyacrylamide causes Zymotic fluid further flocculates, and conducive to filtering, filter aid not only acts as the effect of aided filter herein, also functions to the work of excipient With.
The total mixed i.e. active ingredient and the mixed process of auxiliary material, one side Mixing Machine of pre-mixing agent play material mixing and make With, on the other hand due to being mixed between material particle there are relative density, granularity, the difference of surface characteristic, during exercise must Fixed also to generate automatic classification, automatic classification is destroyed the uniform state of material, therefore mixing of the application for material Further restriction has been done in mode and order by merging, largely improves the homogeneity, stability and safety of mixed material Property.
Further, in above-mentioned steps (1), hydroxyethyl cellulose addition be 1-3g/kg enramycin zymotic fluids, nonionic The addition of type polyacrylamide is 2-4g/kg enramycin zymotic fluids, and the addition of filter aid is 10-15g/kg enramycins Zymotic fluid, filter aid are sodium bicarbonate.
Further, hydroxyethyl cellulose stirring 10-20min is added in above-mentioned steps (1), in enramycin zymotic fluid, Non-ionic polyacrylamide stirring 30-50min is added, addition filter aid stirring 10-15min is uniformly mixed to obtain pre- later The zymotic fluid of processing.
Flocculant, which can assemble the suspended particulates in solution to be coupled, forms coarse cotton-shaped granule or agglomerate, for difference Zymotic fluid, the type of required flocculant, dosage, reaction time are also different, and flocculant additive amount is very few to be not achieved flocculation Effect excessively not only causes waste that can also cause with concentration increase and itself flocculates, reduced so as to cause flocculating effect.The present invention By the limitation in the type to flocculant and collocation and dosage and reaction time, optimal flocculating effect is realized, is improved Subsequent filter efficiency has saved the time, has reduced energy consumption.
Further, in above-mentioned steps (2), the vacuum degree of ceramic filter is -0.09~-0.08MPa, disc rotation speed 0.5- 1.0r/min;During fluidized bed drying, 40-50 DEG C of lathe bed temperature, drying time 30-40min.
In veterinary drug pre-mixing agent, the safety of drug and drug effect and homogeneity have a close relationship, pre-mixing agent product it is equal An important factor for one property is to ensure that product quality, and the selection of the homogeneity of product and auxiliary material and preparation process have close pass System, auxiliary material is the additives in addition to main ingredient in pharmaceutical preparation, in addition to inborn nature, serve as carrier, improve stability other than, also have increase The critical functions such as molten, hydrotropy, slow controlled release the effect of with improving drug, reduce adverse reaction and have very big relationship, and selection is suitable Auxiliary material is not only related to the homogeneity, mobility, stability of pre-mixing agent, is also relate to the safety of pre-mixing agent and the treatment of drug Effect.Inventor has obtained the technical solution of the application after the collocation of a large amount of different auxiliary materials and proportioning has been investigated.
Further, the dosage of enramycin is 8-12% in above-mentioned steps (3).
Adhesive is to make the tool of inviscid or sticky small material aggregation bonding into particle or compression forming sticking solid Body powder or thick liquid.Because the dissolubility of enramycin is poor, it is impossible to by water-soluble rear use, limit administering mode.This Application can both be mixed into feed and be administered by adding in adhesive and other auxiliary material enramycin premixes, can also be mixed into drink Water is administered.
Further, in above-mentioned steps (3), adhesive is sodium carboxymethylcellulose, hydroxypropyl cellulose and hypromellose It is one or more in element.
Further, in above-mentioned steps (3), by weight percentage, binder dosage 5-10%.
Corrigent means that, to improve or shield the pharmaceutic adjuvant of drug flavor in drug, enramycin has stink, this Shen Middle corrigent please be added in, on the one hand be improvement and shielding drug flavor, on the other hand be in certain journey using organic acid corrigent The dissolubility of enramycin can be increased on degree.
Further, in above-mentioned steps (3), corrigent is citric acid and sorbierite.
Further, in above-mentioned steps (3), by weight percentage, corrigent dosage is 2-7%, citric acid and sorb The weight ratio of alcohol is 2:1.
Diluent under normal circumstances, is for filling weight and volume, can also play the role of adhesive simultaneously;This Shen It please use specific diluent that can ensure that the mobility for premixing material is moderate, it is too smooth, it cannot be adsorbed onto on carrier, it is coarse Then cause to disperse uneven.
Further, in above-mentioned steps (3), diluent is microcrystalline cellulose.
