DK147304B - Analogifremgangsmaade til fremstilling af (-) daunosaminyl-4-demethoxydaunomycinon som en blanding af (7s : 9r) og (7r : 9r) alfa-anomere - Google Patents
Analogifremgangsmaade til fremstilling af (-) daunosaminyl-4-demethoxydaunomycinon som en blanding af (7s : 9r) og (7r : 9r) alfa-anomere Download PDFInfo
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- DK147304B DK147304B DK256875AA DK256875A DK147304B DK 147304 B DK147304 B DK 147304B DK 256875A A DK256875A A DK 256875AA DK 256875 A DK256875 A DK 256875A DK 147304 B DK147304 B DK 147304B
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- daunosaminyl
- anomers
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- imi
- adriamycin
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- 229940009456 adriamycin Drugs 0.000 description 12
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- ZUFQFGSMHXKORU-UHFFFAOYSA-N 9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(O)=C1C(O)CC(C(=O)C)(O)CC1=C2O ZUFQFGSMHXKORU-UHFFFAOYSA-N 0.000 description 2
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- 230000003000 nontoxic effect Effects 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
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- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
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- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
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- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
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- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Description
147304
Opfindelsen angår en analogi'fremgangsmåde til fremstilling af (-) daunosaminyl-4-demethoxydaunomycinon som en blanding af (7S : 9S) og (7R : 9R) £?C-anomere (som er analoge til daunomycin, beskrevet i GB patentbeskrivelse nr.l 003 383), hvilke analoge har en modificeret ring D og den almene formel:
O °H
C0CH3
''OH
0 OH | Æ*
NHZ
2 147304
Fremgangsmåden ifølge opfindelsen, som er ejendommelig ved det i kravets kendetegnende del anførte, omfatter kondensation af 2,3,6-trideoxy-3-triflour-acetaraido-4-triflouracetoxy-<pd-L-lyxopyranosylchlorid med en anthracyclinon med den i kravets kendetegnende del angivne formel i et vandfrit opløsningsmiddel i nærværelse af mercurioxid og/eller bromid og molecularsigte for at give et beskyttet derivat, som ved behandling med methanol og derefter med base f.eks. natriumhydroxid omdannes til den ønskede forbindelse. Det racemi-ske 4-demethoxydaunomycinon giver de to hidtil ukendte forbindelser: (-) dauno-saminyl(-)4-demethoxy-daunomycinon (OC+βanomere) og (-) daunosaminyl (+)4-de-methoxy-daunomycinon (<X.+(b anomere), som kan adskilles ved de sædvanlige metoder.
Det må forstås, at hver forbindelse, som har anthracyclinonkonfiguration ( 7S : 9S ) eller ( 7R : 9R ), er en blanding af cC og^anomere.
Fremgangsmåden ifølge opfindelsen illustreres af følgende eksempel.
EKSEMPEL·.
(-)daunosaminyl(-) -M-demethoxydaunomycinon ( <& + β> anomere) og (-)dåunoss-amJnyl(+).-4-demethoxydaunomycinon ( oC + β anomere).
a) 1,2 g 4“demethoxydaunomycinon-7-methylether ( fremstillet efter C. M. Wong, Canadian Journal ©f Chemestry, 1971» 42» 2712 ) opløses* i 22 ml trifluor-eddikesyre og henstår natten over ved stuetemperatur. Opløsningen inddampes i vacuum. Eemanensen opløses i 50 ml acetone og der tilsættea; 10 ml 5 % vandigt natriumbicarbonat. Efter 30 min. fjernes opløsningsmidlet ved ind-dampning i vacuum og remanensen opløses i chloroform og vaskes med vand. Fordampning af chlorofoimen efterlader en remanens, som kromatograferes på silicagel og giver 0,475 g (i)-4-demethoxydaunomycinon, smp. 152-155°C, enkelt plet ved tyndtlagskromatografi ( silicagel} chloroform : acetone ; 80 : 20; Bf = 0,44 ).
