NO131549B - - Google Patents
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- NO131549B NO131549B NO1613/71A NO161371A NO131549B NO 131549 B NO131549 B NO 131549B NO 1613/71 A NO1613/71 A NO 1613/71A NO 161371 A NO161371 A NO 161371A NO 131549 B NO131549 B NO 131549B
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- axenomycin
- culture medium
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- GYVHWLFMGIWANO-UHFFFAOYSA-N axenomycin Chemical compound C1C(O)CC(O)CC(O)CC(O)CCCC(O)C(O)C(C(C)C(O)C(C)C(O)C(C)C(O)C(C)C(O)CC)OC(=O)CC(O)C(C)C(O)CC(O)CCCC(O)CCC(C)C(O)C2(O)C(=O)OC1CC2=O GYVHWLFMGIWANO-UHFFFAOYSA-N 0.000 claims description 14
- 239000001963 growth medium Substances 0.000 claims description 12
- 230000003115 biocidal effect Effects 0.000 claims description 8
- 239000002609 medium Substances 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 241000187747 Streptomyces Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000000855 fermentation Methods 0.000 description 11
- 230000004151 fermentation Effects 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 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
- 230000000507 anthelmentic effect Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000005273 aeration Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241001464384 Hymenolepis nana Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000009655 industrial fermentation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
Fremgangsmåte ved fremstilling av et nytt Procedure for making a new one
antibiotikum, axenomycin D. antibiotic, axenomycin D.
Foreliggende oppfinnelse angår en fremgangsmåte ved fremstilling av et nytt antibiotikum. Oppfinnelsen er en videreut-vikling av norsk patentskrift 127.927 som.beskriver det antibiotiske kompleks axenomycin, de antibiotiske forbindelser axenomycin A The present invention relates to a method for the production of a new antibiotic. The invention is a further development of Norwegian patent document 127,927 which describes the antibiotic complex axenomycin, the antibiotic compounds axenomycin A
og axenomycin B og fremstilling.av disse ved dyrkning av Streptomyces lisandri under aerobe forhold. and axenomycin B and production of these by cultivating Streptomyces lysandri under aerobic conditions.
Ifolge foreliggende oppfinnelse er det nu funnet at According to the present invention, it has now been found that
ved dyrkning av Streptomyces lisandri under bestemte forhold erhol-des der et nytt antibiotikum kalt axenomycin D som har sterk tera-peutisk aktivitet. by cultivating Streptomyces lysandri under specific conditions, a new antibiotic called axenomycin D is obtained which has strong therapeutic activity.
Fremgangsmåten ifolge oppfinnelsen som omfatter dyrkning av en stamme av Streptomyces lisandri ved en temperatur fra 23 til 37°C i 60 - 160 timer ved en pH fra 6 til 9 i et vandig dyrkningsmedium inneholdende en assimilerbar nitrogenkilde, en assimilerbar carbonkilde og mineralsalter, og isoleringen ved opplosningsmiddel-ekstraksjon og kromatograf ering, er kjennetegnet ved at der anvendes et dyrkningsmedium hvis carbonkildeinnhold er lik eller storre enn 10 %, og at dyrkningen utfores ved omroring tilsvarende en absorbert kraft på 2 - 4 watt pr. liter, og med en luftstrom på fra 0,7 ti 1 2 liter pr. liter medium pr. minutt. The method according to the invention which comprises growing a strain of Streptomyces lysandri at a temperature from 23 to 37°C for 60 - 160 hours at a pH from 6 to 9 in an aqueous culture medium containing an assimilable nitrogen source, an assimilable carbon source and mineral salts, and the isolation in solvent extraction and chromatography, is characterized by the fact that a culture medium is used whose carbon source content is equal to or greater than 10%, and that the culture is carried out by stirring corresponding to an absorbed power of 2 - 4 watts per litres, and with an air flow of from 0.7 to 1 2 liters per liter of medium per minute.
