SI21043A - A method for isolating salinomycin from fermentation broth - Google Patents

A method for isolating salinomycin from fermentation broth Download PDF

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SI21043A
SI21043A SI200120024A SI200120024A SI21043A SI 21043 A SI21043 A SI 21043A SI 200120024 A SI200120024 A SI 200120024A SI 200120024 A SI200120024 A SI 200120024A SI 21043 A SI21043 A SI 21043A
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fermentation broth
salinomycin
isolating
biomass
fermentation
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SI200120024A
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Slovenian (sl)
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Maria JAKUBČOVA
Dušan LUCINA
Miloš BOŠANSK
Gabriela BOROŠOVA
Pavol IVANIČ
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Biotika A.S.
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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)
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  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • 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)
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Abstract

The present solution refers to a method of isolating salinomycin for the purpose of obtaining a granulated product. The purpose aforementioned is reached by a method for isolating salinomycin from the fermentation broth according to the invention, the nature of which consists in that the fermentation broth of salinomycin is adjusted to an acidic pH range. A suitable inert filtration aid such as diatomaceous earth, zeolites, wood flour or a mixture thereof is added in an amount of 5 to 20 wt % referred to the weight of the fermentation broth. The biomass is separated by filtration, granulated and dried in a fluid bed drier. The dry granules are ground and sieved to a required particle size.

Description

Postopek za izolacijo salinomicina iz fermentacijske brozgeProcess for isolation of salinomycin from fermentation broth

Tehnično področjeTechnical area

Predmetni izum se nanaša na postopek za izolacijo salinomicina iz pridobljene fermentacijske brozge.The present invention relates to a process for isolating salinomycin from a fermentation broth obtained.

Stanje tehnikeThe state of the art

Razpršilno sušenje fermentacijske brozge, kateri je primešano sredstvo proti aglomeraciji ter polnilo, se uporablja za pripravo salinomicina krmne kakovosti, ali pa izolirajo čisto obliko po separaciji biomase z ekstrakcijo, koncentracijo in čiščenjem surovega proizvoda s prekristalizacijo. Izolacija čiste oblike je precej zahtevna zaradi visokih proizvodnih stroškov in mehansko-tehnološke opreme proizvodne naprave (US patent 4,212,492; US patent 4,137,247).The spray drying of the fermentation broth, which is an anti-agglomerating agent and a filler, is used to prepare salinomycin feed grade, or isolate the pure form after biomass separation by extraction, concentration and purification of the crude product by recrystallization. Pure-form insulation is quite demanding due to the high production costs and mechanical and technological equipment of the production plant (US patent 4,212,492; US patent 4,137,247).

Ni potrebe po pripravi čiste oblike, če je salinomicin namenjen za uporabo kot veterinarsko zdravilo ali rastni stimulator. Po končani fermentaciji lahko obdelano brozgo direktno sušijo skupaj s primešanimi sredstvi proti aglomeraciji. Pred sušenjem lahko brozgo koncentrirajo v uparilniku (US patent 4,395,491). Pridobljena fermentacijska brozga salinomicina vsebuje mnoge stranske proizvode, ki povzročajo probleme po razpršilnem sušenju brozge. Trdne snovi aglomerirajo, tvorijo skupke ter se jih ne da dalje predelovati. Glavni razlog za tvorbo aglomeratov je vsebnost maščobe. Maščobe, vsebovane v trdni snovi, se pokažejo pretežno pri visokotemperaturni predelavi, kadar so vlažne in pod mehansko obremenitvijo. Proizvod, dobljen iz razpršilnika, je zelo prašen in ga je zato potrebno granulirati (US patent 5,529,911).There is no need to prepare a pure form if salinomycin is intended for use as a veterinary drug or growth stimulant. After fermentation is complete, the treated broth can be directly dried together with the anti-agglomerating agents. Prior to drying, the slurry may be concentrated in an evaporator (US patent 4,395,491). The salinomycin fermentation broth obtained contains many by-products that cause problems after spray drying the broth. The solids agglomerate, form clumps and cannot be further processed. The main reason for the formation of agglomerates is the fat content. The fats contained in the solids show up mainly in high-temperature processing when they are moist and under mechanical loading. The product obtained from the dispenser is very dusty and therefore needs to be granulated (US patent 5,529,911).

