SK6642000A3 - Method for isolating salinomycin from fermentation broth - Google Patents

Method for isolating salinomycin from fermentation broth Download PDF

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SK6642000A3
SK6642000A3 SK6642000A SK6642000A SK6642000A3 SK 6642000 A3 SK6642000 A3 SK 6642000A3 SK 6642000 A SK6642000 A SK 6642000A SK 6642000 A SK6642000 A SK 6642000A SK 6642000 A3 SK6642000 A3 SK 6642000A3
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salinomycin
fermented soil
biomass
fermented
soil
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SK6642000A
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Slovak (sk)
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SK283167B6 (en
Inventor
Maria Jakubcova
Dusan Lucina
Milos Bosansky
Gabriela Borosova
Pavol Ivanic
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Biotika As
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Priority to SK664-2000A priority Critical patent/SK283167B6/en
Priority to CZ20023429A priority patent/CZ20023429A3/en
Priority to AU2001255144A priority patent/AU2001255144A1/en
Priority to PCT/SK2001/000015 priority patent/WO2001083801A2/en
Priority to DE10196144T priority patent/DE10196144T1/en
Priority to SI200120024A priority patent/SI21043A/en
Priority to BR0110589-2A priority patent/BR0110589A/en
Priority to CA002407708A priority patent/CA2407708A1/en
Publication of SK6642000A3 publication Critical patent/SK6642000A3/en
Publication of SK283167B6 publication Critical patent/SK283167B6/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/181Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Processing Of Solid Wastes (AREA)
  • Soil Conditioners And Soil-Stabilizing Materials (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed is a method for isolation of salinomycin, wherein the granulated product is obtained. The isolation consists in that the fermented soil of salinomycin is modified into the acid area of pH. To the modified fermented soil the inert filtration agent is added, preferably diatomaceous earth, zeolites, woody powder, respectively their mixture, in the amount of 5 to 20 % per volume of fermented soil. The biomass is separated by filtration and goes through the granulation into the fluid stove, the obtained product is ground and sifted.

Description

Vynález sa týka spôsobu izolácie salinomycínu z vyfermentovanej pôdy.The invention relates to a process for the isolation of salinomycin from fermented soil.

Doterajší stav technikyBACKGROUND OF THE INVENTION

Salinomycín feed gráde sa pripravuje rozprašovacím sušením vyfermentovaných pôd spolu s protispekacím činidlom a plnidlom alebo sa izoluje do čistej formy po oddelení biomasy extrakciou, zakoncentrovaním a čistením rekryštalizáciou surového produktu. Izolácia do čistej formy je náročná na výrobné náklady a strojnotechnologické vybavenie prevádzky (US pat. spis 4,212,942, US pat. spis. 4,137,247).Salinomycin feed batch is prepared by spray-drying the fermented soils together with an anti-caking agent and a filler or isolated to a pure form after separation of the biomass by extraction, concentration and purification by recrystallization of the crude product. Insulation to pure mold is demanding on manufacturing costs and plant engineering equipment (US Pat. No. 4,212,942, US Pat. No. 4,137,247).

Pre použitie salinomycínu ako veterinárne liečivo alebo aj ako stimulátor rastu nie je potrebné pripraviť čistú formu. Po vyfermentovaní a úprave je možné priamo vysušiť pôdu spolu s pŕotispekacími látkami, pričom sa pred sušením môže zahustiť na odparke (US pat. spis 4,395,491).It is not necessary to prepare a pure form for the use of salinomycin as a veterinary drug or as a growth promoter. After fermentation and treatment, the soil can be directly dried together with antiseptics, and can be concentrated on a evaporator prior to drying (U.S. Pat. No. 4,395,491).

Vyfermentovaná pôda salinomycínu obsahuje množstvo balastných látok, ktoré robia problémy po vysušení na rozprašovacej sušiarni. Pevné látky sa zhlukujú, tvoria hrudy, ktoré sa už ďalej nedajú spracovať. Hlavnou príčinou tvorby aglomerátov je obsah tukov. Tuky obsiahnuté v pevných látkach sa prejavujú hlavne pri spracovaní pri vysokých teplotách, vlhkosti a pri mechanickom namáhaní. Produkt z rozprašovacej sušiarne je veľmi prašný a je potrebné ho granulovať (US pat. spis 5,529,911). Granuláciu je možné robiť priamo v kombinovanej rozprašovacej sušiarni s fluidným lôžkom, alebo ako ďalší izolačný krok suchou alebo mokrou cestou.The fermented soil of salinomycin contains a number of ballast substances which cause problems after drying in a spray drier. Solids aggregate, forming lumps that can no longer be processed. The main cause of agglomerate formation is the fat content. The fats contained in solids are particularly evident when processed at high temperatures, humidity and mechanical stress. The spray dryer product is very dusty and needs to be granulated (U.S. Pat. No. 5,529,911). The granulation can be carried out directly in a combined fluidized bed spray drier or as a further isolation step by dry or wet process.

