CS258001B1 - Method of ergotamine production - Google Patents
Method of ergotamine production Download PDFInfo
- Publication number
- CS258001B1 CS258001B1 CS794080A CS794080A CS258001B1 CS 258001 B1 CS258001 B1 CS 258001B1 CS 794080 A CS794080 A CS 794080A CS 794080 A CS794080 A CS 794080A CS 258001 B1 CS258001 B1 CS 258001B1
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- CS
- Czechoslovakia
- Prior art keywords
- ergotamine
- tul
- production
- ibp
- lav lav
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- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 title claims 4
- 229960004943 ergotamine Drugs 0.000 title claims 4
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 title claims 4
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 238000000034 method Methods 0.000 title claims 2
- HEEACTTWORLLPM-UHFFFAOYSA-N 2-(1h-imidazol-5-yl)ethanol Chemical compound OCCC1=CNC=N1 HEEACTTWORLLPM-UHFFFAOYSA-N 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical class N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical class [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 238000010564 aerobic fermentation Methods 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 229910052500 inorganic mineral Chemical class 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000002609 medium Substances 0.000 claims 1
- 239000011707 mineral Chemical class 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 241000221751 Claviceps purpurea Species 0.000 description 5
- 241000221760 Claviceps Species 0.000 description 2
- XGZRAKBCYZIBKP-UHFFFAOYSA-L disodium;dihydroxide Chemical compound [OH-].[OH-].[Na+].[Na+] XGZRAKBCYZIBKP-UHFFFAOYSA-L 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 241000368779 Asota Species 0.000 description 1
- 101100120289 Drosophila melanogaster Flo1 gene Proteins 0.000 description 1
- 229910005390 FeSO4-7H2O Inorganic materials 0.000 description 1
- 229910005444 FeSO4—7H2O Inorganic materials 0.000 description 1
- 101150096418 Mepe gene Proteins 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
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- Crystals, And After-Treatments Of Crystals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
J HA3BAHHE H30EPETEHHflCnocoO nonyMeHHH sproTaMHHaOGíiaCTb ΠΡΗΜΘΗΘΗΗΗ Η3θ6ρβΤβΗΗΗ ΗβοδρβτβΗΗβ KacaeTca cnocoGa nonyHeHHH sproTaMHHa.
CpeflH. Bfcinie 50 λο chx nop HSBecTHux πρηροαηηχ anxanoHflOB cjiopmhh npeACTaBHTe-JIH ΠβΠΤΗβΗΟή rpynntl HM6I0T Oonbtnoe 3HaWeHHe B MeAHUHHe. Han8onee H3BeCTHb!MHnpeflCTaBHTejIHMH HBJIHIOTCH aprOTaMHH, aprOKOPHHH, SprOKpHnTHM H ŠprOKpHCTHH, , OproTaMWi npexfle Bcero noBumaeT AaBjienne xpoBH, ycmiHBaeT n ycKopxeT koht-paKium mhtkh h bjihhmt Ha τορΜοχβΗΗβ aApeH3prHvecxHx HepBHbtx bojiokoh. 3prora-mhh ripuMenaeTCH b rHHexonorHH.h Tepánu». Hapany c sthm cymecTeyeT bo3mo«-hoctb aacTHHHo-cHHTeTHMecKoro M3MeHeHHB ocoĎeHHo pfin noncKa hobmx noxaaaHHň. f .
XapaKTepHCTHxa HSBecTHbix TexHHvecxHX pemeHHň B HacToamee BpeMH tph cnocoGa onpeflejijnoT ypoeeHb TexHHKH canpo<J>HTHvecxorononyveHHH sproTaMHHa.