Som carbonkilde kan benyttes stivelse, glucose, dextrin Starch, glucose, dextrin can be used as a carbon source
eller melasse. Som nitrogenkilde kan benyttes maisstopvæske, soya-mel, jordnottmel, kjottekstrakt, pepton, casein eller caseinhydroly-sat. Egnede mineralsalter er kalsiumcarbonat, eller natrium, kali-um, magnesium, jern, kobber, sink, mangan eller koboltklorid. Fos-fatene har ikke funnet anvendelse, da en okning i konsentrasjonen a^ disse i dyrkningsmediet minsker utbyttet av.-de antibiotiske forbindelser. Dyrkningen utfores som nevnt ; ved en temperatur fra 23 til 37°C i 60 til 160. timer ved en pH fra 6 til 9. ■ Dyrkningen kan utfores i en Erlenmeyer-kolbe eller i laboratorie- eller indu^-strielle gjæringskar av varierende stbrrelse. Når dyrkningen er over, kan axenomycin D isoleres fra mycelet, separeres fra gjærings-væsken ved ekstraksjon med et oppløsningsmiddel og renses ved kro-matografi. or molasses. As a nitrogen source, corn starch liquid, soya flour, peanut flour, meat extract, peptone, casein or casein hydrolysate can be used. Suitable mineral salts are calcium carbonate, or sodium, potassium, magnesium, iron, copper, zinc, manganese or cobalt chloride. The phos-fats have not found application, as an increase in the concentration of these in the culture medium reduces the yield of the antibiotic compounds. Cultivation is carried out as mentioned; at a temperature from 23 to 37°C for 60 to 160 hours at a pH from 6 to 9. ■ The cultivation can be carried out in an Erlenmeyer flask or in laboratory or industrial fermentation vessels of varying strength. When the cultivation is over, axenomycin D can be isolated from the mycelium, separated from the fermentation broth by extraction with a solvent and purified by chromatography.
Axenomycin D er opploselig i alkoholer, uopploselig i vann og benzen, og smelter ved 174 - 175°C med spaltning, [a]D 22 = +11 Axenomycin D is soluble in alcohols, insoluble in water and benzene, and melts at 174 - 175°C with cleavage, [a]D 22 = +11
(c = 0,5 methanol); Rf = 0,35 over silicagel (ethylacetat:Isopropanol:vann = 100:35:5). U.V. spektret i methanol har maksimum ved 250, 255 og 330 mu. og en skulder ved 265 - 268 mu-, 138 (c = 0.5 methanol); Rf = 0.35 over silica gel (ethyl acetate:isopropanol:water = 100:35:5). UV the spectrum in methanol has maxima at 250, 255 and 330 mu. and a shoulder at 265 - 268 mu-, 138
(255 mu.) . I .R. spektret viser absorpsjonsbånd ved 3440 , 2980, (255 mu.) . In .R. the spectrum shows absorption bands at 3440 , 2980,
2950, 2890, 1735,. 1705, 1675, 1630, 1610, 1465, 1385, 1355, 1290, 1265, 1195, lY70i 1115,.1080, 1050, 1005, 995, 975, 945, 925, 895, 865, 810, 700 cm<-1>.. Elementæranalyser.viser:C = 60,25 %, 2950, 2890, 1735,. 1705, 1675, 1630, 1610, 1465, 1385, 1355, 1290, 1265, 1195, lY70i 1115,.1080, 1050, 1005, 995, 975, 945, 925, 895, 865, 8010, 1010<7>cm- .. Elemental analyses.show:C = 60.25%,
H = 7,92 0 = 30,35 %. H = 7.92 0 = 30.35%.
De karakteristiske data for de tre antibiotika, The characteristic data for the three antibiotics,
axenomycin A, B og D fremgår av folgende: Axenomycin A, B and D appear from the following:
Det antibiotiske axenomycin D har en hoy antihelmintisk, antiprotozoisk og antifungal aktivitet. Den antihelmintiske aktivitet ble bestemt på mus som var eksperimentelt infisert med Hymeno-lepis nana, i grupper på 10 dyr hver. Axenomycin D ble administrert oralt mellom den 12. og 20.dag efter infeksjon. I tabell 1 er angitt prosent helbredede dyr. The antibiotic axenomycin D has a high antihelminthic, antiprotozoal and antifungal activity. The anthelmintic activity was determined on mice experimentally infected with Hymeno-lepis nana, in groups of 10 animals each. Axenomycin D was administered orally between the 12th and 20th day after infection. Table 1 shows the percentage of cured animals.
