WO2016119491A1 - Preparation method of multi-antibiotics premix - Google Patents
Preparation method of multi-antibiotics premix Download PDFInfo
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- WO2016119491A1 WO2016119491A1 PCT/CN2015/092826 CN2015092826W WO2016119491A1 WO 2016119491 A1 WO2016119491 A1 WO 2016119491A1 CN 2015092826 W CN2015092826 W CN 2015092826W WO 2016119491 A1 WO2016119491 A1 WO 2016119491A1
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- Prior art keywords
- antibiotic
- premix
- preparation
- antibiotics
- acid
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000003242 anti bacterial agent Substances 0.000 title abstract description 12
- 229940088710 antibiotic agent Drugs 0.000 title abstract description 12
- 238000000855 fermentation Methods 0.000 claims abstract description 44
- 230000004151 fermentation Effects 0.000 claims abstract description 44
- 238000001035 drying Methods 0.000 claims abstract description 14
- 239000003381 stabilizer Substances 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 5
- 239000000843 powder Substances 0.000 claims description 16
- 238000011085 pressure filtration Methods 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 12
- 238000005469 granulation Methods 0.000 claims description 10
- 230000003179 granulation Effects 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 8
- 238000007908 dry granulation Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 240000007594 Oryza sativa Species 0.000 claims description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 4
- 235000009566 rice Nutrition 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 3
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 claims description 3
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- SHFGJEQAOUMGJM-UHFFFAOYSA-N dialuminum dipotassium disodium dioxosilane iron(3+) oxocalcium oxomagnesium oxygen(2-) Chemical compound [O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[Na+].[Na+].[Al+3].[Al+3].[K+].[K+].[Fe+3].[Fe+3].O=[Mg].O=[Ca].O=[Si]=O SHFGJEQAOUMGJM-UHFFFAOYSA-N 0.000 claims description 3
- 239000010451 perlite Substances 0.000 claims description 3
- 235000019362 perlite Nutrition 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 229910021536 Zeolite Inorganic materials 0.000 claims description 2
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 2
- 229940113124 polysorbate 60 Drugs 0.000 claims description 2
- 239000010457 zeolite Substances 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims 1
- 239000010903 husk Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 abstract description 2
- 239000012065 filter cake Substances 0.000 abstract 2
- 238000001816 cooling Methods 0.000 abstract 1
- 238000007865 diluting Methods 0.000 abstract 1
- 238000007701 flash-distillation Methods 0.000 abstract 1
- 238000000227 grinding Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 208000031888 Mycoses Diseases 0.000 description 3
- 241000187747 Streptomyces Species 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229920002101 Chitin Polymers 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241001358680 Streptomyces aureochromogenes Species 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- 241000235349 Ascomycota Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229930191978 Gibberellin Natural products 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 206010027146 Melanoderma Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229930182764 Polyoxin Natural products 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000853 biopesticidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 210000003495 flagella Anatomy 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- IXORZMNAPKEEDV-UHFFFAOYSA-N gibberellic acid GA3 Natural products OC(=O)C1C2(C3)CC(=C)C3(O)CCC2C2(C=CC3O)C1C3(C)C(=O)O2 IXORZMNAPKEEDV-UHFFFAOYSA-N 0.000 description 1
- 239000003448 gibberellin Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004563 wettable powder Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/12—Powders or granules
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
- A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
- A01N47/12—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
Definitions
- the invention relates to a preparation method of a multi-antibiotic premix, in particular to a preparation method of a multi-antibiotic premix.
- Polyoxins also known as polyoxomycin, polyoxomycin, and plenum, are broad-spectrum agricultural antibiotics produced by modern bioengineering techniques. Multi-antibiotics have systemic and therapeutic effects and a high degree of target bioselectivity, which can specifically act on common fungal diseases of many crops. The most prominent antibiotics are the strong inhibitory effects on 25 fungal diseases such as flagellum, ascomycetes and semi-bacteria. Studies have shown that gibberellin has a total of 14 components from A to N. Since 1967, ubiquitin has been widely used as an agricultural fungicide for the treatment of rice sheath blight, tomato gray mold and pear black spot. Plant fungal diseases.
- Multi-antibiotics have a good inhibitory effect on the synthesis of chitin in fungal and insect cell walls.
- pluriticmycin has non-target biosafety to vertebrates and mammals.
- it also has a good inhibitory effect on the pathogenic cell Candida albicans causing mucosal and systemic infection.
- the multi-antibiotic has good adaptability and compatibility with nature, and it degrades quickly after application. It has no residue, no pollution, no cross-resistance and strong stability, and has become one of the first-line drugs for domestic bio-pesticide.
- the invention aims at the problem that the stability of the multi-antibiotic product is not strong, and provides a preparation method of the multi-antibiotic premix which is simple and easy, low in cost and obviously improved in stability of the obtained product.