IttraMM Claviceps purpúrea (Fr.) Tul, ATCC 15383 oGpaayeT 900-1450 μκγ 3pro-TaMHHa Ha mji cycneiismi xynbTypu,
AnKanoHflbí (sproTaMHH; 3proTaMHHHH) xax npH stom cnocoGe, Tax η npH ocTanb-Hbix oCcyxnaeMbK cnocoGax HaxoflHTCH xax h b cycneHSHH· xynbTypw, Tak h b mh-uejine (DE-AS 1 210 128), ΠρΗ flpyroM cnocoGe c πομοπιβιο nrraMMa Claviceps purpurea FI 32/17 oCpasyeTCflCMecb anxajioHAOB na sproTaMHHa η βργοκρηπτηηβ ηπη hx HSOMepos 3ργοτβμηηηη3h aproxpunTHHHHa b xojnraecTBax ot 1200 ao 3800 μκγ anxanoHAa Ha ηπ cycneH-3hh xyjibTypu, npHveM o6a anxaJioHAa oGpasoBajiHCb b npHGjuoHTenbHo OAHHaxoBuxxojiHHecTBax (DE-OS 1 792' 038), ΙΙΙτβΜΜ Claviceps purpurea OKI 56/70 oGpaayeT . b canpotfiHTHHecxoft xynbType Me«-
Ay 1300 η 1850 μκγ anxanoHAOB Ha mji cycneHSHH KynbTypw, cpeAH xotopmx 80% cocTaBJiHK»T sproTaMHH/aproTakHHHH (BeHrepcxHň naTeíiT 161 654). 258001 2
Bce cnocofibi ΗΜβιοτ tot ιιε,ηοοτβτοκ, ντο fljiH BbifleneHHH ajiKanoHflOB Ha«o o6pa6a-TUBaTb Bcm cycneH3Hio KyjibTypbi. B Heo6xoflHMOcTH 3KCTpaKimn anKanoHflOB Kax hsnHTaTeíibHoň cpe^u, Tax h H3 MHyenn aaxnmaeTCB TexHMvecKHň Ηβ,ςοοτβτοκ 3thxcnoco6oB. Bo ΒτοροΜ H3 HasBaHHbix cnocoSoB HMeeTca eme o^hh Ηβ,ροοτβτοκ - Ha-níme AByx poflCTBenHbix nermmuwx anKanoHHOB, aproTaMHH η βργοκρηπτηη, b OflU“HaxoBbix xojnraecTBax, Tax ντο HeoĎxoflHMo ncnojib3OBaTb TpyjjoeMKne cnoco6bi pa3-fleneHHH.
Uejib Η3ο6ρετβΗΗΗ
Uejibio H3o6peTenna HBnaeTca^ nonyueHHe anKanoHfla aproTaMHHa no BbiroflHOMycnocoCy h TaxHM o6pa3OM eró npeflocTaBnenne pjin ycnneHHoro ηρΗΜβΗβΗΗΗ b Me-AHitHHe. H3JI0«eHHe CymHOCTH Η3θ6ρβΤβΗΗΛ B ocHOBy Η3ο6ρβτεΗΗΗ nonojKeHa sanana. paaBHTb cnocoC nonyneHna sproTaMHHa,npn κοτοροΜ BbwenenHe ajucajionfla ocymécTBJíHeTca τοηβκο «3 nHTaTejibHOň cpeflbíh KOTopbiň ne TpeSyeT TpyfloeMKoro OTfleneHHa poflCTBeHHbix πβπτΗΑΗΜΧ ajiKanoH-AOB. Pflst 3Toro Hago BbmejinTb tnTaMMbi, KOTOpbie: 1 . B COCTOHHHH lf CanpO<J)HTHVeCKH O6pa3OBaTb 3prOT3MHH, KOTOpblíi