Zistilo sa, že pevná látka vo forme granúl sa dá izolovať zo salinomycínovej vyfermentovanej pôdy bez toho, aby došlo k zhlukovaniu.It has been found that a granular solid can be isolated from salinomycin fermented soil without agglomeration.

Podstata vynálezuSUMMARY OF THE INVENTION

Uvedené nevýhody odstraňuje postup izolácie salinomycínu z fermentačnej pôdy podľa vynálezu, ktorého podstata spočíva v tom, že vyfermentovaná pôda salinomycínu sa upraví do kyslej oblasti pH na hodnotu 4 až 5. K upravenej vyfermentovanej pôde sa pridá inertný filtračný prostriedok, s výhodou kremelina, zeolity, drevitá múčka, respektíve ich zmes, v množstve 5 až 20 % na hmotnosť vyfermentovanej pôdy.The above-mentioned disadvantages are eliminated by the process of isolating salinomycin from the fermentation broth according to the invention, which consists in adjusting the fermented broth of salinomycin to an acidic pH range of 4 to 5. An inert filtering agent, preferably diatomaceous earth, zeolites, is added to the treated fermented broth. wood flour or mixture thereof in an amount of 5 to 20% by weight of the fermented soil.

Biomasa sa oddelí filtráciou a postupuje cez granuláciu do fluidnej sušiarne, získaný produkt sa melie a situje.The biomass is collected by filtration and passed through granulation to a fluid bed drier, the product obtained is ground and sieved.

Uvedený postup zabezpečuje produkt, u ktorého nedochádza ku zhlukovaniu častíc. Výhodou je, že účinná látka sa nachádza v kyslej oblasti hodnôt pH v bunkách biomasy a tak je možné odseparovaný filtrát, získaný týmto postupom, vypúšťať na aeróbne spracovanie na biologickú čističku odpadných vôd. Ďalšou výhodou je, že získaná biomasa má vyššiu sušinu ako vyfermentovaná pôda a na jej vysušenie je tak potrebná nižšia spotreba energie ako na celú vyfermentovanú pôdu.This process provides a product that does not agglomerate. The advantage is that the active substance is in the acidic pH range of the biomass cells and thus the separated filtrate obtained by this process can be discharged for aerobic treatment to a biological waste water treatment plant. A further advantage is that the biomass obtained has a higher dry matter content than fermented soil and thus requires less energy to dry than the entire fermented soil.

Príklady vykonania vynálezuDETAILED DESCRIPTION OF THE INVENTION

Príklad 1Example 1

Fermentačná pôda získaná fermentáciou Streptomyces albus mala po 128 hod. kultivácie pH 6,1 a obsah salinomycínu 18,4 g/kg. 527 kg vyfermentovanej pôdy bolo upravené prídavkom 10%-nej HC1 na hodnotu pH 4,0. K upravenej vyfermentovanej pôde sa pridala drevitá múčka v množstve 8 % na hmotnosť vyfermentovanej pôdy. Filtráciou na rotačnom vákuovom filtri nabalenom drevitou múčkou sa získalo 119,7 kg biomasy a 460,7 kg filtrátu s obsahom salinomycínu pod 0,01%, ktorý po neutralizácii pokračoval na aeróbne čistenie odpadných vôd. Odseparovaná biomasa postupovala cez granulátor do fluidnej sušiarne, kde sa sušením získalo 74,2 kg produktu s obsahom 12,3 % salinomycínu.The fermentation broth obtained by fermentation of Streptomyces albus had after 128 hours. cultivation pH 6.1 and salinomycin content 18.4 g / kg. 527 kg of fermented soil was adjusted to pH 4.0 by addition of 10% HCl. Wood flour was added to the treated fermented soil in an amount of 8% by weight of the fermented soil. Filtration on a rotary vacuum filter packed with wood flour yielded 119.7 kg of biomass and 460.7 kg of a filtrate with salinomycin content below 0.01%, which after neutralization continued for aerobic wastewater treatment. The separated biomass was passed through a granulator to a fluid-bed dryer, where 74.2 kg of product containing 12.3% salinomycin were dried.