Further, in above-mentioned steps (3), by weight percentage, diluent dosage is 10-20%.
Further, in above-mentioned steps (3), wetting agent is polysorbate80.
Further, in above-mentioned steps (3), by weight percentage, wetting agent dosage is 1-5%.
What carrier referred to receive and carry active constituent raises material, can play the role of dilution and improve mobility, So that active constituent is easier to be distributed in feed.
Further, in above-mentioned steps (3), carrier is corn flour, one or more in wheat bran, rice bran.
In pre-mixing agent production process, preparation process directly affects the homogeneity of product, does not require nothing more than accurate feed proportioning, must also Must ensure that active ingredient is uniform in pre-mixing agent by the gross must be distributed, equipment, material physical property, charge order, mixing in preparation process Time is all critically important factor.Inventor on the basis of many experiments have been carried out, has obtained the application according to working experience Technical solution.
Further, in step (3), 5-10min is ground after enramycin, diluent are mixed, is input to by dry nitrogen In airslide disintegrating mill, grain size D90≤30 μm mixed-powder I is obtained;60 mesh sieve is crossed after corrigent is ground 5-10min, with mixed powder Last I ball millings 10-15min mixing, obtains mixed-powder II;80 sieves are crossed after carrier is ground 5-10min, with mixed-powder II ball millings 15-25min mixings obtain mixed-powder III;80 sieves are crossed after adhesive grinding 5-10min, mixed-powder III is put into granulator In, mixing is to get enramycin premix after spraying into adhesive and wetting agent.
Further, in step (3), airslide disintegrating mill feed speed is 3.0-5.0kg/h, air pressure 2.5 × 105-4.5× 105Pa。
The present invention also provides a kind of enramycin premixes according to made from the above method.
Beneficial effects of the present invention:
(1) in preprocessing process, reaction condition is mild, belongs to physical reactions, and there is no chemical reaction, enramycin yields 100% can be kept, without any loss.
(2) filter aid and flocculant added in preprocessing process can be as the excipient of pre-mixing agent, and multi-purpose content is energy saving Subtract consumption.
(3) adhesive and organic acid are added in pre-mixing agent, increase the dissolubility of enramycin.
(4) it is reduced in pre-mixing agent preparation process using micronization technology, the grain size of enramycin, increases enramycin Dissolubility so that enramycin premix can both be mixed into feed administration, drinking water administration can also be mixed into.
(5) process for producing is simple and feasible, quality controllable, easy to operate, at low cost, pollution is small.
(6) pre-mixing agent curative effect stabilization, good drug efficacy, uniformity height, the stability prepared are good.
Specific embodiment
The present invention is further elaborated with reference to embodiments.These embodiments be only for illustrative purposes, And do not limit the scope of the invention and essence.Based on the embodiment of the present invention, those of ordinary skill in the art are not making wound All other embodiments obtained under the premise of the property made labour, belong to protection scope of the present invention.Tool is not specified in embodiment Body technique or condition person carry out according to conventional technique in the art or condition.
Enramycin zymotic fluid is provided by Inner Mongolia Biok Biology Co., Ltd., puts tank enramycin potency as 8970u/ mL;Non-ionic polyacrylamide is provided by Shijiazhuang Development Zone Desai Chemical Co., Ltd;Ceramic filter model BS30, It is provided by Bo Sheng Mechanology Inc..
Embodiment 1
Enramycin zymotic fluid 1000kg is taken to add in 2.5kg hydroxyethyl celluloses stirring 15min, add 3.0kg it is non-from Subtype polyacrylamide stirs 45min, adds sodium bicarbonate 15kg stirrings 10min later and is uniformly mixed the fermentation pre-processed Liquid;
Pretreated zymotic fluid is subjected to ceramic filter, then using the vacuum of fluidized bed drying, wherein ceramic filter It spends for -0.09MPa, disc rotation speed 0.8r/min;During fluidized bed drying, lathe bed temperature 50 C, drying time 35min; To enramycin dry product 87kg.
Embodiment 2
Enramycin zymotic fluid 1000kg is taken to add in 3kg hydroxyethyl celluloses stirring 20min, it is non-ionic to add 4kg Polyacrylamide stirs 50min, adds sodium bicarbonate 15kg stirrings 15min later and is uniformly mixed the zymotic fluid pre-processed;
Pretreated zymotic fluid is subjected to ceramic filter, then using fluidized bed drying, obtains enramycin dry product.