ΠΟΗΤΗ CBO·SofleH ot noSouHbix βηκβηοΗβΟΒ nenTHflHoň rpynnbl, 2, o6pa3OBaBniHecH ajiKanoHflbí BbwejiHWT b oRpyTKaramyio nnTaTenbHyioe cpeny Sonb-me ueM Ha 95%, 3. OTJnwaioTCH CTaSunbuocTbio, xopomefl npoflyKHHeň ajmcajioHgoB m SnaronpŘHT-HblMH CBOflcTBBMH φβρΜβΗΤβμΗΗ. • CornacHo Η3θ6ρβτβΗΗΚ> pjin npoH3BOflCTBa 3proTaMHHa Hcnojib3yeTCH niTaMM Clavi-ceps purpuréa (Fr.) Tul. IBP 74, ero MyTaHTbi hjih β3ρηβητμ·
Ho b bifl ηιτβΜΜ Claviceps pUrpurea (Fr.) Tul. IBP 74 no« Η33βηηη@μ IMET PA 135nenoHHpOBan b UenTpaJibHOM HHCTHTyTe mhkpoShojiothh h 3KcnepHMeHTanbH‘oň Tepa-πηη AKafleMHH Hayx ΓβΡ b ňene. Oh oSpaayeT oSmyro cMecb anKanoHfloB (πρη6πη3Η-TenbHO 900 - 1500 μκγ Ha mji KyjibTypHoro pacTBopa), H3 κοτοροϋ Ηβ MeHbme50% anKajioHflOB BbrrpHXHBaeMbi b opraHHvecKHň pacTBopHTejib, H3 κοτορωχ Sojiee75 “ 80% COCTHBJIHeT napa H3OMepOB-3prOTaMHH/3prOTaMHHHH.
Kax conyTCTByronme anxajioHflbí b CMecu coflepxcaTca:
XaHOKJiaBHH 10—15% BbrrpaXHBaeMoň flOJiH aproMeTpHH 5-6% 3ΡΓΟ3ΗΗ CJieflbl 4% 3ΡΓΟΚΡΗΠΤΗΗ 5% flpyrne KjiaBHHbí vacTHUHo cjieflu. B nnTaTejibHbix cpeflax ocTaeTcn nocne βμτρηχηβηηηη cpeflu flpyrnx h nuseprmtOBanKHcnoTa. Ha nuTaTenhHbix pacTBopoB ajiKajioHgbi H3OJiHpyroTCH ηββθοτηημ nyTeM.Bosmowho npeepamenHe ofliioro anKajioHflHoro H3OMepa b npyroft.
HoBbiň ιπτβΜΜ oTJiHuaeTca TeM, ντο oh flaeT 6ojibme 95% o6pa3OBaHHhix ajixajioHflOBb oKpyxcawmyK) nHTaTejibiiyio cpejjy h conyrcTBywiHHe ajixanoHflbí Jierxo OTflejineMbi,
í KyJibTHBaipHO fljin xapaxTepHCTHKH Claviceps purpuréa (Fr.) Tul. IBP 74, IMET PA 135 npoBOflHJiH na hjih b cpe^ax, npHBefleHHbixvB . TaSjínue 1. HoBbrit πιτβμμ ημθ- βτ cJieflyranHe MaxpocKonHvecKHe h MHKpocKonHvecKHe ceoflcTBa: 258001 3
MaKpocKontraecKHft buk: BO3pacT KyjibTyp:arap NL 126: arap NL 829: 3 Helenu nnoCKHň,CBeTnO“KopHHHeBblft ΠΟΚΡΟΒ, nyWHCTbtíi, KOpHH“HeBbift, CKJiafl^íaTbiň; oTflenbHbie kojiohhh: (6 0,8-1,3 cm, οστρο orpaHHweH-ΗΜβ,ϋΒβΤΠΟ-ΚΟρΗΗΗβΒΜβ, nymHCTwe.