b) 0,3 g af denne forbindelse opløses i 75 ml vandfrit chloroform, og 0,6 g mercurioxid, 0,15 g mercuribromid og 5 δ 5 molecularsigte tilsættes under omrøring. Efter en time tilsættes 0,7 g 2,3,6-trides30xy-3-trifluor-acetamido-4-triflouracefcnxy- oc -L-lyxopyranosylchlorid og suspensionen omrøres ved stuetemperatur i 16 timer. Efter filtrering koncentreres opløsningen 3 147304 i vacuum og remanensen opløses i 200ml methanol og koges med tilbageløbskøling i 15 min. Efter fordampning af opløsningsmidlet kromatograferes remanensen på silicagel. Ved eluering med chloroform : benzen : methanol ; 100 : 20 i 3 , opnås 0,270 g af en blanding af (-)daunosaminyl(-)-4-demethoxy- daunomyoinon og (-)daunosaminyl(+)-4-demethoxydaunomycinon (06 -glycosyl anomere) som N-trifluoracetylderivater ( enkelt plet på silicagelplader; chloroform : acetone } 80 s 20 j Ef = 0,34), og 0,150 g af en blanding af (-)daunosaminyl(- )-4-demethoxydaunomycinon og (—)daunosaminyl(+).-4-demethoxy-daunomycinon ( /6 -glycosyl anomere) som N-trifluo racetyl derivater, c) 0,170 g N-t rif luo rac e tyl de r ivat e r af (—)daunosaminyl(—J-^-demethoxydaunomyci-non og (-)daunosaminyl(+)-4-demethoxydaunomycinon ( oc -glycosyl anomere) opløses i 0,1 N NaOH (15 ml) og henstår 30min. ved stuetemperatur, pH indstille® til 8,6 med HC1 og opløsningen ekstraheres gentagne gange med chloroform. Chloroformopløsningen koncentreres i vacuum og remanensen opløse® i methanol ( 5 ml) og gøres sur ( pH 4,5) med 0,1 N HC1 i methanol og ethyl-ether tilsættes for at bevirke udfældning af hydrochlorider af (-) daunosaminyl (-)-4-demethoxyaaunomycinon og (-)daunosaminyl(+)-4-demethoxydaunomycinon (ée-gly-cosid anomere) (enkelt plet på silicagelplader; dichlormethan: methanol: vand; 100 : 20 : 2 : Rf = 0,16).
I den farmakologiske vurdering som herefter beskrives anvendes for kortheds skyld laboratoriekoden "IMI 22" til at angive (-)dauhoaaminyl(-)-4-demethoxy-daunomycinon som en blanding af ( 7S :9S ) og ( 7H :9E ) oc -anomere.
Symbolerne "R" = Rectus og "S" = Sinister tages fra litteraturen ( i overensstemmelse med nomenclaturen i Cahn, Ingold, Prel og, Experientia, 1956.12-.
81).
4 147304
Virkning af IMI 22 på levedygtighed af EeLa celler.
In vi tro studier "blev udført på HeLa celler dyrket på Eagle medium tilsat 10 io kalvserum. Cellerne blev behandlet med forbindelser som skulle undersøgea 1 forskellige tidsrum. Levedygtigheden af cellerne blev bestemt og der blev udsået 2-300 celler pr. plade. Koloniantallene blev bestemt 6 dage senere. Resultaterne ( Tabel l) viser at IMI 22 er lige så aktiv som adriamycin efter 2 timers behandling, og efter 8 timers behandling er inhiberingen af cellelevedygtigheden højere med IMI 22 end med adriamycin og daunomyein.