Influence of 1 device parameter of table to enramycin dry product yield
Embodiment 3
Enramycin zymotic fluid 1000kg is taken to add in 2kg hydroxyethyl celluloses stirring 15min, it is non-ionic to add 3kg Polyacrylamide stirs 40min, adds sodium bicarbonate 12kg stirrings 12min later and is uniformly mixed the zymotic fluid pre-processed;
Pretreated zymotic fluid is subjected to ceramic filter, then using fluidized bed drying, wherein, the vacuum of ceramic filter It spends for -0.09MPa, disc rotation speed 1.0r/min;During fluidized bed drying, lathe bed temperature 45 C, drying time 40min; To enramycin dry product 81kg.
Embodiment 4
Enramycin zymotic fluid 1000kg is taken to add in 1kg hydroxyethyl celluloses stirring 10min, it is non-ionic to add 2kg Polyacrylamide stirs 30min, adds sodium bicarbonate 10kg stirrings 10min later and is uniformly mixed the zymotic fluid pre-processed;
Pretreated zymotic fluid is subjected to ceramic filter, then using fluidized bed drying, wherein, the vacuum of ceramic filter It spends for -0.08MPa, disc rotation speed 0.5r/min;During fluidized bed drying, 40 DEG C of lathe bed temperature, drying time 30min; To enramycin dry product 78kg.
Embodiment 5
Preparation method:
The enramycin that Example 1 is prepared;10min is ground after enramycin 100g, diluent 200g are mixed, It is input in airslide disintegrating mill by dry nitrogen, obtains grain size D90≤30 μm mixed-powder I;After corrigent 50g is ground 10min 60 mesh sieve is crossed, is mixed with mixed-powder I ball millings 15min, obtains mixed-powder II;80 sieves are crossed after carrier 580g is ground 10min, with Mixed-powder II ball milling 25min mixings, obtain mixed-powder III;80 sieves are crossed after adhesive grinding 10min, mixed-powder III is thrown Enter in granulator, mixing is to get enramycin premix after spraying into adhesive 50g and wetting agent 20g.Wherein, airslide disintegrating mill Feed speed is 5.0kg/h, air pressure 4.5 × 105Pa。
In uniformity of dosage units, loss on drying, content of beary metal, arsenic salt content, water the detections such as dispersibility, stability according to 《Chinese veterinary pharmacopoeia》Described in method be measured.Wherein uniformity of dosage units should be not higher than 15, loss on drying≤10%, a huge sum of money Belong to content≤0.002%, arsenic salt content≤0.0002%, sedimentation volume ratio should be not less than 0.90;Pre-mixing agent specification is 4%, storage The condition of depositing is:Temperature (25 ± 2) DEG C, humidity (60 ± 5) %.
Influence of 2 different formulations of table for pre-mixing agent performance
Embodiment 6
Enramycin:100g is prepared in embodiment 1
Diluent:Microcrystalline cellulose 200g
Corrigent:Weight ratio is 2:1 citric acid and sorbierite 50g
Carrier:Corn flour 580g
Adhesive:Sodium carboxymethylcellulose 50g
Wetting agent:Polysorbate80 20g
Preparation method:
8min is ground after enramycin, diluent are mixed, is input in airslide disintegrating mill by dry nitrogen, obtains grain size D90≤30 μm mixed-powder I;60 mesh sieve is crossed after corrigent is ground 8min, mixes, must mix with mixed-powder I ball millings 10min Powder II;80 sieves are crossed after carrier is ground 8min, with mixed-powder II ball milling 20min mixings, obtain mixed-powder III;Adhesive 80 sieves are crossed after grinding 10min, mixed-powder III is put into granulator, mixing is drawn to get grace after spraying into adhesive and wetting agent Mycin pre-mixing agent.Wherein, airslide disintegrating mill feed speed is 4.0kg/h, air pressure 3.0 × 105Pa。
Contrast method 1:
After enramycin, diluent, corrigent, carrier, adhesive, wetting agent are crossed 80 mesh sieve respectively, it is uniformly mixed.
Contrast method 2:
1) enramycin crosses 80 mesh sieve;2) after diluent, corrigent, carrier, adhesive cross 80 mesh sieve respectively, equal increments It is uniformly mixed;3) it 1) will be uniformly mixed with 2) equal increments;4) mixing powder adds wetting agent to be uniformly mixed.