CnaQan guiioopecHeHiiHH b yxibTpa4>HoneTOBOM CBere. MOJHHMň, CHHbltO CKJiaflHaTblft ΠΟΚΡΟΒ,
BepxHHn eropoHa cépo-KopHHHeBaa,οοτρο orpamweH-Hbtň Kpaft. OTflenbHbie kojiohhh: ¢( 0,8-1,3 cm, bmcotb no 1 cm.KoHycoBHAHbie, ocTpo orpaHHqeHHbie,
BepxHHH cTopona cepo-KopH«tHeBaa, ,· ttnxHaa eropoHa: Mono^ue kojiohhh «βπτο-κορΗΗΗβΒΜβ^ crapbie kojiohhh cpeflHe-KOHHHHeBbie., «bnioopecueHijHH b ΥΦ-οββτβ. MHKpOCKQIHWeCKHft BHflj ΠβρΒΗΗΗβΗ KynbTypa NL 849:
BoapacT 3 ρρχ . - οτηοοητβπβηο κοροτκκβ, cwibHo pasBeTBJteHHbie ΓΗ(>1. Γκφω 6onee ηπη MeHee CHuibHo paapeneHHbie, cnnbHosepHHCTbie, 3epHncTbie c nyabipqaTbiMH yronmeHHííMH,oTflenbHbie apTpocnopw. flnHHa γηΦοβ 50-200 μκγ, ny-3bipnaTbie yTonmeHHH 10 mkm.
PnaBHaa KynbTypa NL 833:
BoapacT 7 flHeň - Mrajenna c ajihhhwmh', pasBeTBJíeHHWMHi γηΦβμη. CTeH-
Ka γηΦοβ HopMajibHaa, He ocoCeHHÓ BbiflejiHiomaaca,pa3fleJieHHaH,: ΓηΦμ "aepHHCTwe". iinasMa ueHTpajibHaH ηπη npHCTeHOMHaa.
Ilyswp.HaTbie yTonmeHHH name Bcero y kohijob γηΦοβ.OTAenbHhie cnopw/xnaMHflo-HnH apTpocnopw/, 0- γη-Φοβ: 5-7 mkm, <t> ny3bipMaTbtx yTonmeHHii: 8-10 mkm,
Bo3pacT l4 flHeň - MHpenna c απηηημμη, pasBeTBneHHWMH γηΦβμη, cHntb- ho pa3flejieHHbie. ILnaaMa peHTpanbHaH hjih npHCTeHOHHaH· & γηΦοβ: 5-7 mkm
IlysupnaTbie yTOjiqeHHH 8-12 mkm. OTAejibHbie apTpocnopbi.
Mnnenna coflepatHT nHnHniibie KanjiH, flojia KOTopwx ocoóeHHo BbicoKa b KyjihTypax,oCpaaywniHX anKanoHflw. 1
KyjibTHBaiXHio npoBoflHHH npH 24íl°C. KyjibTypw HHKyCHpoBajiH Ha Kpyrnwx BCTpHXH-iBaranHxcH cTOjiax řípu 24.0 o6/mhh.
Uejiecoo6pa3HO npoBopHTb aapoOHyio φβρΜβΗτβμκιο rpnCKa ajih nponsBOflCTBa b jkha- khx nHTaTejibHbix cpeflax b noBepxHocTHoň h/hjih rny0HHHoň KyjibType. IlHTaTenbHwe cpepw coflepxcaT ycBoaeMbiň hctomhhk yrnepona, κβκ HanpHMep caxaposy, rnioKosy,
MaHHHT, COp0HT, ΓΠΗΙΙβρΗΗ, JIHMOHHyiO HJIH HHTapHy» KHCJIOTbl} yCBOHeMWft HCTOHHHK asoTa, xax HanpHMep 3μμηηκ,' . acnaparnH, πθπτοη, rHaponnaaT xaseHHa ηπη conn 258001 βμμοηηη, a TaKwe MHHepaAbHbie cojih, ΦερΜβΗτβΑΗΐο mojkho npoBOAHTb b xonOax4>epH6axa, EpneHMeňepa, nnocKOflOHHbix xon6ax hah b φβρΜβΗΤορβ.