Tabel 1 _IR 50 (/*g/ml)_ __2_t__8_b_
Daunomyein 0,095 0,023
Adriamycin ( 0,2 ) 0,039 IMI 22 ( 0,2 ) 0,002
In vitro forsøg er også blevet udført vedrørende dannelsen af foci af Moloney Sarcoma virus (MSV) til sammenligning med adriamycin på museembryo-fibroblast kulturer inficeret og ikke inficeret med MSV . Efter 3 dages behandling blev den procentuelle inhibering i sammenligning med kontrolforsøg vurderet efter celleproliferation i uinficerede kulturer ( oytotoxisk aktivitet) og efter MSV foci dannelse i inficerede kulturer (antiviral aktivitet). Resultaterne ( Tabel 2) viser for IMI 22 mindre antiviral aktivitet og samme cytotoxiske aktivitet som adriamycin.
Tabel 2
Dosis (k^/ml) $ Poci Celler
Adriamycin 0,0250 0 29 0,0125 0 30 0,006 26 53 IMI 22 0,6 0 0 0,1 0 4,6 0,0250 12 38 0,006 54 46 5 147304
In vivo studier af antitumor-aktiviteten af TMI 22 blev udført på nogle musetumorer både i fast og ascitisk form.
1. Ascitiske tumorer.
Aktivitetsforsøg blev udført på Swiss CD1 mus intraperitonealt inoculeret med 1 3E ΙΟ** ascitisk sarcoma 180 celler / dyr. Dyrene blev behandlet en gang intraperitonealt med forskellige koncentrationer af forbindelserne på den efter implantation af tumoren følgende dag. Resultaterne ( Tabel 3) angiver T/C % , d.v.s. middeloverlevelsestiden af behandlede mus / middeloverlevelsesn-tiden af kontroller i 100. Tallene i parentes (LTO) er antal langt idsoverlev. vende efter 60 dage. (l/ΐθ) angiver at af en gruppe på 10 forsøgsdyr forblev én i live efter 60 dage. MI 22 har en bemærkelsesværdig virkning på ascitisk tumorvækst : middeloverlevelsestiden af de behandlede dyr er betydeligt forøget. TMT 22 er aktiv i mindre doser end adriamycin.
Tabel 3
Dosis _jo T/C (LTO)__ “fifAfif/dag Porsøg 1 Forsøg 2__Forsøg 3 IMI 22 0,12 115 (θ/lO) 0,2 146 (0/10) 0 25 188 (1/10) 0,5 181 (0/10) 1 185 (0/10) 107 (o/lo) 223 (l/lO) 1,5 79 (0/10) 2 61 (1/10) 5 38 (0/10)___
Adriamycin 0,1 100 (O/lO) Ϊ*1 146 (1/9) I4I [ϊ/%θ] Ϊ69 (1/9) 2 ca 400 (5/I0) 5 311 (4/10) 225 (1/10) _ 10 _ 193 (0/10) _
Faste tumorer.
Forsøg med aktivitet på faste tumorer blev udført på Swiss CD1 mus subcutant podet med fragment eller neoplastisk væv og intravenøst behandlet i 5 dage begyndende dagen efter tumorimplantationen# På tiende dagen blev alle dyrene dræbt og deres tumorer fjernet og vejet. Resultaterne ( Tabel 4) viser at den højere ikke-toxiske dosis som blev prøvet ( 1 mg/kg) forårsager en inhibering 147304 6 af tumorraksten. på 50 f· Det terapeutiske index (T.l) "beregnet som maximum tolereret dosis (LD 10) / minimum effektiv dosis (Skipper and Schmidt, Cancer Chemotherapy Reports, I962, Γ7, 1 to 128). Minimum effektiv dosis er den dosis som reducerer vægten af tumorerne med 90 fo i sammenligning med kontrollerne. 90 fo reduktion svarer til T/C = 0,10 eller 10 fo . Det terapeutiske index (T,I.) er 3,7 for IMI 22 og 1,8 for adriamycin.
Tabel 4
Dosis tumor vægt fo T/C toxicitet __mg/kg_______
Kontroller___-__3,036_____ IMI 22 0,5 2,295 76 0/10 1 1,550 51 0/10 2 __0,485__16__3/10__
Adriamycin 2,5 1,465 48 O/lO
3.5 0,364_ 12_ 7/10__
Leukæmi.