Den akutte toksisitet av axenomycin D, uttrykt som LD5Q, i mus er ca. 200 mg/kg ved oral administrasjon. The acute toxicity of axenomycin D, expressed as LD5Q, in mice is approx. 200 mg/kg by oral administration.
TA BELL 2 In vitro anthelmintisk aktivitet av axenomycin A, B og D TA BELL 2 In vitro anthelmintic activity of axenomycin A, B and D
Folgende eksempler illustrerer oppfinnelsen: The following examples illustrate the invention:
Eksempel 1 Example 1
En 2000 ml's kolbe inneholdende 500 cm 3dyrkningsmedium ble sterilisert ved 120°C i 20 minutter. Sammensetningen av dyrkningsmediet for innpodning var: A 2000 ml flask containing 500 cm 3 of culture medium was sterilized at 120°C for 20 minutes. The composition of the culture medium for inoculation was:
Kolben ble innpodet med sporesuspensjon erholdt ved vask-ning av fire 15 dager gamle skrå-agarkulturer av Streptomyces lisandri på' potet-glucose-agar-medium. Kolben ble inkubert ved 25°C i ca. 48 timer i en rotasjonsrister ved 120 omdreininger pr. minutt. 50 ml av denne kultur ble benyttet for å innpode en 5 liters glass-gjæringsbeholder inneholdende 3 liter av et medium med sararac sammensetning som ovenfor. Dyrkningsopplosningen ble omrort ved 500 omdreininger pr. minutt av to turbinplatepropeller med kurvede blad og gjennomluftet med en luftstrom på 0,7 liter pr. liter medium pr. minutt i 24 - 28 timer ved 27 - 23°C. 5 liters glass-gjæringskar, hvert inneholdende 3 liter dyrkningsmedium, ble innpodet med en mengde av forkulturen tilsvarende 5 % av volumet av det produktive medium. Sammensetningen av dyrkningsmediet i den produktive fase i hver av to tester var: The flask was inoculated with spore suspension obtained by washing four 15-day-old slant agar cultures of Streptomyces lysandri on potato-glucose-agar medium. The flask was incubated at 25°C for approx. 48 hours in a rotary shaker at 120 revolutions per minute. 50 ml of this culture was used to inoculate a 5 liter glass fermentation vessel containing 3 liters of a medium with sararac composition as above. The culture solution was stirred at 500 rpm. minute by two turbine plate propellers with curved blades and ventilated with an air flow of 0.7 liters per liter of medium per minute for 24 - 28 hours at 27 - 23°C. 5 liter glass fermentation vessels, each containing 3 liters of culture medium, were inoculated with an amount of the pre-culture corresponding to 5% of the volume of the productive medium. The composition of the culture medium in the productive phase in each of two tests was:
Dyrkningsmediet ble orarort ved 500 omdr./min ved hjelp av to turbinplatepropeller med 6 kurvede blad (absorbert kraft 3,5 watt pr. liter) med en luftstrom på 1 liter pr. liter pr. minutt. Efter 136 timers gjæring ble folgende utbytter erholdt: The culture medium was aerated at 500 rpm using two turbine plate propellers with 6 curved blades (absorbed power 3.5 watts per liter) with an air flow of 1 liter per liters per minute. After 136 hours of fermentation, the following yields were obtained:
Eksempel 2 Example 2
Dyrkningen ble utfort i 5 liters gjæringskar under de samme betingelser som i eksempel 1. Mediet i den produktive fase som inneholdt 12 % glucose, ble benyttet sammen med små mengder kalium-dihydrogenfosfat. Resultatene var: The cultivation was carried out in 5 liter fermentation vessels under the same conditions as in example 1. The medium in the productive phase containing 12% glucose was used together with small amounts of potassium dihydrogen phosphate. The results were:
Eksempel 3 Example 3