UenecooOpasHo npoBOAHTb φβρΜβΗτβΑΗΐο b ’οαηοΠ ao Tpex , CTyneHeň. Βμγοαηο ecAHnepBiPtHaH xynbTypa ΗΜββτ BO3pacT ot 4 po 14. ppeň, ň npHBHBOHHoe cooTHonteMuenepBHHHoň xyjibTypu: rjiaBHoft xynbTypbi ρβΒΗΗβτβπ 1:5 po 1:20, Γααβηηη xyjibTy-pa BbtaepxHBaeTca 7-20 AHeň. 3havenue pH Μοχβτ xojie6aTbc« Μβ»ΑΥ 4,0 h 6,2, aTeMnepaTypa Me»Ay 20 h 30°C. OnTHMaAbHoň ΗΒΑΗβτβΗ φβρΜβΗτβΑΗΗ npH 22-25°Ch pH » 5,2-5,9. A . UIthmm coxpaHHeTCH οΘμηηΜμ cnocoCoM c noMombio προβκροκ, ηπη xynbTHBaiXHH προτο-nnačTOB hah xpaHeHHGM npH hhskhx TeMnepaTypax επρΗΜβκβΗΗβΜ saotHTHbtx koaaoh-Aob, xax HanpHMep 60% pacTBopa caxaposbi: cHHToe moaoko 2:1. ΠρΗΜβρΜ OCymeCTBneHHft H3O6peTeHHH .
CoeffytoiQHe ηρΗΜβρω πρηβοαητch c nenbio ο6έηοηθηηη η3ο6ρθτθηηη.
KcnonbsoBaHHbie nHTaTenbHbie pacTBopu πρκΒβΑβΗΗ b τββπΗΑβ 1,
I ΠρΗΜβρ 1:
Hcxoah H3 KOHcepBOB nrraMMa Clavícepe purpuřea (Fr.) Tul. IBP 74 aaceanH nep-BHHHbie xynbTypbi b 100 μπ cpeAbt NL 849 b nnocKOAOHHbix KonCax Ha 500 ma. Koa-6m BbiAepKHBanHCb 7 AHeň πρκ TeMnepaType 24+1°C h 240 o6/mhh. 10% ot nony-neHHbix xyjibTyp cnyxcHno aah τογο, Ητοβω aaceHTb κοπ6η Ha 500 ma c 100 ma cpe-AM NL 833 b xaKAoft· ílocne 14 ppeft HHKyOauHH npH onHcaHHbix ycnoBHHX KynbTypwcoAepatanH 1450 μκγ/μπ. anKanoHAa KynbTypHoro patíTBopa BbnneHaSBaHHoro cocTaBa.ΠρΗΜβρ 2:
Hcxoah H3 HaaBaHHoň b npHMepe lt nepBHHHoň KynbTypbi b NL 849 aaceanH BTopyionepBHAHyio xyAbTypy b Ty κβ cpeAý. Η b stot paa npHBHBOHHoe cooTHomeHHe coc-TaBHAO 1:10. ΠοβΑβ 7 AHeň KynbTHBHpoBaHHH pasBOAKAH HHKySauHOHHbiň MaTepHanΗ ΠρΗΒΗΒ3ΑΗ ΑΠΗ HHKy6HpOBaHHH φβρΜβΗΤΟρβ C 2,0 A NL 833 B βΟΟΤΗΟΠΙβΗΗΗ 1:103THMH BTOpHHHblMH ΠρβΑΒβρΗΤβΑΒΗΗΜΗ KyAfcTypaMH.