Granulacijski postopek je možno izvajati bodisi direktno v kombiniranem razpršilnem sušilniku z lebdečim slojem, ali pri sledeči izolacijski stopnji z uporabo metode suhe ali mokre predelave.The granulation process can be carried out either directly in a combined spray drier with a floating layer, or at the next insulation stage using a dry or wet processing method.

Ugotovljeno je, da je možno izolirati trdne snovi v obliki granul iz fermentacijske brozge salinomicina brez tvorbe aglomeratov.It has been found that it is possible to isolate granule solids from salinomycin fermentation broth without agglomerate formation.

Opis izumaDescription of the invention

Zgoraj navedene hibe odstranimo s postopkom za izolacijo salinomicina iz fermentacijske brozge v skladu s predmetnim izumom. Narava izuma je v tem, da fermentacijsko brozgo salinomicina nastavimo na kislo pH-vrednost 4 do 5. Nato dodamo primerno inertno filtrno pomožno sredstvo, kot so diatomejska zemlja, zeoliti, lesna moka ali njihove zmesi, v količini v območju od 5 do 20 mas.% glede na maso obdelovane fermentacijske brozge. Biomaso ločimo s filtracijo, zatem granuliramo in sušimo v sušilniku z lebdečim slojem. Nato granule zmeljemo in sejemo do zahtevane velikosti delcev.The above defects are removed by the process for isolating salinomycin from the fermentation broth in accordance with the present invention. The nature of the invention is that the fermentation broth of salinomycin is set to an acidic pH value of 4 to 5. Subsequently, a suitable inert filter aid, such as diatomaceous earth, zeolites, wood flour or mixtures thereof, is added in an amount in the range of 5 to 20 wt. % by weight of treated fermentation broth. The biomass is separated by filtration, then granulated and dried in a fluid bed dryer. The granules are then ground and sown to the required particle size.

Predmetna metoda zagotavlja proizvod, ki zadošča veterinarskim predpisom. To je prikladno zato, ker aktivna snov obstaja v kislem območju pH v celicah biomase in je zato možno odvajati ločeni filtrat, dobljen pri tem postopku, v napravo za biološko aerobno obdelavo odpadne vode. Nadalje je vsebina suhe snovi v tako dobljeni biomasi večja kot pa v fermentacijski brozgi, iz razloga, ker je poraba energije potrebne za sušenje biomase, nižja od porabe za sušenje celotne količine fermentacijske brozge.The method in question provides a product which meets the veterinary requirements. This is appropriate because the active substance exists in the acidic pH range in the biomass cells and it is therefore possible to discharge the separate filtrate obtained in this process to a biological aerobic wastewater treatment plant. Furthermore, the dry matter content of the biomass thus obtained is greater than that of the fermentation broth, because the energy consumption required for drying the biomass is lower than the consumption for drying the total amount of fermentation broth.

Izvedbeni primeri izumaEmbodiments of the invention

Primer 1Example 1

Fermentacijska brozga, dobljena s fermentacijo Streptomyces albus, je imela po 128 urah gojenja pH-vrednost 6,1 in vsebnost salinomicina 18,4 g/kg.The fermentation broth obtained by fermentation of Streptomyces albus had a pH value of 6.1 and a salinomycin content of 18.4 g / kg after 128 hours of cultivation.

527 kg pridobljene fermentacijske brozge smo nastavili z dodatkom 10% HCI na pH-vrednost 4,0. Obdelani fermentacijski brozgi smo dodali lesno moko (8 mas.% glede na maso obdelovane fermentacijske brozge). Z uporabo rotacijskega vakuumskega filtra, polnjenega z lesno moko, smo dobili 119,7 kg biomase in 460,7 kg filtrata, ki je vseboval manj kot 0,01% salinomicina, ter smo ga po nevtralizaciji odvedli v napravo za aerobno obdelavo odpadne vode. Odločeno biomaso smo vodili skozi granulator in sušili v sušilniku z lebdečim slojem, pri čemer smo dobili 74,2 kg proizvoda, ki je vseboval 12,3% salinomicina.527 kg of the obtained fermentation broth was adjusted by adding 10% HCl to a pH of 4.0. The treated fermentation broths were added wood flour (8% by weight by weight of the treated fermentation broth). Using a rotary vacuum filter filled with wood flour, 119.7 kg of biomass and 460.7 kg of filtrate containing less than 0.01% salinomycin were obtained and taken to an aerobic wastewater treatment plant after neutralization. The precipitated biomass was run through a granulator and dried in a fluid bed dryer, yielding 74.2 kg of product containing 12.3% salinomycin.