- the technical scheme of the invention is: a preparation method of a multi-antibiotic premix, the specific steps of which are as follows:
- Pretreatment ferment the fermented multi-antibiotic fermentation liquid to 60-70 ° C for 5-10 min, cool, adjust the pH to 2.5-5.0 with acid, add stabilizer and auxiliary;
- step (1) the multi-antibiotic fermentation broth pretreated in step (1) is subjected to plate and frame press filtration to obtain a multi-antibiotic wet cake;
- step (3) flash drying pulverization: the wet cake obtained in step (2) is flash-dried, the inlet air temperature is controlled to 110-130 ° C, the outlet temperature is 60-70 ° C, the material temperature is 80-100 ° C, and after drying. Obtaining a multi-antibiotic mycelium dry product;
- premix According to the purity of the multi-antibiotic mycelium dry product and the content of the finished product, the powder carrier is added and uniformly mixed to obtain a powdery multi-antibiotic premix;
- Granulation The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation and sieved to obtain a granulated multi-antibiotic premix.
- the fermented titer of the fermented multi-antibiotic fermentation broth described in the step (1) is from 2000 to 2500 ⁇ g/mL.
- the medium and culture conditions for fermentation were disclosed in "A Streptomyces and Multi-antibiotic Metabolic Regulation Fermentation Process" (ZL201210056364.2) submitted by the research group.
- the fermentation broth of the fermentation broth was 2000-2500 ⁇ g/mL.
- the strain used in the fermentation is the self-screening Streptomyces aureochromogenes NJYHWG66382CGMCC No. 5756, which has been patented as ZL201210056364.2, and the invention title is "a Streptomyces and multi-antibiotic metabolism regulation process" invention patent
- the deposit was carried out in the middle of the general microbiology center of the China Microbial Culture Collection Management Committee. The deposit date was February 14, 2012. The patent was published on August 22, 2012, and the CGMCC No. 5756 strain was used. The species has been made public.
- the pressure of the plate frame press filtration described in the step (2) is 1.0 to 5.0 MPa, and the pressure filtration time is 1 to 2 hours.
- the multi-antibiotic wet cake described in the step (2) has a water content of 30 to 40%.
- the powder carrier in the step (4) is any one of rice hull powder, calcium carbonate, perlite and zeolite powder; the powder carrier has a particle size of 80 to 100 mesh; and the powder carrier is added in powder form.
- the multi-antibiotic premix has a mass of 55% to 81%.
- step (5) is subjected to dry granulation and passed through a sieve of 20 to 100 mesh.
- the invention pretreats the fermentation broth of the multi-antibiotic, thereby changing the quality of the multi-antibiotic premix product, so that the degradation degree of the multi-antibiotic is significantly reduced, and the stability of the multi-antibiotic premix product is greatly improved.
- the invention adopts the new process of preparing multi-antibiotic premix by plate frame filtration, flash drying, granulation, etc., the granulation rate and the yield of the multi-antibiotic premix are greatly improved, the cost is lowered, and the product is better. Adapt to market demand.
- the obtained multi-antibiotic premix has improved stability of titer, which makes it more convenient and stable in transportation, storage and application.
- the fermentation broth used is a fermentation broth obtained by fermentation of Streptomyces aureochromogenes NJYHWG66382CGMCC No. 5756. After the fermentation is completed, the stirring and temperature control are stopped, and the fermentation broth has a titer of 2000 to 2500 ⁇ g. /mL.
- the medium and culture conditions for the specific fermentation were carried out in accordance with "a Streptomyces and Multi-antibiotic Metabolic Regulation Fermentation Process" (ZL201210056364.2) submitted by the research group.
- Pretreatment Take 1000L fermentation broth of fermented multi-antibiotic fermentation liquid (fermentation titer is 2140 ⁇ g/mL) Heat to 60 ° C, maintain for 5 min, cool, adjust the pH to 2.5 with hydrochloric acid, add 1.5% copper sulfate as the stabilizer, and the fermentation liquid quality 0.2% Toween 80 as an auxiliary.
- step (2) Pressure filtration: the multi-antibiotic fermentation broth pretreated in step (1) is subjected to plate and frame pressure filtration, the pressure of the pressure filtration is controlled to 1.0 MPa, and the filtration time is 2 hours, and a multi-antibiotic wet cake having a water content of 30% is obtained. 174kg.
- Premix preparation 215.3 kg of rice hull powder was added to the dried product obtained in the step (3), and uniformly mixed to obtain 267.5 kg of a powdery multi-antibiotic premix having a multi-antibiotic content of 0.8%.
- Granulation The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through a 60-mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 60 mesh.
- the granulation rate and yield of the 0.8% multi-antibiotic premix prepared by the test were improved by about 15% and the stability was improved by about 9%.
- Pretreatment Take 1000L of fermented multi-antibiotic fermentation broth (fermentation titer of 2340 ⁇ g/mL) and heat to 65°C for 7min, cool, adjust the pH to 3.0 with phosphoric acid, and add 2.0% of the fermentation broth quality.
- Aluminum sulfate was used as a stabilizer, and the fermentation liquid quality was 0.25%, and the Span 60 was used as an auxiliary agent.