TeMnepaTypa 24°C
CxopocTb nepeMeuiHBaHHH: 280-450 o6/mhh., KoneSneTCH no pone npHpocTa. Ποτοκ BO3Ayxa: 0,2-0,65 a/mhh., b aaBHCHMocTH οτ παοτηοοτη.BMpocmeň MHAennbi. Ποοπβ 12 A«eň o6pa3OBanocb 900 μκγ oS^ero anKanoHAa Ha ma xynbTypHoro pacT-sopa. ΠρΗΜβρ 3: fljIH ΗΑβΉΤΗφΗΚβΑΗΗ aAKHAOHAOB ΠΟΑΠξβΛβΑΗΒβΙΟΤ 1 “5 MA ΠΗΤβΤβΑΒΗΟΓΟ paCTBOpa ΗτρΗ pasa SKCTparHpyioT χηοροφορΜΟΜ. 3κοτρβκτ BbicymHBawT, αο6ββπηιοτ Manoe Ko-AHuecTBO χποροφορΜΗ η ρ33ΑβΑΗΐοτ· c noMombio npenapaTHBHOň CAoňnoň xpoMaTofpa-|Φηη Ha cHAHKarene c φΑίοορβεηβΗΤΗΜΜΗ HHAHKaTopaMH. B xanecTBe cncTeMbi pacT-BopHTeneň ynoTpeSnnioT χηοροφορΜ: sthhoa (9:1). AnKanoHAHbie 3ohm CHHMaiOT cnAacTHHKH h npHHHMawTCH CMecbw boam:MeTaHOAa:AeAHHoň yxcycHoň khcaotm(45:45:10), ομθιπηβηκτ c peaxTHBOM βηη Ypxa b οοοτηοπιθηηη 2:4 h oSnyvawT'xBapAeBoň AaMnoň b TeneHHe 5 MHHyT, ΑβΗτρΗφνΓΗρνιοτ η οπρβΑβΑΗΐοτ skcthhkahw .B φΟΤΟΜβΤρβ, KOAHHeCTBO 3ΑΚ3ΛΟΗΑθΒ ΟΠρβΑβΑΗΙΟΤ ΠΟ KaAHČpOBOMHblM KpHBblM. H3napaAAeAbHbtx npo6 npenapaTHBHOň CAoňHoň χροΜβτοΓρβφΗΗ moucho οταθαβηο bmmm—BaTb npnnHcaHHbie aproTaMHHy hah sproTaMHHHHy 3OHbi h noAaBaTb· hx απη α^ΠΒ-Heňmeň ΗΑβΗΤΗφΗκβΑΗΗ. Οοο6θηηο ποαχοαητ: 258001 5
Macc-cneicrpoMeTpHa (m)e: 581 (M+), 314, 296, 286, 271, 267, 244, 223, 221,215, 180, 167, 153, 131, 125, ΪΦ-, HK- h ΗΜΡ-αιεκτροεκοηΗΗ, χροΜβτοΓρβφκ-uecKHe MeTOAbi, a Taxxe KHCJibiň rHflpojiHs h AOxasaTenbCTBO xapaxTepHUX hmhho-KHCJIOT “ npOJIHH Η (fceHHJiajiaHHH . řípu meJIOMHOM ΓΗΑΡΟΠΗ3β MOXHO flOKa3aTb ΗβΛΗ-ΗΗβ JIHSeprHHOBOft KHCJIOTbl (H9 SprOTaMHHa) ΚΠΗ H3OJIH9eprHHOBOft KHCJIOTbl («3
SprOTaMHHHBia) .