Aktiviteten af IMI 22 blev prøvet på BDF 1 mus intraperitonealt inoculeret med 1 x 10^ L 1210 leukæmiceller / dyr. Dyrene blev behandlet én gang dagen efter tumorimplantationen. Resultaterne ( Tabel 5) viser at de ikké-toxiske doser som blev prøvet forøgede middeloverlevelsestiden af behandlede grupper anseligt. IMI 22 er aktiv i lavere doser end adriamycin.
Tabel 5 dosis middelover- fo T/C toxiaitet mg/kg levelsestid___
Kontroller__-__8___ IMI 22 0,75 12,5 156 0/10 1.5 13 162 1/10 ___3__7__87__7/10
Adriamycin 2,5 12,5 156 0/10 5 14 175 0/10 __[_10_ 16_ 200_4/10
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2608374 | 1974-06-12 | ||
| GB2608374A GB1467383A (en) | 1974-06-12 | 1974-06-12 | Daunomycin analogues |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK256875A DK256875A (da) | 1975-12-13 |
| DK147304B true DK147304B (da) | 1984-06-12 |
| DK147304C DK147304C (da) | 1984-12-17 |
Family
ID=10238087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK256875A DK147304C (da) | 1974-06-12 | 1975-06-09 | Analogifremgangsmaade til fremstilling af (-) daunosaminyl-4-demethoxydaunomycinon som en blanding af (7s : 9r) og (7r : 9r) alfa-anomere |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4046878A (da) |
| JP (1) | JPS5840557B2 (da) |
| AT (1) | AT337363B (da) |
| BE (1) | BE830090A (da) |
| BG (1) | BG61059B2 (da) |
| CH (1) | CH611317A5 (da) |
| DE (2) | DE19375027I2 (da) |
| DK (1) | DK147304C (da) |
| ES (1) | ES438431A1 (da) |
| FR (1) | FR2274629A1 (da) |
| GB (1) | GB1467383A (da) |
| HK (1) | HK982A (da) |
| MY (1) | MY103666A (da) |
| NL (1) | NL173272C (da) |
| SE (1) | SE423633B (da) |
| SU (1) | SU645588A3 (da) |
| ZA (1) | ZA753722B (da) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1506200A (en) * | 1975-04-30 | 1978-04-05 | Farmaceutici Italia | Glycosides |
| GB1509875A (en) * | 1976-06-14 | 1978-05-04 | Farmaceutici Italia | Optically active anthracyclinones and anthracycline glycosides |
| US4161480A (en) * | 1978-06-05 | 1979-07-17 | G. D. Searle & Co. | Intermediates for the synthesis of 4-demethoxydaunorubicin |
| US4201773A (en) * | 1978-07-26 | 1980-05-06 | The United States Of America As Represented By The Department Of Health, Education And Welfare | 7-O-(2,6-Dideoxy-α-L-lyxo-hexopyranosyl)-daunomycinone, desmethoxy daunomycinone, adriamycinone, and carminomycinone |
| IL55431A (en) * | 1978-08-24 | 1982-07-30 | Yeda Res & Dev | Anthracycline type antibiotics,their preparation and pharmaceutical compositions comprising them |
| NL8001417A (nl) * | 1979-03-17 | 1980-09-19 | Erba Farmitalia | Antitumorglycosiden. |
| JPS5673039A (en) * | 1979-08-20 | 1981-06-17 | Hoffmann La Roche | Naphthacene derivative |
| EP0024727B1 (en) * | 1979-09-01 | 1982-05-26 | FARMITALIA CARLO ERBA S.p.A. | Anthracycline glycosides, processes for their preparation and pharmaceutical composition containing them |
| DE3100968A1 (de) * | 1980-01-16 | 1982-01-14 | Farmitalia Carlo Erba S.p.A., 20159 Milano | Anthracyclinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US4348388A (en) * | 1980-04-02 | 1982-09-07 | G.D. Searle & Co. | 11-Amino-11-deoxydaunorubicin and analogs |