- step (1) the multi-antibiotic fermentation liquid pretreated in step (1) is subjected to plate and frame pressure filtration to control the pressure of the pressure filtration to be 2.0 MPa, and the filtration time is 1.5 hours to obtain a wet cake of water content of 34% more antibiotics. 156kg.
- Premix preparation 104 kg of calcium carbonate was added to the dried product obtained in the step (3), and the mixture was uniformly mixed to obtain 156 kg of a powdery multi-antibiotic premix having a mass content of 1.5%.
- Granulation The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through an 80-mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 80 mesh.
- the granulation rate and yield of the 1.5% multi-antibiotic premix prepared by the test are higher than those obtained by the conventional method. It is about 10% higher and the stability is increased by about 15%.
- Pretreatment Take 1000L of fermented multi-antibiotic fermentation broth (fermentation titer of 2250 ⁇ g/mL) and heat to 70°C for 10min, cool, adjust pH to 4.0 with citric acid, and add 3.0% of fermentation broth quality.
- Aluminum chloride was used as a stabilizer, and the fermentation liquid had a mass of 0.3% polysorbate 60 as an auxiliary.
- step (1) the multi-antibiotic fermentation liquid pretreated in step (1) is subjected to plate and frame pressure filtration to control the pressure of the pressure filtration to be 4.5 MPa, and the pressure filtration time is 2 hours, and the moisture content of the antibacterial wet cake of 40% is obtained. .
- Granulation The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through a 100 mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 100 mesh.
- the 2.0% multi-antibiotic premix prepared by the test has an increase in granulation rate and yield of about 20% and a stability improvement of about 10%.
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Agronomy & Crop Science (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Toxicology (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Disclosed in the present invention is a preparation method of multi-antibiotics premix, comprising steps of: heating fermented multi-antibiotics fermentation liquor up to 60-70 ˚C, and maintaining for 5-10 minutes; cooling, adjusting pH to 2.5-5.0 by acid, adding a stabilizing agent and an auxiliary agent, fully stirring, and carrying out plate-frame filtering on the fermented liquor to obtain a multi-antibiotics wet filter cake; then, carrying out flash distillation on the filter cake and drying, grinding, adding auxiliary material and diluting to obtain the multi-antibiotics premix. The present invention is simple and easy to operate and low in cost; the stability of the obtained multi-antibiotics premix finished product is obviously improved in the storage process, so that the multi-antibiotics premix is more convenient and stable in the processes of storage, transportation and application.
Description
本发明涉及一种多抗菌素预混剂的制备方法，尤其涉及一种多抗菌素预混剂的制备方法。The invention relates to a preparation method of a multi-antibiotic premix, in particular to a preparation method of a multi-antibiotic premix.
多抗菌素(Polyoxins)又名多抗霉素、多氧霉素、多效霉素，是一种用现代生物工程技术生产的肽嘧啶核苷类广谱农用抗生素。多抗菌素具有内吸性和治疗作用及高度的靶标生物选择性，其可专一地作用于多种作物的常见真菌性病害。多抗菌素最突出的是对鞭毛菌、子囊菌、半只菌等二十五种真菌性病害具有较强的抑制作用。研究表明，多效霉素共有A至N这14种成分组成，从1967年以来，多效霉素作为农用杀菌剂，广泛被用于治疗水稻纹枯病、番茄灰霉病和梨黑斑病等植物真菌病害。Polyoxins, also known as polyoxomycin, polyoxomycin, and plenum, are broad-spectrum agricultural antibiotics produced by modern bioengineering techniques. Multi-antibiotics have systemic and therapeutic effects and a high degree of target bioselectivity, which can specifically act on common fungal diseases of many crops. The most prominent antibiotics are the strong inhibitory effects on 25 fungal diseases such as flagellum, ascomycetes and semi-bacteria. Studies have shown that gibberellin has a total of 14 components from A to N. Since 1967, ubiquitin has been widely used as an agricultural fungicide for the treatment of rice sheath blight, tomato gray mold and pear black spot. Plant fungal diseases.
多抗菌素对于真菌和昆虫细胞壁几丁质的合成有很好的抑制作用，鉴于农作物和哺乳动物等体内不存在几丁质，所以多效霉素对脊椎动物和哺乳动物具有非靶标生物安全性，同时还对引起黏膜和全身性感染的病原细胞白色念珠菌有很好的抑制作用。多抗菌素与自然的适应性及相容性较好，施用后很快降解，无残留、无污染，不存在交叉耐药性及稳定性强等优点，已成为国内生物农药的一线药物之一。Multi-antibiotics have a good inhibitory effect on the synthesis of chitin in fungal and insect cell walls. In view of the absence of chitin in crops and mammals, pluriticmycin has non-target biosafety to vertebrates and mammals. At the same time, it also has a good inhibitory effect on the pathogenic cell Candida albicans causing mucosal and systemic infection. The multi-antibiotic has good adaptability and compatibility with nature, and it degrades quickly after application. It has no residue, no pollution, no cross-resistance and strong stability, and has become one of the first-line drugs for domestic bio-pesticide.