Ta0jinqa 1: Coctsb HCnonbsyeMMX πκτβτβπΒΗΜΧ cpejn (tfaHHbie b γ/λ) - ----η. NL 849 | NL 720 j NL 833 | NL 126 | NL 829 Caxaposa 300,0 200,0 300,0 100,0 CHHTOe MOJI OK o 100 mji - * - - nHBHoe cycno i - - - 150 Mn - AHTpaT aMMOHHB 10,0 15,0 20,0 1,0 acnapariiH - - 10,0 . ΑΡΟΧΧβΒΟΑ BKCTp. - - 5,0 0,5 Ca(NO,)2 - i,o 1*0 - 1,0 KH,PO4 0,25 0,25 0,25 - 0,25 (ΝΗ4),ΗΡ0+ i - - - 5,0 - MgSO4·7H,0 , 0,8 0,3 0,3 0,25 FeSO4-7H2O 0,01 0,01 - 0,02 ZnS04.7H.,0 •M 0,0308 0,0308 - 0,02 KC1 0,1 - - flHCT. BO«a Pfi 1 ji 1 n 1 JI 1 ji 1 Ji arap-arap - - - 30,0 30,0 pH nepea cTepHJiHsaijKeft 5,4 5,8-6,0 5,4 6,0 5,4 ··. ycTaHOBxa pH c nOMombw NaOH NaOH NaOH NaOH NaOH - aBTOKjiaBupoBaHHe Anta Bcex cpefl 30 MHHyt ttpH 110"C Ta&nmja4 1: Coctqb HcnonbsyeMbix nHTaTejibHbix cpen (aarnibie b r «a ji) ___________________] NL0** | NL | NLM | Ní?16 | NL**5
Caxaposa 300,0 200,0 300,0 - 100,1 CHíITOe MOJIOKO 100 mji · - - , - nHBHoe cyeno - - - 150 mji - HHTpaT 8MMOHHH 10,0 15,0 20,0 1,0 - acnaparuH - «Μ ! - - - 10,0 Apoxxesoň 3KCTp. - • i. - · ' 5,0 0,5 HHTpaT KaJIbHHH - 1,0 1,0 - 1,0 ΑΗΓΗβρΟΓβΗφοέφβΤ KaJIHH 0,25 0,25 0,25 - ,· 0,25 ΓΗΑρΟΓΘΗφοεφβΤ aMMOHHH - - - 5,0 ΟΤΠΒφβΤ ΜΒΓΗΗΗ (7 HiP) 0,8' . 0,3 0,3 a» 0,25 ογ/ΐΒφβτ xenesa (7 Η-χΟ) - 0,01 0,01 - 0,02 ογπΒφβτ uHHxa (7 H^O) - 0,0308 0,0308 - 0,02 ΧΠΟΡΗΑ KQJIHH _ - 0,1 - - - AHCT. BOfla flO 1 ji 1 ji 1 ji 1 ji 1 ji arap-arap - 30,0 30,0 pH nepefl cTepHJiHsauHefl 5, V 5,8-6,0 5,4 6,0 5,4 ycraHOBKa pH C ΠΟΜΟΠφΙΟ ΗβΤρΗβΒΟΟ ntanotiH» aBTOKJiaBHpoBaHHe AJiH Bcex cpefl 30 mhh npH 110 C 258001
(PopMyjia HsoCpeTeHHH 1. Cnoco6 npoHSBOflcTBa aproTaMHHa, oTJiHwaionmňCH τβΜ, ντο nrraMM Clavicepspurpurea (Fr.) Tul. IBP 74, IMET PA 135, ero. MyTaHTbi h BapnaiiTbi, KynbTM-BHpywT nyTeM aapotitioft φβρΜεΗτβηΗΗ b «ηηκοή nHTaTenbHoft cpene, κοτορεπcoflep»ijT ycBOBeMbiň hctovhhk ymepofla, a3OTa h MHHepajibHbix coneň, b no- , BepxHocTHoň h/hjih rnyOHHHoft KynbType npw TeMnepaType 20-30°C κ SHaveHHHpH 4,0 flo 6,2 b τβΜβΗΗβ οτ 7 no 35 flHefl h oCpaaoBaHHbiň sproTaMHH/aproTa-MHHHH HBOJIHpyeTCH H3 nHTaTeJIbHOft CpenbI HSBeCTHblM nyTeM. 2. Cnocoč no nynKTy 1, OTjiinawmHňcH τβΜ, ντο φβρΜεΗτβιχΗΗ npoBOflHTCH npn
TeMnepaType 22 n° 25°C h 3HaveHHH pH ot 5,2 po 5,9, AHHOTAfflg
