WO2016119491A1 - Procédé de préparation de prémélange à multiples antibiotiques - Google Patents

Procédé de préparation de prémélange à multiples antibiotiques Download PDF

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Publication number
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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WO
WIPO (PCT)
Prior art keywords
antibiotic
premix
preparation
antibiotics
acid
Prior art date
Application number
PCT/CN2015/092826
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English (en)
Chinese (zh)
Inventor
胡永红
曹翠翠
杨文革
杨洋
殷晶晶
Original Assignee
南京工业大学
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Application filed by 南京工业大学 filed Critical 南京工业大学
Publication of WO2016119491A1 publication Critical patent/WO2016119491A1/fr

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Classifications

    • 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%.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Toxicology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

La présente invention concerne un procédé de préparation de prémélange à multiples antibiotiques, comprenant les étapes suivantes : chauffer une liqueur de fermentation à multiples antibiotiques fermentés jusqu'à 60-70 °C, et maintenir pendant 5-10 minutes ; refroidir, ajuster le pH à 2,5-5,0 grâce à un acide, ajouter un agent stabilisant et un agent auxiliaire, bien mélanger, et effectuer une filtration à plateaux et cadres de la liqueur fermentée pour obtenir un gâteau de filtration humide à multiples antibiotiques ; puis effectuer une distillation éclair du gâteau de filtration et sécher, broyer, ajouter du matériau auxiliaire et diluer pour obtenir le prémélange à multiples antibiotiques. La présente invention est simple et facile à exploiter et de faible coût ; la stabilité du produit fini prémélange à multiples antibiotiques obtenu est visiblement améliorée pendant le processus de stockage, de façon que le prémélange à multiples antibiotiques soit plus pratique et plus stable pendant les processus de stockage, de transport et d'application.
PCT/CN2015/092826 2015-01-28 2015-10-26 Procédé de préparation de prémélange à multiples antibiotiques WO2016119491A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201510044283.4A CN104621156B (zh) 2015-01-28 2015-01-28 一种多抗霉素预混剂的制备方法
CN2015100442834 2015-01-28

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WO2016119491A1 true WO2016119491A1 (fr) 2016-08-04

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104621156B (zh) * 2015-01-28 2017-04-05 南京工业大学 一种多抗霉素预混剂的制备方法
CN110483617A (zh) * 2019-09-17 2019-11-22 陕西绿盾环境工程研究院有限公司 一种高含量多抗霉素原粉的制备方法
CN110592159B (zh) * 2019-09-23 2021-04-09 浙江拜克生物科技有限公司 一种莫能菌素预混剂的制备工艺及装置

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102424636A (zh) * 2011-09-27 2012-04-25 陕西绿盾生物制品有限责任公司 多抗霉素残渣生产有机肥的方法
CN102885056A (zh) * 2011-07-22 2013-01-23 湖北绿天地生物科技有限公司 一种纳他霉素制剂及其制备方法
CN103145489A (zh) * 2013-02-20 2013-06-12 游彩霞 一种多抗霉素可湿性粉剂及其制备方法
CN103230582A (zh) * 2013-04-17 2013-08-07 南京工业大学 一种持久霉素预混剂的制备方法
CN104621156A (zh) * 2015-01-28 2015-05-20 南京工业大学 一种多抗菌素预混剂的制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102885056A (zh) * 2011-07-22 2013-01-23 湖北绿天地生物科技有限公司 一种纳他霉素制剂及其制备方法
CN102424636A (zh) * 2011-09-27 2012-04-25 陕西绿盾生物制品有限责任公司 多抗霉素残渣生产有机肥的方法
CN103145489A (zh) * 2013-02-20 2013-06-12 游彩霞 一种多抗霉素可湿性粉剂及其制备方法
CN103230582A (zh) * 2013-04-17 2013-08-07 南京工业大学 一种持久霉素预混剂的制备方法
CN104621156A (zh) * 2015-01-28 2015-05-20 南京工业大学 一种多抗菌素预混剂的制备方法

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