我国农药市场中多效霉素制剂剂型多种多样，其中有1.5％、2％、3％、10％的可湿性粉剂，1％、3％的水剂及32％的原药等，但此种剂型都存在储存过程中稳定性降低及运输不便等缺点。There are various dosage forms of pleomycin in the pesticide market in China, including 1.5%, 2%, 3%, 10% wettable powder, 1%, 3% aqueous solution and 32% original drug, etc. The dosage forms all have disadvantages such as reduced stability during storage and inconvenient transportation.
发明内容：Summary of the invention:
本发明针对多抗菌素成品稳定性不强的问题，提供了一种简单易行，成本低，所得产品稳定性明显提高的多抗菌素预混剂的制备方法。
The invention aims at the problem that the stability of the multi-antibiotic product is not strong, and provides a preparation method of the multi-antibiotic premix which is simple and easy, low in cost and obviously improved in stability of the obtained product.
本发明的技术方案为：一种多抗菌素预混剂的制备方法，其具体步骤如下：The technical scheme of the invention is: a preparation method of a multi-antibiotic premix, the specific steps of which are as follows:
(1)预处理：将发酵好的多抗菌素发酵液加热到60～70℃，维持5～10min，冷却，用酸调节pH至2.5～5.0，加入稳定剂和助剂；(1) Pretreatment: ferment the fermented multi-antibiotic fermentation liquid to 60-70 ° C for 5-10 min, cool, adjust the pH to 2.5-5.0 with acid, add stabilizer and auxiliary;
(2)压滤：将步骤(1)预处理后的多抗菌素发酵液进行板框压滤，得到多抗菌素湿滤饼；(2) Pressure filtration: the multi-antibiotic fermentation broth pretreated in step (1) is subjected to plate and frame press filtration to obtain a multi-antibiotic wet cake;
(3)闪蒸干燥粉碎：将步骤(2)得到的湿滤饼进行闪蒸干燥，控制进风温度为110～130℃，出风温度60～70℃，物料温度80～100℃，干燥后得到多抗菌素菌丝体干燥品；(3) flash drying pulverization: the wet cake obtained in step (2) is flash-dried, the inlet air temperature is controlled to 110-130 ° C, the outlet temperature is 60-70 ° C, the material temperature is 80-100 ° C, and after drying. Obtaining a multi-antibiotic mycelium dry product;
(4)预混剂制备：根据多抗菌素菌丝体干燥品纯度及成品要求含量，添加粉状载体，混合均匀，得到粉状多抗菌素预混剂；(4) Preparation of premix: According to the purity of the multi-antibiotic mycelium dry product and the content of the finished product, the powder carrier is added and uniformly mixed to obtain a powdery multi-antibiotic premix;
(5)造粒：将步骤(4)所得到的粉状多抗菌素预混剂进行干法制粒并过筛，得到颗粒状多抗菌素预混剂。(5) Granulation: The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation and sieved to obtain a granulated multi-antibiotic premix.
优选步骤(1)中所述的发酵好的多抗菌素发酵液的发酵效价为2000～2500μg/mL。发酵所用培养基及培养条件在本课题组提交的“一种链霉菌及多抗菌素代谢调控发酵工艺”(ZL201210056364.2)中进行了公开。具体方案为：酵母粉1.5～5.5g/L，玉米粉10～25g/L，黄豆饼粉15～30g/L，葡萄糖15～35g/L，氯化钠5～10g/L，碳酸钙10～15g/L，磷酸氢二钾2～4g/L，豆油5～15g/L，无机盐0.2～0.8g/L，pH值保持在6.0～7.2，控制罐压和温度，发酵进行55～65小时后，采用流加葡萄糖的方法进行补料分批发酵，使发酵过程中葡萄糖浓度保持在80～120g/L，发酵培养90～120h得发酵液，发酵液发酵效价为2000～2500μg/mL。发酵所用的菌种为自主筛选的金色产色链霉菌(Streptomyces aureochromogenes)NJYHWG66382CGMCC No.5756，已在专利号为ZL201210056364.2，发明名称为“一种链霉菌及多抗菌素代谢调控工艺”的发明专利中进行了保藏，保藏单位为中国微生物菌种保藏管理委员会普通微生物中心，保藏日期为2012年2月14日，该专利已于2012年8月22日进行了公开，所用的CGMCC No.5756菌种已经公开。Preferably, the fermented titer of the fermented multi-antibiotic fermentation broth described in the step (1) is from 2000 to 2500 μg/mL. The medium and culture conditions for fermentation were disclosed in "A Streptomyces and Multi-antibiotic Metabolic Regulation Fermentation Process" (ZL201210056364.2) submitted by the research group. The specific scheme is: yeast powder 1.5～5.5g/L, corn flour 10～25g/L, soybean cake powder 15～30g/L, glucose 15～35g/L, sodium chloride 5～10g/L, calcium carbonate 10～ 15g / L, dipotassium hydrogen phosphate 2 ~ 4g / L, soybean oil 5 ~ 15g / L, inorganic salt 0.2 ~ 0.8g / L, pH value maintained at 6.0 ~ 7.2, control tank pressure and temperature, fermentation for 55 ~ 65 hours After that, the fed-batch fermentation was carried out by adding glucose to maintain the glucose concentration in the fermentation process at 80-120 g/L, and the fermentation liquid was obtained by fermentation for 90-120 h. The fermentation broth of the fermentation broth was 2000-2500 μg/mL. The strain used in the fermentation is the self-screening Streptomyces aureochromogenes NJYHWG66382CGMCC No. 5756, which has been patented as ZL201210056364.2, and the invention title is "a Streptomyces and multi-antibiotic metabolism regulation process" invention patent The deposit was carried out in the middle of the general microbiology center of the China Microbial Culture Collection Management Committee. The deposit date was February 14, 2012. The patent was published on August 22, 2012, and the CGMCC No. 5756 strain was used. The species has been made public.