OnucbiBaeTCB nonyneHne ajiKanonna sproTaMHHa c noMombio nrraMMa Claviceps purpu-rea (Fr.) Tul, IBP 74, IMET PA 135, ero MyTaHTOB h BapnaHTOB, 3tot HOBbiň mTaMM oSpaayeT CMecb ajiKanonflOB ot 900-1500 μκγ Ha μπ ηκτβτβΠΒΗΟ-ro pacTBopa, οτ κοτοροή no κρβήΗβή Mepe 50? ajiKanonflOB BbiTpaxHBaeMbi opraHH-VeCKHMH paCTBOpHTeJIHMH. Πομημο 3proTaMMHa ηπη ero HáOMepa sproTaMHHHHa (BMecTe 6ojiee 75-80? nonyvae-μογο ajiKanoHffa) oOpaayioTCH h xaHOKJiaBHH (10-15?), sproMeTpHH (5-6?), apro-3HH (cneflM - MHKCHMyM 4?), aprOKpHnTHH (5?), ΠΡΗ cnyvae H npyrtie ΚΠβΒΗΗΜ BoveHb Manbix KOJiHnecTBax (cnenw). B nHTaTenbHoň cpene HaxoflHTCH H JiHaeprHHO-ΒβΗ KHCJIOTa,
UlTaMM KyjibTHBHpyeTCH πγτβΜ aapoOHoň φβρΜβΗΤβηΗΗ B χπηκΗΧ HHTaTejibHbix cpe-nax, KOTopue coflepacaT ycBoneMbie hctovhhkh yrnepona, a3OTa h MHHepajibHbút co-jieň, b ríiyCHHHbix η/ηπη ποβθρχηοοτημχ KyjibTypax npn TeMnepaType ot 20-30°C haHaneHHH pH - ot 4,0 po 6,2 b TeveHHe 7-35 ffHeň.
Bonee 95? oCpaayeMbix ajiKanoiwoB BbinejiHioTcn b nHTaTejibHyio cpeny, H3 κοτοροήohh nerKO HSonnpyioTCH. IIpnaHaHo Η3θ6ρβτβΗΗβΜ no peaynbTaTaM 3KcnepTH3bi, ocymecTBnéHHoň BenoMCTBOMno nenaM Η3θβρβτβΗΗή η πβτβπτοΒ TflP. 258001
Claims (2)
1. Způsob výroby ergotaminu, vyznačující ee tím, Se kmenOlavloepe purpurea /Pr./ Tul. IBP 74» IMET PA 135, Jeho mu-tanty a varianty ee kultivují aerobní fermentací v tekutémživném prostředí, které obsahuje zdroj uhlíku, dusíku a mi-narálníoh solí v povrchové a/nebo hlubinné kultuře při tep-lotě 20 až 30 °0 a pH 4,0 až 6,2 po dobu 7 až 3? dní a Vzniklý ergotamin/ergotaminin se izoluje ze živné půdy známýmzpůsobem·
2· Způsob podle bodu 1, vyznačující se tím, že se fermenta-oe provádí při teplotě 20 až 25 °C a pH 5,2 až 5,9· Uzgorodsky výrobne-polygrafický podnik, Proektnaja 4, Uzgorod »4880,Cena 2,40 Kcs
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD21723579A DD234172A3 (de) | 1979-07-16 | 1979-07-16 | Verfahren zur herstellung von ergotamin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS258001B1 true CS258001B1 (en) | 1988-07-15 |
Family
ID=5521316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS794080A CS258001B1 (en) | 1979-07-16 | 1980-11-20 | Method of ergotamine production |
Country Status (2)
| Country | Link |
|---|---|
| CS (1) | CS258001B1 (cs) |
| DD (1) | DD234172A3 (cs) |
-
1979
- 1979-07-16 DD DD21723579A patent/DD234172A3/de unknown
-
1980
- 1980-11-20 CS CS794080A patent/CS258001B1/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DD234172A3 (de) | 1986-03-26 |
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