| ZA814722B (en) * | 1980-07-18 | 1982-07-28 | Hoffmann La Roche | Novel anthracycline glycosides |
| IT1210476B (it) * | 1981-05-28 | 1989-09-14 | Erba Farmitalia | Antracicline. |
| GB8317037D0 (en) * | 1983-06-23 | 1983-07-27 | Erba Farmitalia | 6-deoxyanthracyclines |
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| US4562177A (en) * | 1982-08-17 | 1985-12-31 | The Ohio State University Research Foundation | 3'-Amino-2' halo-anthracycline antibiotics |
| US4564674A (en) * | 1983-10-31 | 1986-01-14 | Sagami Chemical Research Center | Process for an anthracycline derivative, and an anthracyclinone derivative useful for the process |
| US4496485A (en) * | 1983-11-25 | 1985-01-29 | G. D. Searle & Co. | Asymmetric 7-O-(substituted acetyl)-4-demethoxydaunomycinones |
| US4537882A (en) * | 1984-05-10 | 1985-08-27 | Ohio State University | 4-Demethoxy-3'-desamino-2'-halo-anthracycline and pharmaceutical composition containing same |
| US4697005A (en) * | 1985-03-20 | 1987-09-29 | Ohio State University Research Foundation | 1-fluoro, 4-fluoro, and 1,4-difluoro anthracycline anticancer antibiotics |
| US5124317A (en) * | 1985-08-02 | 1992-06-23 | Farmitalia Carlo Erba S.P.A. | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
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| GB8803301D0 (en) * | 1988-02-12 | 1988-03-09 | Erba Carlo Spa | Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin |
| GB8808475D0 (en) * | 1988-04-11 | 1988-05-11 | Erba Carlo Spa | Process for preparing 4-demethoxydauno-mycinone |
| GB8818167D0 (en) * | 1988-07-29 | 1988-09-01 | Erba Carlo Spa | Novel 4-substituted anthracyclinones & process for their preparation |
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| WO2004033666A2 (en) * | 2002-10-11 | 2004-04-22 | Board Of Regents, The University Of Texas System | Method and compounds for inhibiting hec1 activity for the treatment of proliferative diseases |
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| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| CA2748057C (en) * | 2008-12-23 | 2018-07-03 | Pharmasset, Inc. | Nucleoside phosphoramidates |
| EP2376515A1 (en) * | 2008-12-23 | 2011-10-19 | Pharmasset, Inc. | Synthesis of purine nucleosides |
| US8551973B2 (en) * | 2008-12-23 | 2013-10-08 | Gilead Pharmasset Llc | Nucleoside analogs |
| KR101806323B1 (ko) | 2009-11-13 | 2017-12-07 | 다이이치 산쿄 유럽 게엠베하 | Ｈｅｒ-３ 관련 질병을 치료하거나 예방하기 위한 물질 및 방법 |
| CL2011000718A1 (es) | 2010-03-31 | 2012-04-09 | Gilead Pharmasset Llc | Proceso para la preparacion de compuestos fosforados enantiomericos. |
| JP2013540694A (ja) | 2010-08-06 | 2013-11-07 | ウー３・フアルマ・ゲー・エム・ベー・ハー | Ｈｅｒ３結合剤の前立腺治療における使用 |
| DE102011113652A1 (de) | 2011-09-19 | 2013-03-21 | Heraeus Precious Metals Gmbh & Co. Kg | Kristallisierung von Idarubicinhydrochlorid |
| TR201808733T4 (tr) | 2011-10-03 | 2018-07-23 | Mx Adjuvac Ab | Kanser tedavisini ve gıda ile ilgili bileşikleri içeren tıp alanlarında amfipatik veya hidrofobik moleküller için taşıyıcı olarak nano-parçacıklar, preparasyon için proses ve bunların kullanımı. |