Dyrkningen ble utfort i 5 liters gjæringskar som i eksempel 1, med 12 % glucose i mediet til den produktive fase og ved 500 og 650 omdr./min (absorbert kraft 3,5 og 4,0 watt) og med luftstrøm-mer på 1 liter og 1,7 liter pr. liter pr. minutt. Folgende resul-tater ble erholdt: The cultivation was carried out in 5 liter fermentation vessels as in example 1, with 12% glucose in the medium for the productive phase and at 500 and 650 rpm (absorbed power 3.5 and 4.0 watts) and with air flows of 1 liter and 1.7 liters per liters per minute. The following results were obtained:
Eksempel h Example h
Et 80 liter's gjæringskar av rustfritt stål inneholdende An 80 liter fermentation vessel made of stainless steel containing
50 liter forkulturmedium med samme sammensetning som i eksempel 1, ble podet med 500 ml av en kultur erholdt i en 2000 ml's. kolbe som beskrevet i eksempel 1. Etter 2h timer's inkubering i gjærings-kaiet ved omroring og gjennomlufting, ble erholdt en mycelievekst tilstrekkelig til å pode et 500 liter's gjæringskar av rustfritt stål. Dette gjæringskar inneholdt 300 liter av et dyrkningsmedium med folgende sammensetning av den produktive fase: 50 liters of pre-culture medium with the same composition as in example 1 was inoculated with 500 ml of a culture obtained in a 2000 ml's. flask as described in example 1. After 2 hours' incubation in the fermentation dock by stirring and aeration, a mycelial growth sufficient to inoculate a 500 liter stainless steel fermentation vessel was obtained. This fermentation vessel contained 300 liters of a culture medium with the following composition of the productive phase:
Etter 136 timer's inkubering ved 28° C med omroringsbetin-gelser på 250 omdr./minutt av to turbinplatepropeller med 8 flate blader ( absorbert kraft 2,5 watt pr. liter) og gjennomluftning med en luftstrom på 0,7 liter/liter/minutt, med et mottrykk på 1 atmos-fære, ble det erholdt et gjæringsutbytte på 3050 y/ml. Mycelet som ble gjenvunnet ved filtrering av lk liter's kulturkraft, ble ek-strahert to ganger under omroring med h liter butanol hver gang. De kombinerte ekstrakter ble konsentrert til ca. 300 ml. Det erholdte After 136 hours of incubation at 28° C with stirring conditions of 250 rpm by two turbine plate propellers with 8 flat blades (absorbed power 2.5 watts per liter) and aeration with an air flow of 0.7 liters/liter/minute , with a back pressure of 1 atmosphere, a fermentation yield of 3050 y/ml was obtained. The mycelium, which was recovered by filtering 1 liter of culture stock, was extracted twice while stirring with 1 liter of butanol each time. The combined extracts were concentrated to approx. 300 ml. It obtained
bunnfall ble gjenvunnet ved sentrifugering, vasket med diethylether og torket under vakuum. Det derved erholdte urene produkt ble lost i methano1, små mengder uloselig produkt ble fraskilt ved filtrering, og losningen fort gjennom en kolonne av kiselsyre og eluert med ethylacetat :methanol: vann (125: 2'5:17). Under elueringen ble prover av forskjellige fraksjoner analysert ved tynnskiktkromatografi. De forste fraksjoner (ca. 2 liter av eluatet) ble fjernet. De derpå folgende fraksjoner inneholdt axenomycin D som ble gjenvunnet under vakuum ved fordampning av losningsmidlet. Ved krystallisasjon fra methanol-isopropanol ble det erholdt 7 g av produktet. precipitate was recovered by centrifugation, washed with diethyl ether and dried under vacuum. The thus obtained impure product was dissolved in methanol, small amounts of insoluble product were separated by filtration, and the solution passed through a column of silicic acid and eluted with ethyl acetate:methanol:water (125:2'5:17). During the elution, samples of different fractions were analyzed by thin-layer chromatography. The first fractions (about 2 liters of the eluate) were removed. The subsequent fractions contained axenomycin D which was recovered under vacuum by evaporation of the solvent. By crystallization from methanol-isopropanol, 7 g of the product were obtained.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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IT24144/70A IT1044819B (en) | 1970-05-04 | 1970-05-04 | ANTIBIOTIC COMPOUND |