In uniformity of dosage units, loss on drying, content of beary metal, arsenic salt content, water the detections such as dispersibility, stability according to 《Chinese veterinary pharmacopoeia》Described in method be measured.Wherein uniformity of dosage units should be not higher than 15, loss on drying≤10%, a huge sum of money Belong to content≤0.002%, arsenic salt content≤0.0002%, sedimentation volume ratio should be not less than 0.90;Pre-mixing agent specification is 4%, storage The condition of depositing is:Temperature (25 ± 2) DEG C, humidity (60 ± 5) %.
Influence of the different preparation methods of table 3 for pre-mixing agent properties of product
Embodiment 7
Enramycin:80g is prepared in embodiment 1
Diluent:Microcrystalline cellulose 100g
Corrigent:Weight ratio is 2:1 citric acid and sorbierite 20g
Carrier:Wheat bran 740g corn flour, rice bran
Adhesive:Hydroxypropyl cellulose 50g sodium carboxymethylcelluloses and hydroxypropyl methylcellulose
Wetting agent:Polysorbate80 10g
Preparation method:
5min is ground after enramycin, diluent are mixed, is input in airslide disintegrating mill by dry nitrogen, obtains grain size D90≤30 μm mixed-powder I;60 mesh sieve is crossed after corrigent is ground 5min, mixes, must mix with mixed-powder I ball millings 15min Powder II;80 sieves are crossed after carrier is ground 5min, with mixed-powder II ball milling 15min mixings, obtain mixed-powder III;Adhesive 80 sieves are crossed after grinding 5min, mixed-powder III is put into granulator, mixing is drawn to get grace after spraying into adhesive and wetting agent Mycin pre-mixing agent.Wherein, airslide disintegrating mill feed speed is 3.0kg/h, air pressure 2.5 × 105Pa。
Embodiment 8
Enramycin:120g is prepared in embodiment 1
Diluent:Microcrystalline cellulose 200g
Corrigent:Weight ratio is 2:1 citric acid and sorbierite 70g
Carrier:Rice bran 460g
Adhesive:Hydroxypropyl methylcellulose 100g
Wetting agent:Polysorbate80 50g
Preparation method:
10min is ground after enramycin, diluent are mixed, is input in airslide disintegrating mill by dry nitrogen, obtains grain size D90≤30 μm mixed-powder I;60 mesh sieve is crossed after corrigent is ground 10min, mixes, obtains mixed with mixed-powder I ball millings 10min Close powder II;80 sieves are crossed after carrier is ground 10min, with mixed-powder II ball milling 25min mixings, obtain mixed-powder III;Bonding 80 sieves are crossed after agent grinding 10min, mixed-powder III are put into granulator, mixing is to get grace after spraying into adhesive and wetting agent Draw mycin pre-mixing agent.Wherein, airslide disintegrating mill feed speed is 5.0kg/h, air pressure 4.5 × 105Pa。
Embodiment 9
Influence of the feed containing enramycin to weaned piglets
(1) material
Experimental group 1:The enramycin premix that embodiment 5 is prepared;
Experimental group 2:The enramycin premix that embodiment 6 is prepared;
Control group:Commercially available 4% enramycin premix (buying in Jiangxi Hai Hui Dong Bao Science and Technology Ltd.s)
Blank group:Any medicament is not added.
(2) animal is chosen
The weanling pig 120 of 25 ± 2 ages in days is chosen, male and female is fifty-fifty to be tested, and is randomly divided into 4 groups, every group 30, respectively 2 nose heave multiple each repetitions 15.
(3) experimental design
Experimental group and control group feeding are added to the daily ration of pre-mixing agent by nutritional requirement;Blank group feeding does not add any medicine The daily ration of object.
Each group management measure always, respectively at formal test the 1st day, the 31st day early morning weighs, records each group piglet on an empty stomach Weight and health status.During experiment, piglet is allowed to be freely eaten daily, record the feed intake of each group;For every during experiment Group incidence is recorded, and do necessary timely processing.During experiment, fixed special messenger is responsible for and records, and keeps room Temperature is at 20-25 DEG C
Test index calculates:
Daily gain=(the last weight-experiment starting weight of experiment)/experiment number of days
Feed-weight ratio=total feed consumption amount/total augment weight
(4) experimental result
Experimental result is shown in Table 4
Influence of 4 enramycin premix of table to Production Performance of Weaning Pigs
Starting weight kg End weight kg Daily gain g Total feed consumption amount kg Feed-weight ratio
Experimental group 1 7.21±0.51 22.61±0.48 520 54 3.461538462
Experimental group 2 7.25±0.62 22.8±0.55 525 54 3.428571429
Control group 7.23±0.65 21.82±0.50 493 54 3.651115619
Blank group 7.24±0.74 20.57±0.69 451 54 3.99113082
Experimental group piglet daily gain is apparently higher than control group and blank group in the experiment periods of 30 days, and feed-weight ratio is less than control Group and blank group, piglet growth can be remarkably promoted by illustrating the enramycin premix of experimental group.