优选步骤(1)中调节pH值所用的酸为盐酸、硫酸、磷酸、柠檬酸、草酸
或甘氨酸；所述的稳定剂为硫酸铜、氯化铝、硫酸铝或氯化铁；稳定剂的加入量为发酵液质量1.5～2.5％；所述的助剂为Toween80、司盘60或聚山梨酯60；助剂的加入量为发酵液质量0.2～0.4％。Preferably, the acid used in the adjustment of the pH in the step (1) is hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, oxalic acid.
Or glycine; the stabilizer is copper sulfate, aluminum chloride, aluminum sulfate or ferric chloride; the stabilizer is added in an amount of 1.5 to 2.5% of the fermentation liquid; the auxiliary agent is Toween 80, Span 60 or poly The sorbate 60; the auxiliary agent is added in an amount of 0.2 to 0.4% by mass of the fermentation broth.
优选步骤(2)中所述的板框压滤的压力为1.0～5.0MPa，压滤时间为1～2h。优选步骤(2)中所述的多抗菌素湿滤饼的含水质量为30～40％。Preferably, the pressure of the plate frame press filtration described in the step (2) is 1.0 to 5.0 MPa, and the pressure filtration time is 1 to 2 hours. Preferably, the multi-antibiotic wet cake described in the step (2) has a water content of 30 to 40%.
优选步骤(4)中所述粉状载体为稻壳粉、碳酸钙、珍珠岩、沸石粉中的任一种；粉状载体的粒度为80～100目；粉状载体的加入量为粉状多抗菌素预混剂质量的55％～81％。优选步骤(5)干法制粒后过20～100目筛。Preferably, the powder carrier in the step (4) is any one of rice hull powder, calcium carbonate, perlite and zeolite powder; the powder carrier has a particle size of 80 to 100 mesh; and the powder carrier is added in powder form. The multi-antibiotic premix has a mass of 55% to 81%. Preferably, step (5) is subjected to dry granulation and passed through a sieve of 20 to 100 mesh.
1.本发明对多抗菌素的发酵液进行预处理，从而改变多抗菌素预混剂成品的品质使多抗菌素降解程度明显减少，使多抗菌素预混剂成品的稳定性大大提高。1. The invention pretreats the fermentation broth of the multi-antibiotic, thereby changing the quality of the multi-antibiotic premix product, so that the degradation degree of the multi-antibiotic is significantly reduced, and the stability of the multi-antibiotic premix product is greatly improved.
2.本发明采用板框过滤，闪蒸干燥，造粒等方法制备多抗菌素预混剂的新工艺，多抗菌素预混剂的成粒率和产量大大提高，成本降低，使该产品更好地适应市场需求。2. The invention adopts the new process of preparing multi-antibiotic premix by plate frame filtration, flash drying, granulation, etc., the granulation rate and the yield of the multi-antibiotic premix are greatly improved, the cost is lowered, and the product is better. Adapt to market demand.
3.所得多抗菌素预混剂效价稳定性提高，使其在在运输、存储及应用过程中更加方便、稳定。3. The obtained multi-antibiotic premix has improved stability of titer, which makes it more convenient and stable in transportation, storage and application.
下面结合实施例对本发明进行进一步的阐述，下述说明仅是为了解释本发明，并不对其内容进行限定。The invention is further illustrated by the following examples, which are merely illustrative of the invention and are not intended to limit the invention.
下述实施例中，所用发酵液以金色产色链霉菌(Streptomyces aureochromogenes)NJYHWG66382CGMCC No.5756发酵所得的发酵液为例，发酵完成后，停止搅拌和控温，发酵液发酵效价为2000～2500μg/mL。具体发酵所用培养基及培养条件按照本课题组提交的“一种链霉菌及多抗菌素代谢调控发酵工艺”(ZL201210056364.2)中进行。In the following examples, the fermentation broth used is a fermentation broth obtained by fermentation of Streptomyces aureochromogenes NJYHWG66382CGMCC No. 5756. After the fermentation is completed, the stirring and temperature control are stopped, and the fermentation broth has a titer of 2000 to 2500 μg. /mL. The medium and culture conditions for the specific fermentation were carried out in accordance with "a Streptomyces and Multi-antibiotic Metabolic Regulation Fermentation Process" (ZL201210056364.2) submitted by the research group.