Príklad 2Example 2

Fermentačná pôda získaná fermentáciou Streptomyces albus ' mala po 120 hod. kultivácie pH 6,0 a obsah salinomycínu 22,6 g/kg. 589 kg vyfermentovanej pôdy bolo upravené prídavkom 10%-nej HC1 na hodnotu pH 5,0. K upravenej vyfermentovanej pôde sa pridal zeolit a kremelina v množstve 15 % na hmotnosť vyfermentovanej pôdy. Filtráciou na rotačnom vákuovom filtri nabalenom kremelinou sa získalo 184,7 kg biomasy a 495,6 kg fíltrátu s obsahom salinomycínu pod 0,02%, ktorý bol likvidovaný ako v príklade 1. Odseparovaná biomasa postupovala cez granulátor do fluidnej sušiarne, kde sa sušením získalo 106,5 kg produktu s obsahom 12,1 % salinomycínu.The fermentation broth obtained by fermentation of Streptomyces albus' had after 120 hours. cultivation pH 6.0 and salinomycin content 22.6 g / kg. 589 kg of fermented soil was adjusted to pH 5.0 by addition of 10% HCl. Zeolite and diatomaceous earth were added to the treated fermented soil in an amount of 15% by weight of the fermented soil. Filtration on a rotary vacuum filter packed with diatomaceous earth yielded 184.7 kg of biomass and 495.6 kg of the filtrate with salinomycin content below 0.02%, which was discarded as in Example 1. The separated biomass was passed through a granulator to a fluidized bed dryer where drying was obtained 106.5 kg of product containing 12.1% salinomycin.

Príklad 3Example 3

Fermentačná pôda získaná fermentádou Streptomyces albus ‘ , mala po 124 hod. kultivácie pH 6,2 a obsah salinomycínu 17,1 g/kg. Prídavkom roztoku NaOH bola upravená hodnota pH na 7 až 8. Takto upravená vyfermentovaná pôda sa vyhriala na teplotu 60°C a po ochladení sa pH upravilo zriedenou kyselinou chlorovodíkovou, tak ako v príklade 1. K 524 kg upravenej vyfermentovanej pôdy sa pridal zeolit v množstve 20% na hmotnosť vyfermentovanej pôdy. Filtráciou na rotačnom vákuovom filtri nabalenom kremelinou sa získalo 184,7 kg biomasy a 495,6 kg fíltrátu s obsahom salinomycínu pod 0,001 %. Likvidácia fíltrátu ako v príklade 1. Odseparovaná biomasa postupovala cez granulátor do fluidnej sušiarne, kde sa sušením získalo 80,7 kg produktu s obsahom 10,9 % salinomycínu.The fermentation broth obtained by Streptomyces albus ferment fermentation was after 124 hours. cultivation pH 6.2 and salinomycin content 17.1 g / kg. The pH was adjusted to 7-8 by the addition of NaOH solution. The fermented soil thus treated was heated to 60 ° C and after cooling the pH was adjusted with dilute hydrochloric acid as in Example 1. Zeolite was added to 524 kg of treated fermented soil. 20% by weight of fermented soil. Filtration on a rotary vacuum filter packed with diatomaceous earth yielded 184.7 kg of biomass and 495.6 kg of the filtrate with salinomycin content below 0.001%. Disposal of the filtrate as in Example 1. The separated biomass was passed through a granulator to a fluid-bed dryer where 80.7 kg of product containing 10.9% salinomycin were dried.

Príklad č.4Example 4

Fermentačná pôda získaná fermentádou Streptomyces albus mala po 120 hod. kultiváde pH 6,3 a obsah salinomycínu 15,5 g/kg. 566,6 kg vyfermentovanej pôdy bolo upravené prídavkom 10% HC1 na hodnotu pH 4,7. K upravenej vyfermentovanej pôde sa pridala kremelina v množstve 5 % na hmotnosť vyfermentovanej pôdy. Filtrádou na rotačnom vákuovom filtri nabalenom kremelinou sa získalo 100,7 kg biomasy. 500,6 kg fíltrátu s nízkym obsahom salinomydnu, ktorý po neutralizácii pokračoval na aeróbne čistenie odpadných vôd. Odseparovaná biomasa postupovala cez granulátor do fluidnej sušiarne, kde sa sušením získalo 68,4 kg suchého produktu. Obsah salinomycínu v produkte je 12,8 %.The fermentation broth obtained by Streptomyces albus fermentation was after 120 hours. cultivation pH 6.3 and salinomycin content 15.5 g / kg. 566.6 kg of fermented soil was adjusted to pH 4.7 by the addition of 10% HCl. Kieselguhr was added to the treated fermented soil in an amount of 5% by weight of the fermented soil. A filter on a rotary vacuum filter packed with diatomaceous earth yielded 100.7 kg of biomass. 500.6 kg of low salinomydine filtrate, which after neutralization continued for aerobic sewage treatment. The separated biomass was passed through a granulator to a fluidized bed dryer, where 68.4 kg of dry product were dried. The salinomycin content of the product is 12.8%.