Primer 2Example 2

Fermentacija fermentacijske brozge s Streptomyces albus'je bila končana po 120 urah. Brozga je imela pH-vrednost 6,0 in vsebnost salinomicina 22,6 g/kg. 589 kg fermentacijske brozge smo nastavili z dodatkom 10% HCI na pH-vrednost 5,0. Dodali smo zeolit in diatomejsko zemljo ( 15 mas.% glede na maso obdelane fermentacijske brozge). Z uporabo rotacijskega vakuumskega filtra, polnjenega z diatomejsko zemljo, smo dobili 184,7 kg biomase in 495,6 kg filtrata, ki je vseboval manj kot 0,02% salinomicina, ter smo ga odvedli kot pri Primeru 1. Odločeno biomaso smo vodili skozi granulator in sušili v sušilniku z lebdečim slojem, pri čemer smo dobili 106,5 kg proizvoda, kije vseboval 12,1% salinomicina.Fermentation of the fermentation broth with Streptomyces albus was complete after 120 hours. The broth had a pH value of 6.0 and a salinomycin content of 22.6 g / kg. The 589 kg fermentation broth was adjusted by adding 10% HCl to a pH of 5.0. Zeolite and diatomaceous earth (15 wt.% By weight of treated fermentation broth) were added. Using a rotary vacuum filter filled with diatomaceous earth, 184.7 kg of biomass and 495.6 kg of filtrate containing less than 0.02% salinomycin were obtained and taken as in Example 1. The decomposed biomass was passed through granulator and dried in a fluid bed dryer, yielding 106.5 kg of product containing 12.1% salinomycin.

Primer 3Example 3

Fermentacijska brozga, dobljena s fermentacijo Streptomyces albus, je imela po 124 urah fermentacije pH-vrednost 6,2 in je vsebovala 17,1 g/kg salinomicina. Z dodatkom raztopine NaOH je bila dosežena pH-vrednost 7 do 8.The fermentation broth obtained by fermentation of Streptomyces albus had a pH value of 6.2 after 124 hours of fermentation and contained 17.1 g / kg salinomycin. A pH of 7 to 8 was obtained by the addition of NaOH solution.

Tako obdelano fermentacijsko brozgo smo segreli na temperaturo 60 °C in po ohlajenju smo nastavili pH-vrednost z razredčeno HCI kot pri Primeru 1. Dodali smo zeolit ( 20 mas.% glede na maso fermentacijske brozge) k 524 kg obdelane fermentacijske brozge. Zmes smo filtrirali skozi sloj diatomejske zemlje kot filtrnega pomožnega sredstva z uporabo rotacijskega vakuumskega filtra in smo dobili 184,7 kg biomase in 495,6 kg filtrata, ki je vseboval manj kot 0,001% salinomicina. Filtrat smo odvedli kot pri Primeru 1. Odločeno biomaso smo vodili skozi granulator in sušili v sušilniku z lebdečim slojem, pri čemer smo dobili 80,7 kg proizvoda, ki je vseboval 10,9% salinomicina.The fermentation broth thus treated was heated to 60 ° C and, after cooling, the pH was adjusted with dilute HCl as in Example 1. The zeolite (20 wt% by weight of fermentation broth) was added to 524 kg of treated fermentation broth. The mixture was filtered through a layer of diatomaceous earth as a filter aid using a rotary vacuum filter to obtain 184.7 kg of biomass and 495.6 kg of filtrate containing less than 0.001% salinomycin. The filtrate was removed as in Example 1. The precipitated biomass was run through a granulator and dried in a drier-dryer, yielding 80.7 kg of product containing 10.9% salinomycin.