| WO2014163558A1 (en) | 2013-04-01 | 2014-10-09 | Moreinx Ab | Nanoparticles, composed of sterol and saponin from quillaja saponaria molina process for preparation and use thereof as carrier for amphipatic of hydrphobic molecules in fields of medicine including cancer treatment and food related compounds |
| EP3669890A1 (en) | 2018-12-18 | 2020-06-24 | Croda International PLC | Filamentous nanoparticles having vaccine adjuvant effect |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3427300A (en) * | 1965-11-12 | 1969-02-11 | Merck & Co Inc | Anti-inflammatory steroid 2'-acetamido-2'-deoxy-glucoside compounds |
| US3803124A (en) * | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| US3686163A (en) * | 1968-05-14 | 1972-08-22 | Farmaceutici Italia | Dihydrodaunomycin antibiotic and derivatives thereof |
-
1974
- 1974-06-12 GB GB2608374A patent/GB1467383A/en not_active Expired
-
1975
- 1975-05-22 US US05/579,901 patent/US4046878A/en not_active Expired - Lifetime
- 1975-06-06 NL NLAANVRAGE7506745,A patent/NL173272C/xx not_active IP Right Cessation
- 1975-06-09 DE DE1993175027 patent/DE19375027I2/de active Active
- 1975-06-09 DK DK256875A patent/DK147304C/da not_active IP Right Cessation
- 1975-06-09 DE DE19752525633 patent/DE2525633A1/de active Granted
- 1975-06-09 SE SE7506589A patent/SE423633B/xx not_active IP Right Cessation
- 1975-06-09 AT AT437375A patent/AT337363B/de not_active IP Right Cessation
- 1975-06-09 FR FR7517881A patent/FR2274629A1/fr active Granted
- 1975-06-10 JP JP50069250A patent/JPS5840557B2/ja not_active Expired
- 1975-06-10 SU SU752141338A patent/SU645588A3/ru active
- 1975-06-10 ZA ZA00753722A patent/ZA753722B/xx unknown
- 1975-06-11 BE BE157205A patent/BE830090A/xx not_active IP Right Cessation
- 1975-06-11 CH CH756375A patent/CH611317A5/xx not_active IP Right Cessation
- 1975-06-11 ES ES438431A patent/ES438431A1/es not_active Expired
-
1982
- 1982-01-14 HK HK9/82A patent/HK982A/xx unknown
-
1988
- 1988-12-22 MY MYPI88001506A patent/MY103666A/en unknown
-
1993
- 1993-11-11 BG BG098211A patent/BG61059B2/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK147304C (da) | 1984-12-17 |
| AT337363B (de) | 1977-06-27 |
| FR2274629A1 (fr) | 1976-01-09 |
| DE2525633A1 (de) | 1976-01-02 |
| DE19375027I2 (de) | 2002-06-13 |
| JPS518260A (da) | 1976-01-23 |
| ATA437375A (de) | 1976-10-15 |
| NL173272B (nl) | 1983-08-01 |
| FR2274629B1 (da) | 1980-01-11 |
| US4046878A (en) | 1977-09-06 |
| DK256875A (da) | 1975-12-13 |
| SE423633B (sv) | 1982-05-17 |
| CH611317A5 (da) | 1979-05-31 |
| NL173272C (nl) | 1984-01-02 |
| HK982A (en) | 1982-01-22 |
| DE2525633C3 (da) | 1979-10-18 |
| BG61059B2 (bg) | 1996-09-30 |
| NL7506745A (nl) | 1975-12-16 |
| AU8197975A (en) | 1976-12-16 |
| DE2525633B2 (da) | 1979-03-01 |
| SE7506589L (sv) | 1975-12-15 |
| ES438431A1 (es) | 1977-02-01 |
| GB1467383A (en) | 1977-03-16 |
| SU645588A3 (ru) | 1979-01-30 |
| JPS5840557B2 (ja) | 1983-09-06 |
| BE830090A (fr) | 1975-12-11 |
| MY103666A (en) | 1993-08-28 |
| ZA753722B (en) | 1976-09-29 |
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Legal Events
| Date | Code | Title | Description |
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| PUP | Patent expired |