Salinomycín sa využíva vo veterinárnom lekárstve ako liečivo antikokcidikum a vo výžive hospodárskych zvierat ako stimulátor rastu.Salinomycin is used as an anticoccidial drug in veterinary medicine and as a growth promoter in livestock nutrition.

Priemyselná využiteľnosťIndustrial usability

Claims (1)

1. Spôsob izolácie salinomycínu z vyfermentovanej pôdy vyznačujúci sa tým, že sa vyfermentovaná pôda upraví do kyslej oblasti pH na hodnotu 4 až 5, ďalej sa k upravenej vyfermentovanej pôde pridá inertný filtračný prostriedok s výhodou kremelina, zeolity, drevitá múčka, respektíve ich zmes, v množstve 5 až 20 % na objem vyfermentovanej pôdy, biomasa sa oddelí filtráciou a takto oddelená biomasa postupuje cez granuláciu do fluidnej sušiarne, získaný produkt sa melie a situje.Method for the isolation of salinomycin from fermented soil, characterized in that the fermented soil is adjusted to an acidic pH of 4 to 5, further comprising adding to the treated fermented soil an inert filtering agent, preferably diatomaceous earth, zeolites, wood meal or a mixture thereof, in an amount of 5 to 20% by volume of the fermented soil, the biomass is separated by filtration and the biomass thus separated is passed through granulation to a fluid-bed dryer, the product obtained is ground and sieved.
SK664-2000A 2000-05-04 2000-05-04 Method for isolation of salinomycin from the fermented soil SK283167B6 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
SK664-2000A SK283167B6 (en) 2000-05-04 2000-05-04 Method for isolation of salinomycin from the fermented soil
CZ20023429A CZ20023429A3 (en) 2000-05-04 2001-05-03 Isolation method of salinomycin from fermented soil
AU2001255144A AU2001255144A1 (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth
PCT/SK2001/000015 WO2001083801A2 (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth
DE10196144T DE10196144T1 (en) 2000-05-04 2001-05-03 Process for the isolation of salinomycin from a fermentation broth
SI200120024A SI21043A (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth
BR0110589-2A BR0110589A (en) 2000-05-04 2001-05-03 Salinomycin isolation process from fermentation broth
CA002407708A CA2407708A1 (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SK664-2000A SK283167B6 (en) 2000-05-04 2000-05-04 Method for isolation of salinomycin from the fermented soil

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SK6642000A3 true SK6642000A3 (en) 2002-01-07
SK283167B6 SK283167B6 (en) 2003-03-04

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AU (1) AU2001255144A1 (en)
BR (1) BR0110589A (en)
CA (1) CA2407708A1 (en)
CZ (1) CZ20023429A3 (en)
DE (1) DE10196144T1 (en)
SI (1) SI21043A (en)
SK (1) SK283167B6 (en)
WO (1) WO2001083801A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080003215A1 (en) * 2006-06-13 2008-01-03 Bayrock Dennis P Use of pre-dissolved pristinamycin-type and polyether ionophore type antimicrobial agents in the production of ethanol
CN108478536B (en) * 2018-03-30 2019-02-26 内蒙古拜克生物有限公司 A kind of salinomycin prilling process

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2353031C2 (en) * 1972-10-27 1985-02-21 Brevetti Gabbiani S.p.A., Podenzano, Piacenza Device for forwarding objects at an angle, in particular for processing sections of plate elements
US4009262A (en) * 1975-04-21 1977-02-22 Eli Lilly And Company Antibiotic a-28086 recovery process
JPS53148595A (en) * 1977-06-01 1978-12-25 Kaken Pharmaceut Co Ltd Preparation of salinomycines
DE3005642A1 (en) * 1980-02-15 1981-08-20 Hoechst Ag, 6000 Frankfurt SOLID OF THE SALINOMYCIN CULTURAL BROTH AND METHOD FOR ITS PRODUCTION
JPS61247398A (en) * 1986-01-21 1986-11-04 Kaken Pharmaceut Co Ltd Production of salinomycin
YU48437B (en) * 1990-12-21 1998-07-10 Hoechst Aktiengesellschaft GRANULATE OF AGRICULTURE OF BIOMASS SALINOMYCIN WHICH HAS A GOOD FLOW ABILITY, IS DUST, AND HAS AN UNLIMITED BIOLOGICAL USE OF THE ACTIVE SUBSTANCE AND PROCEDURE FOR ITS OBTAINING IT

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SK283167B6 (en) 2003-03-04
BR0110589A (en) 2003-04-01
DE10196144T1 (en) 2003-04-17
WO2001083801A3 (en) 2002-06-13
CZ20023429A3 (en) 2003-04-16
SI21043A (en) 2003-04-30
CA2407708A1 (en) 2001-11-08
WO2001083801A2 (en) 2001-11-08
AU2001255144A1 (en) 2001-11-12

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