The foregoing is merely the preferred embodiment of the present invention, are not intended to limit the scope of the invention, every utilization The equivalent structure or equivalent flow shift that description of the invention is made directly or indirectly is used in other relevant technology necks Domain is included within the scope of the present invention.

Claims (10)

1. a kind of preparation method of enramycin premix, which is characterized in that include the following steps:
(1) fermentation liquor pretreatment:Hydroxyethyl cellulose stirring is added in enramycin zymotic fluid, adds non-ionic polypropylene Amide stirs, and adds filter aid later and is uniformly mixed the zymotic fluid pre-processed;
(2) it filters:Pretreated zymotic fluid is subjected to ceramic filter, then using fluid bed, obtains enramycin dry product;
(3) it mixes:It is input in airslide disintegrating mill by dry nitrogen after enramycin, diluent are ground, obtains mixed powder Last I;It is sieved after corrigent is ground, with mixed-powder I ball milling mixings, obtains mixed-powder II;It is sieved after carrier is ground, with mixing Powder II ball milling mixings are closed, obtain mixed-powder III;Mixed-powder III is put into granulator, after spraying into adhesive and wetting agent Mixing is to get enramycin premix.
2. preparation method according to claim 1, which is characterized in that in the step (1), hydroxyethyl cellulose addition For 1-3g/kg enramycin zymotic fluids, the addition of non-ionic polyacrylamide is 2-4g/kg enramycin zymotic fluids, is helped The addition of filtering agent is 10-15g/kg enramycin zymotic fluids, and filter aid is sodium bicarbonate.
3. preparation method according to claim 1, which is characterized in that in the step (1), add in enramycin zymotic fluid Enter hydroxyethyl cellulose stirring 10-20min, add non-ionic polyacrylamide stirring 30-50min, add drainage later Agent stirring 10-15min is uniformly mixed the zymotic fluid pre-processed.
4. preparation method according to claim 1, which is characterized in that in the step (2), the vacuum degree of ceramic filter For -0.09~-0.08MPa, disc rotation speed 0.5-1.0r/min;During fluidized bed drying, 40-50 DEG C of lathe bed temperature, when dry Between be 30-40min.
5. preparation method according to claim 1, which is characterized in that in the step (3), adhesive is carboxymethyl cellulose It is one or more in plain sodium, hydroxypropyl cellulose and hydroxypropyl methylcellulose.
6. preparation method according to claim 1, which is characterized in that in the step (3), corrigent is citric acid and mountain Pears alcohol.
7. preparation method according to claim 1, which is characterized in that in the step (3), diluent is microcrystalline cellulose Element.
8. preparation method according to claim 1, which is characterized in that in the step (3), wetting agent is polysorbate 80。
9. preparation method according to claim 1, which is characterized in that in the step (3), carrier for corn flour, wheat bran, It is one or more in rice bran.
10. a kind of enramycin premix according to made from any one of claim 1-9 preparation methods.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111903701A (en) * 2020-06-28 2020-11-10 武汉轻工大学 Fly-killing premix for animals and preparation method and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102949348A (en) * 2012-11-19 2013-03-06 清远容大生物工程有限公司 Enramycin dry suspension and preparation method thereof
CN104434777A (en) * 2014-12-29 2015-03-25 江西兴鼎科技有限公司 Method of improving stability of finished enramycin premixing agent
CN105104761A (en) * 2015-09-09 2015-12-02 石家庄高科动物保健品有限公司 Method for preparing enramycin premix

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102949348A (en) * 2012-11-19 2013-03-06 清远容大生物工程有限公司 Enramycin dry suspension and preparation method thereof
CN104434777A (en) * 2014-12-29 2015-03-25 江西兴鼎科技有限公司 Method of improving stability of finished enramycin premixing agent
CN105104761A (en) * 2015-09-09 2015-12-02 石家庄高科动物保健品有限公司 Method for preparing enramycin premix

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111903701A (en) * 2020-06-28 2020-11-10 武汉轻工大学 Fly-killing premix for animals and preparation method and application thereof

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