Primer 4Example 4

Fermentacijska brozga, dobljena s fermentacijo s Streptomyces albus, je imela po 128 urah fermentacije pH-vrednost 6,3 in vsebnost salinomicina 15,5 g/kg. 566,6 kg fermentacijske brozge smo nastavili z dodatkom 10% HCI na pH-vrednost 4,7. Obdelovani fermentacijski brozgi smo dodali diatomejsko zemljo (5 mas.% glede na maso fermentacijske brozge). Uporabili smo rotacijski vakuumski filter napolnjen z diatomejsko zemljo. Dobili smo 100,7 kg biomase in 500,6 kg filtrata, z nizko vsebnostjo salinomicina, ki smo ga po nevtralizaciji odvedli v napravo za aerobno obdelavo odpadne vode. Odločeno biomaso smo nato predelali z granulacijo, sušili v sušilniku z lebdečim slojem, pri čemer smo dobili 68,4 kg suhega proizvoda, ki je vseboval 12,8 % salinomicina.The fermentation broth obtained by fermentation with Streptomyces albus had a pH value of 6.3 and a salinomycin content of 15.5 g / kg after 128 hours of fermentation. The 566.6 kg fermentation broth was adjusted by adding 10% HCl to a pH of 4.7. Diatomaceous earth (5 wt.% By weight of fermentation broth) was added to the treated fermentation broths. A rotary vacuum filter filled with diatomaceous earth was used. We obtained 100.7 kg of biomass and 500.6 kg of filtrate, low in salinomycin, which after neutralization was taken to an aerobic wastewater treatment plant. The recovered biomass was then processed by granulation, dried in a fluid bed dryer, yielding 68.4 kg of dry product containing 12.8% salinomycin.

Industrijska uporabnostIndustrial applicability

Salinomicin se uporablja v veterinarski medicini kot kokcidiostat (proti Coccidium) in kot rastni stimulator v živinoreji.Salinomycin is used in veterinary medicine as a coccidiostat (against Coccidium) and as a growth stimulant in animal husbandry.

Claims (1)

Patentni zahtevekPatent claim Postopek za izolacijo salinomicina iz fermentacijske brozge, značilen po tem, da fermentacijsko brozgo nastavimo na kislo pH-vrednost 4 do 5, fermentacijski brozgi dodamo primerna inertna filtrna pomožna sredstva, kot so diatomejska zemlja, zeoliti, lesna moka ali njihove zmesi v količini 5 do 20 mas.% glede na maso fermentacijske brozge, biomaso odločimo s filtracijo, granuliramo in nato sušimo v sušilniku z lebdečim slojem, dobljene suhe granule pa zmeljemo in sejemo na zahtevano velikost delcev.Process for isolating salinomycin from fermentation broth, characterized in that the fermentation broth is set to an acidic pH value of 4 to 5, suitable inert filter aids such as diatomaceous earth, zeolites, wood flour or mixtures thereof in the amount of 5 to 5 are added to the fermentation broth. 20% by weight based on the weight of the fermentation broth, the biomass is determined by filtration, granulated and then dried in a fluid bed dryer, and the obtained dry granules are ground and sown to the required particle size.
SI200120024A 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth SI21043A (en)

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SK664-2000A SK283167B6 (en) 2000-05-04 2000-05-04 Method for isolation of salinomycin from the fermented soil
PCT/SK2001/000015 WO2001083801A2 (en) 2000-05-04 2001-05-03 A method for isolating salinomycin from fermentation broth

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BR (1) BR0110589A (en)
CA (1) CA2407708A1 (en)
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DE (1) DE10196144T1 (en)
SI (1) SI21043A (en)
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BRPI0713409A2 (en) * 2006-06-13 2012-03-27 Phibro Animal Health Corporation method of controlling metabolism of paste lactobacilli in an ethanol production facility; method of eradicating lactobacilli paste in an ethanol production facility; and method of controlling unwanted microorganisms in pulp in an ethanol production facility
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

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* Cited by examiner, † Cited by third party
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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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CA2407708A1 (en) 2001-11-08
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BR0110589A (en) 2003-04-01
SK6642000A3 (en) 2002-01-07
DE10196144T1 (en) 2003-04-17
AU2001255144A1 (en) 2001-11-12
SK283167B6 (en) 2003-03-04
CZ20023429A3 (en) 2003-04-16

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