实施例1：Example 1:
(1)预处理：取发酵好的多抗菌素发酵液1000L发酵液(发酵效价为2140μg/mL)
加热到60℃，维持5min，冷却，用盐酸调节pH至2.5，加入占发酵液质量1.5％的硫酸铜作为稳定剂、发酵液质量0.2％Toween80作为助剂。(1) Pretreatment: Take 1000L fermentation broth of fermented multi-antibiotic fermentation liquid (fermentation titer is 2140μg/mL)
Heat to 60 ° C, maintain for 5 min, cool, adjust the pH to 2.5 with hydrochloric acid, add 1.5% copper sulfate as the stabilizer, and the fermentation liquid quality 0.2% Toween 80 as an auxiliary.
(2)压滤：将步骤(1)预处理后的多抗菌素发酵液进行板框压滤，控制压滤压力为1.0MPa，压滤时间为2h，得到含水质量30％的多抗菌素湿滤饼174kg。(2) Pressure filtration: the multi-antibiotic fermentation broth pretreated in step (1) is subjected to plate and frame pressure filtration, the pressure of the pressure filtration is controlled to 1.0 MPa, and the filtration time is 2 hours, and a multi-antibiotic wet cake having a water content of 30% is obtained. 174kg.
(3)闪蒸干燥粉碎：将步骤(2)得到的湿滤饼进行闪蒸干燥，控制进风温度为110℃，出风温度65℃，物料温度85℃，干燥后得到多抗菌素菌丝体干燥品52.2kg。经检测得多抗菌素菌丝体干燥品中多抗菌素的重量百分含量为4.1％。(3) Flash drying pulverization: the wet cake obtained in the step (2) is subjected to flash drying, the inlet air temperature is controlled to 110 ° C, the outlet air temperature is 65 ° C, the material temperature is 85 ° C, and the multi-antibiotic mycelium is obtained after drying. Dry product 52.2kg. The multi-antibiotic content in the dried antibiotic mycelium dried product was found to be 4.1% by weight.
(4)预混剂制备：在步骤(3)中得到的干燥品中添加215.3kg的稻壳粉，混合均匀，得到267.5kg多抗菌素质量含量为0.8％的粉状多抗菌素预混剂。(4) Premix preparation: 215.3 kg of rice hull powder was added to the dried product obtained in the step (3), and uniformly mixed to obtain 267.5 kg of a powdery multi-antibiotic premix having a multi-antibiotic content of 0.8%.
(5)造粒：将步骤(4)所得到的粉状多抗菌素预混剂进行干法制粒，最后过60目筛，得到粒度为60目筛多抗菌素预混剂颗粒剂。(5) Granulation: The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through a 60-mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 60 mesh.
经检测所制得的0.8％多抗菌素预混剂比常规方法所制得的成粒率和产量提高约15％，稳定性提高约9％。The granulation rate and yield of the 0.8% multi-antibiotic premix prepared by the test were improved by about 15% and the stability was improved by about 9%.
实施例2：Example 2:
(1)预处理：取发酵好的多抗菌素发酵液1000L(发酵效价为2340μg/mL)温度加热到65℃，维持7min，冷却，用磷酸调节pH至3.0，加入占发酵液质量2.0％的硫酸铝作为稳定剂、发酵液质量0.25％司盘60作为助剂。(1) Pretreatment: Take 1000L of fermented multi-antibiotic fermentation broth (fermentation titer of 2340μg/mL) and heat to 65°C for 7min, cool, adjust the pH to 3.0 with phosphoric acid, and add 2.0% of the fermentation broth quality. Aluminum sulfate was used as a stabilizer, and the fermentation liquid quality was 0.25%, and the Span 60 was used as an auxiliary agent.
(2)压滤：将步骤(1)预处理后的多抗菌素发酵液进行板框压滤，控制压滤压力为2.0MPa，压滤时间为1.5h，得到含水质量34％多抗菌素湿滤饼156kg。(2) Pressure filtration: the multi-antibiotic fermentation liquid pretreated in step (1) is subjected to plate and frame pressure filtration to control the pressure of the pressure filtration to be 2.0 MPa, and the filtration time is 1.5 hours to obtain a wet cake of water content of 34% more antibiotics. 156kg.
(3)闪蒸干燥粉碎：将步骤(2)得到的湿滤饼进行闪蒸干燥，控制进风温度为120℃，出风温度70℃，物料温度95℃，干燥后得到多抗菌素菌丝体干燥品52kg。经检测得多抗菌素菌丝体干燥品中多抗菌素的重量百分含量为4.5％。(3) Flash drying pulverization: the wet cake obtained in the step (2) is flash-dried, the inlet air temperature is controlled to 120 ° C, the outlet air temperature is 70 ° C, the material temperature is 95 ° C, and the multi-antibiotic mycelium is obtained after drying. Dry product 52kg. The multi-antibiotic content in the dried antibiotic mycelium dried product was found to be 4.5% by weight.
