SK283167B6 - Method for isolation of salinomycin from the fermented soil - Google Patents

Method for isolation of salinomycin from the fermented soil Download PDF

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Publication number
SK283167B6
SK283167B6 SK664-2000A SK6642000A SK283167B6 SK 283167 B6 SK283167 B6 SK 283167B6 SK 6642000 A SK6642000 A SK 6642000A SK 283167 B6 SK283167 B6 SK 283167B6
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Slovakia
Prior art keywords
salinomycin
fermented soil
fermented
soil
biomass
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SK664-2000A
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Slovak (sk)
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SK6642000A3 (en
Inventor
Mária Jakubčová
Dušan LUCINA
Miloš Bošanský
Gabriela Borošová
Pavol IVANIČ
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Biotika, A. S.
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Priority to SK664-2000A priority Critical patent/SK283167B6/en
Priority to CA002407708A priority patent/CA2407708A1/en
Priority to PCT/SK2001/000015 priority patent/WO2001083801A2/en
Priority to AU2001255144A priority patent/AU2001255144A1/en
Priority to SI200120024A priority patent/SI21043A/en
Priority to BR0110589-2A priority patent/BR0110589A/en
Priority to DE10196144T priority patent/DE10196144T1/en
Priority to CZ20023429A priority patent/CZ20023429A3/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

Oblasť technikyTechnical field

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 (U.S. Pat. No. 4,212,942, U.S. Pat. No. 4 * 137,247).

Na 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 protispekacími 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 anti-caking agents, and can be concentrated by evaporation before drying (US 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, výhodne kremelina, zeolity, drevitá múčka, respektíve ich zmes, v množstve 5 až 20 % na hmotnosť vyfermentovanej pôdy. Biomasa sa oddelí filtráciou a postupuje cez granuláciu do fluidnej sušiarne, získaný produkt sa melie a situje.The above mentioned disadvantages are eliminated by the process of isolation of salinomycin from the fermentation broth according to the invention, which consists in that the fermented broth of salinomycin is adjusted to an acid pH range of 4 to 5. An inert filtering agent, preferably diatomaceous earth, zeolites, woody the flour or mixture thereof in an amount of 5 to 20% by weight of the fermented soil. 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, pri ktorom 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 odpadových 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 particles. The advantage is that the active substance is in the acidic pH range of the biomass cells, so that 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 than fermented soil and thus requires less energy to dry than the entire fermented soil.

Príklady uskutočnenia 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 HCI 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 filtra tu 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 meal gave 119.7 kg of biomass and 460.7 kg of a filter here with a 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 HCI 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 filtrátu 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 a filtrate with salinomycin content below 0.02%, which was discarded as in Example 1. The separated biomass was passed through a granulator to a fluid-bed dryer where drying was obtained 106.5 kg of product containing 12.1% salinomycin.

Príklad 3Example 3

Fermentačná pôda získaná fermentáciou 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 vyhnala 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 filtrátu s obsahom salinomycínu pod 0,001 %. Likvidácia filtrátu ako v príklade L Odseparovaná biomasa postupovala cez granulátor do fluidnej sušiarne, kde sa sušením získaloThe fermentation broth obtained by fermentation of Streptomyces albus had 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 driven 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 a filtrate with a salinomycin content below 0.001%. Disposal of the filtrate as in Example L The separated biomass was passed through a granulator to a fluidized bed dryer where drying was obtained.

80.7 kg produktu s obsahom 10,9 % salinomycínu.80.7 kg of the product containing 10.9% salinomycin.

Príklad 4Example 4

Fermentačná pôda získaná fermentáciou Streptomyces albus mala po 120 hod. kultivácie pH 6,3 a obsah salinomycínu 15,5 g/kg. 566,6 kg vyfermentovanej pôdy bolo upravené prídavkom 10 % HCI na hodnotu pH 4,7. K upravenej vyfermentovanej pôde sa pridala kremelina v množstve 5 % na hmotnosť vyfermentovanej pôdy. Filtráciou na rotačnom vákuovom filtri nabalenom kremelinou sa získaloThe fermentation broth obtained by fermentation of Streptomyces albus had 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 addition of 10% HCl. Kieselguhr was added to the treated fermented soil in an amount of 5% by weight of the fermented soil. Filtration on a kieselguhr rotary vacuum filter yielded

100.7 kg biomasy. 500,6 kg filtrátu s nízkym obsahom salinomycínu, 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 %.100.7 kg of biomass. 500.6 kg of low salinomycin filtrate, which after neutralization continued for aerobic waste water 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%.

Priemyselná využiteľnosťIndustrial usability

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.

Claims (1)

PATENTOVÉ NÁROKYPATENT CLAIMS 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, výhodne 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.Process for the isolation of salinomycin from fermented soil, characterized in that the fermented soil is brought to an acidic pH range of 4 to 5, further an inert filter medium, preferably diatomaceous earth, zeolites, wood meal or a mixture thereof, is added to the treated fermented soil. 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
CA002407708A CA2407708A1 (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
AU2001255144A AU2001255144A1 (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from 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
DE10196144T DE10196144T1 (en) 2000-05-04 2001-05-03 Process for the isolation of salinomycin from a fermentation broth
CZ20023429A CZ20023429A3 (en) 2000-05-04 2001-05-03 Isolation method of salinomycin from fermented soil

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

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SK664-2000A SK283167B6 (en) 2000-05-04 2000-05-04 Method for isolation of salinomycin from the fermented soil

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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
CA2655301A1 (en) * 2006-06-13 2007-12-21 Phibro Animal Health Corporation Method of reducing the growth of lactobacilli in a process of ethanol production by yeast fermentation comprising adding a pristinamycin-type antimicrobial agent and/or a polyether ionophore antimicrobial agent dissolved in an organic solvent
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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BR0110589A (en) 2003-04-01
DE10196144T1 (en) 2003-04-17
SK6642000A3 (en) 2002-01-07
AU2001255144A1 (en) 2001-11-12
WO2001083801A3 (en) 2002-06-13
WO2001083801A2 (en) 2001-11-08
SI21043A (en) 2003-04-30
CA2407708A1 (en) 2001-11-08
CZ20023429A3 (en) 2003-04-16

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