Publications (2)
Publication Number | Publication Date |
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NO131549B true NO131549B (en) | 1975-03-10 |
NO131549C NO131549C (en) | 1975-06-18 |
Family
ID=11212205
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO1613/71A NO131549C (en) | 1970-05-04 | 1971-04-30 |
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JP (1) | JPS5422520B1 (en) |
AT (1) | AT303256B (en) |
BE (1) | BE766606R (en) |
CA (1) | CA981199A (en) |
CH (1) | CH518360A (en) |
CS (1) | CS170544B2 (en) |
DE (1) | DE2121248C3 (en) |
DK (1) | DK127559B (en) |
ES (1) | ES390826A2 (en) |
FR (1) | FR2092128B2 (en) |
GB (1) | GB1285163A (en) |
IE (1) | IE36010B1 (en) |
IT (1) | IT1044819B (en) |
NL (1) | NL153272B (en) |
NO (1) | NO131549C (en) |
SU (1) | SU377991A3 (en) |
YU (1) | YU35163B (en) |
ZA (1) | ZA712820B (en) |
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Publication number | Priority date | Publication date | Assignee | Title |
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NL153271B (en) * | 1968-06-11 | 1977-05-16 | Farmaceutici Italia | METHOD FOR PREPARING ANTIBIOTICS USING A STREPTOMYCES ORGANISM AND MEDICINAL PRODUCTS CONTAINING ANTIBIOTICS. |
-
1970
- 1970-05-04 IT IT24144/70A patent/IT1044819B/en active
-
1971
- 1971-04-20 NL NL717105286A patent/NL153272B/en unknown
- 1971-04-29 CS CS3108A patent/CS170544B2/cs unknown
- 1971-04-29 DE DE2121248A patent/DE2121248C3/en not_active Expired
- 1971-04-29 YU YU1077/71A patent/YU35163B/en unknown
- 1971-04-29 SU SU1646887A patent/SU377991A3/ru active
- 1971-04-29 IE IE537/71A patent/IE36010B1/en unknown
- 1971-04-30 NO NO1613/71A patent/NO131549C/no unknown
- 1971-04-30 AT AT373071A patent/AT303256B/en not_active IP Right Cessation
- 1971-04-30 ZA ZA712820A patent/ZA712820B/en unknown
- 1971-04-30 GB GB02382/71A patent/GB1285163A/en not_active Expired
- 1971-04-30 DK DK209371AA patent/DK127559B/en unknown
- 1971-04-30 FR FR7115543A patent/FR2092128B2/fr not_active Expired
- 1971-05-01 JP JP2937671A patent/JPS5422520B1/ja active Pending
- 1971-05-03 CH CH650871A patent/CH518360A/en not_active IP Right Cessation
- 1971-05-03 ES ES390826A patent/ES390826A2/en not_active Expired
- 1971-05-03 BE BE766606A patent/BE766606R/en active
- 1971-05-04 CA CA112,065A patent/CA981199A/en not_active Expired
Also Published As
Publication number | Publication date |
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DE2121248B2 (en) | 1978-06-22 |
FR2092128A2 (en) | 1972-01-21 |
YU35163B (en) | 1980-09-25 |
IT1044819B (en) | 1980-04-21 |
NO131549C (en) | 1975-06-18 |
IE36010B1 (en) | 1976-07-21 |
CA981199A (en) | 1976-01-06 |
SU377991A3 (en) | 1973-04-17 |
YU107771A (en) | 1980-03-15 |
AT303256B (en) | 1972-11-27 |
DE2121248C3 (en) | 1979-03-15 |
NL7105286A (en) | 1971-11-08 |
NL153272B (en) | 1977-05-16 |
DE2121248A1 (en) | 1971-11-18 |
IE36010L (en) | 1971-11-04 |
BE766606R (en) | 1971-11-03 |
DK127559B (en) | 1973-11-26 |
ZA712820B (en) | 1972-01-26 |
CH518360A (en) | 1972-01-31 |
GB1285163A (en) | 1972-08-09 |
CS170544B2 (en) | 1976-08-27 |
FR2092128B2 (en) | 1974-10-18 |
ES390826A2 (en) | 1973-06-01 |
JPS5422520B1 (en) | 1979-08-07 |
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