(4)预混剂制备：在步骤(3)中得到的干燥品中添加104kg的碳酸钙，混合均匀，得到156kg多抗菌素质量含量为1.5％的粉状多抗菌素预混剂。(4) Premix preparation: 104 kg of calcium carbonate was added to the dried product obtained in the step (3), and the mixture was uniformly mixed to obtain 156 kg of a powdery multi-antibiotic premix having a mass content of 1.5%.
(5)造粒：将步骤(4)所得到的粉状多抗菌素预混剂进行干法制粒，最后过80目筛，得到粒度为80目筛多抗菌素预混剂颗粒剂。(5) Granulation: The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through an 80-mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 80 mesh.
经检测所制得的1.5％多抗菌素预混剂比常规方法所制得的成粒率和产量提
高约10％，稳定性提高约15％。The granulation rate and yield of the 1.5% multi-antibiotic premix prepared by the test are higher than those obtained by the conventional method.
It is about 10% higher and the stability is increased by about 15%.
实施例3：Example 3:
(1)预处理：取发酵好的多抗菌素发酵液1000L(发酵效价为2250μg/mL)温度加热到70℃，维持10min，冷却，用柠檬酸调节pH至4.0，加入发酵液质量3.0％的氯化铝作为稳定剂、发酵液质量0.3％聚山梨酯60作为助剂。(1) Pretreatment: Take 1000L of fermented multi-antibiotic fermentation broth (fermentation titer of 2250μg/mL) and heat to 70°C for 10min, cool, adjust pH to 4.0 with citric acid, and add 3.0% of fermentation broth quality. Aluminum chloride was used as a stabilizer, and the fermentation liquid had a mass of 0.3% polysorbate 60 as an auxiliary.
(2)压滤：将步骤(1)预处理后的多抗菌素发酵液进行板框压滤，控制压滤压力为4.5MPa，压滤时间为2h，得到含水质量40％多抗菌素湿滤饼125kg。(2) Pressure filtration: the multi-antibiotic fermentation liquid pretreated in step (1) is subjected to plate and frame pressure filtration to control the pressure of the pressure filtration to be 4.5 MPa, and the pressure filtration time is 2 hours, and the moisture content of the antibacterial wet cake of 40% is obtained. .
(3)闪蒸干燥粉碎：将步骤(2)得到的湿滤饼进行闪蒸干燥，控制进风温度为130℃，出风温度60℃，物料温度100℃，干燥后得到多抗菌素菌丝体干燥品50kg。经检测得多抗菌素菌丝体干燥品中多抗菌素的重量百分含量为4.5％。(3) Flash drying pulverization: the wet cake obtained in the step (2) is subjected to flash drying, the inlet air temperature is controlled to 130 ° C, the outlet air temperature is 60 ° C, the material temperature is 100 ° C, and the multi-antibiotic mycelium is obtained after drying. Dry product 50kg. The multi-antibiotic content in the dried antibiotic mycelium dried product was found to be 4.5% by weight.
(4)预混剂制备：在步骤(3)中得到的干燥品中添加62.5kg的珍珠岩，混合均匀，得到112.5kg多抗菌素质量含量为2.0％的粉状多抗菌素预混剂。(4) Preparation of premix: 62.5 kg of perlite was added to the dried product obtained in the step (3), and the mixture was uniformly mixed to obtain 112.5 kg of a powdery multi-antibiotic premix having a multi-antibiotic content of 2.0%.
(5)造粒：将步骤(4)所得到的粉状多抗菌素预混剂进行干法制粒，最后过100目筛，得到粒度为100目筛多抗菌素预混剂颗粒剂。(5) Granulation: The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation, and finally passed through a 100 mesh sieve to obtain a multi-antibiotic premix granule having a particle size of 100 mesh.
经检测所制得的2.0％多抗菌素预混剂比常规方法所制得的成粒率和产量提高约20％，稳定性提高约10％。
The 2.0% multi-antibiotic premix prepared by the test has an increase in granulation rate and yield of about 20% and a stability improvement of about 10%.
Claims (8)
- 一种多抗菌素预混剂的制备方法，其具体步骤如下：A method for preparing a multi-antibiotic premix, the specific steps of which are as follows:(1)预处理：将发酵好的多抗菌素发酵液加热到60～70℃，维持5～10min，冷却，用酸调节pH至2.5～5.0，加入稳定剂和助剂；(1) Pretreatment: ferment the fermented multi-antibiotic fermentation liquid to 60-70 ° C for 5-10 min, cool, adjust the pH to 2.5-5.0 with acid, add stabilizer and auxiliary;(2)压滤：将步骤(1)预处理后的多抗菌素发酵液进行板框压滤，得到多抗菌素湿滤饼；(2) Pressure filtration: the multi-antibiotic fermentation broth pretreated in step (1) is subjected to plate and frame press filtration to obtain a multi-antibiotic wet cake;(3)闪蒸干燥粉碎：将步骤(2)得到的湿滤饼进行闪蒸干燥，控制进风温度为110～130℃，出风温度60～70℃，物料温度80～100℃，干燥后得到多抗菌素菌丝体干燥品；(3) flash drying pulverization: the wet cake obtained in step (2) is flash-dried, the inlet air temperature is controlled to 110-130 ° C, the outlet temperature is 60-70 ° C, the material temperature is 80-100 ° C, and after drying. Obtaining a multi-antibiotic mycelium dry product;(4)预混剂制备：根据成品要求含量，添加粉状载体，混合均匀，得到粉状多抗菌素预混剂；(4) Preparation of premix: According to the content of the finished product, a powder carrier is added and uniformly mixed to obtain a powdery multi-antibiotic premix;(5)造粒：将步骤(4)所得到的粉状多抗菌素预混剂进行干法制粒并过筛，得到颗粒状多抗菌素预混剂。(5) Granulation: The powdery multi-antibiotic premix obtained in the step (4) is subjected to dry granulation and sieved to obtain a granulated multi-antibiotic premix.
- 根据权利要求1所述的制备方法，其特征在于步骤(1)中所述的发酵好的多抗菌素发酵液的发酵效价为2000～2500μg/mL。The preparation method according to claim 1, characterized in that the fermented titer of the fermented multi-antibiotic fermentation broth in the step (1) is from 2000 to 2500 μg/mL.
- 根据权利要求1所述的制备方法，其特征是：步骤(1)中调节pH值所用的酸为盐酸、硫酸、磷酸、柠檬酸、草酸或甘氨酸。The preparation method according to claim 1, wherein the acid used for adjusting the pH in the step (1) is hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, oxalic acid or glycine.
- 根据权利要求1所述的制备方法，其特征是：步骤(1)中所述的稳定剂为硫酸铜、氯化铝、硫酸铝或氯化铁；稳定剂的加入量为发酵液质量1.5～2.5％；所述的助剂为Toween80、司盘60或聚山梨酯60；助剂的加入量为发酵液质量0.2～0.4％。The preparation method according to claim 1, wherein the stabilizer in the step (1) is copper sulfate, aluminum chloride, aluminum sulfate or ferric chloride; the amount of the stabilizer added is 1.5 to the mass of the fermentation liquid. 2.5%; the auxiliary agent is Toween 80, Span 60 or Polysorbate 60; the auxiliary agent is added in an amount of 0.2 to 0.4% by mass of the fermentation liquid.
- 根据权利要求1所述的制备方法，其特征在于步骤(2)中所述的板框压滤的压力为1.0～5.0MPa，压滤时间为1～2h。The preparation method according to claim 1, characterized in that the pressure of the plate frame press filtration in the step (2) is 1.0 to 5.0 MPa, and the pressure filtration time is 1 to 2 hours.
- 根据权利要求1所述的制备方法，其特征是：步骤(2)中所述的多抗菌素湿滤饼的含水质量为30～40％。The preparation method according to claim 1, wherein the multi-antibiotic wet cake according to the step (2) has a water-containing mass of 30 to 40%.
- 根据权利要求1所述的制备方法，其特征是：步骤(4)中所述粉状载体为稻壳粉、碳酸钙、珍珠岩、沸石粉中的任一种；粉状载体的粒度为80～100目；粉状载体的加入量为粉状多抗菌素预混剂质量的55％～81％。The preparation method according to claim 1, wherein the powder carrier in the step (4) is any one of rice husk powder, calcium carbonate, perlite and zeolite powder; and the particle size of the powder carrier is 80. ~100 mesh; the powder carrier is added in an amount of 55% to 81% of the mass of the powdery multi-antibiotic premix.
- 根据权利要求1所述的制备方法，其特征在于步骤(5)干法制粒后过20～100目筛。 The preparation method according to claim 1, wherein the step (5) is subjected to dry granulation and passed through a sieve of 20 to 100 mesh.
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| CN102885056A (en) * | 2011-07-22 | 2013-01-23 | 湖北绿天地生物科技有限公司 | Natamycin preparation and preparation method thereof |
| CN103145489A (en) * | 2013-02-20 | 2013-06-12 | 游彩霞 | Wettable polyoxin powder and its preparation method |
| CN103230582A (en) * | 2013-04-17 | 2013-08-07 | 南京工业大学 | Enramycin premix preparation method |
| CN104621156A (en) * | 2015-01-28 | 2015-05-20 | 南京工业大学 | Preparation method of multi-antibiotics premix |
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| CN102424636A (en) * | 2011-09-27 | 2012-04-25 | 陕西绿盾生物制品有限责任公司 | Method for producing organic fertilizer by polyoxin residue |
| CN103145489A (en) * | 2013-02-20 | 2013-06-12 | 游彩霞 | Wettable polyoxin powder and its preparation method |
| CN103230582A (en) * | 2013-04-17 | 2013-08-07 | 南京工业大学 | Enramycin premix preparation method |
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