CA1291054C - Antitumor antibiotics (ll-e33288 complex) - Google Patents
Antitumor antibiotics (ll-e33288 complex)Info
- Publication number
- CA1291054C CA1291054C CA000495303A CA495303A CA1291054C CA 1291054 C CA1291054 C CA 1291054C CA 000495303 A CA000495303 A CA 000495303A CA 495303 A CA495303 A CA 495303A CA 1291054 C CA1291054 C CA 1291054C
- Authority
- CA
- Canada
- Prior art keywords
- ethyl acetate
- potassium dihydrogen
- dihydrogen phosphate
- aqueous potassium
- alpha
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 33
- 229940088710 antibiotic agent Drugs 0.000 title claims abstract description 27
- 230000000259 anti-tumor effect Effects 0.000 title abstract description 10
- 241000187722 Micromonospora echinospora Species 0.000 claims abstract description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 246
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 111
- 150000001875 compounds Chemical class 0.000 claims description 55
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 49
- 239000002609 medium Substances 0.000 claims description 47
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 42
- 229920006395 saturated elastomer Polymers 0.000 claims description 38
- 238000000855 fermentation Methods 0.000 claims description 37
- 230000004151 fermentation Effects 0.000 claims description 37
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 37
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 36
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 36
- 238000001228 spectrum Methods 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 24
- 238000000862 absorption spectrum Methods 0.000 claims description 23
- 239000000741 silica gel Substances 0.000 claims description 21
- 229910002027 silica gel Inorganic materials 0.000 claims description 21
- 229910052740 iodine Inorganic materials 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 230000003115 biocidal effect Effects 0.000 claims description 15
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 14
- 239000011630 iodine Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 230000012010 growth Effects 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 244000005700 microbiome Species 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 238000000921 elemental analysis Methods 0.000 claims description 4
- 238000003306 harvesting Methods 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 8
- 238000010564 aerobic fermentation Methods 0.000 claims 3
- 239000012736 aqueous medium Substances 0.000 claims 3
- HXCHCVDVKSCDHU-PJKCJEBCSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-(ethylamino)-4-methoxyoxan-2-yl]oxy-4-hydroxy-6-[[(2s,5z,9r,13e)-9-hydroxy-12-(methoxycarbonylamino)-13-[2-(methyltrisulfanyl)ethylidene]-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-2-m Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-PJKCJEBCSA-N 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 239000002246 antineoplastic agent Substances 0.000 abstract description 8
- 241000187708 Micromonospora Species 0.000 abstract description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 101
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 229940093499 ethyl acetate Drugs 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- 239000000306 component Substances 0.000 description 33
- 238000012360 testing method Methods 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000004809 thin layer chromatography Methods 0.000 description 20
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000002054 inoculum Substances 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 239000013641 positive control Substances 0.000 description 11
- 101150041968 CDC13 gene Proteins 0.000 description 10
- 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 10
- 239000001888 Peptone Substances 0.000 description 10
- 108010080698 Peptones Proteins 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 235000019319 peptone Nutrition 0.000 description 10
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 9
- 229960004316 cisplatin Drugs 0.000 description 9
- 150000002500 ions Chemical class 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 8
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 8
- 235000010216 calcium carbonate Nutrition 0.000 description 8
- 239000008121 dextrose Substances 0.000 description 8
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- 238000000926 separation method Methods 0.000 description 8
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- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 7
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- 229920001817 Agar Polymers 0.000 description 5
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 230000000684 melanotic effect Effects 0.000 description 5
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 5
- 230000000171 quenching effect Effects 0.000 description 5
- GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 229920005654 Sephadex Polymers 0.000 description 4
- 239000012507 Sephadex™ Substances 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 229940009456 adriamycin Drugs 0.000 description 4
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- 239000003480 eluent Substances 0.000 description 4
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- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 4
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- GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
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- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
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- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
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- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/29—Micromonospora
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Compounds Of Unknown Constitution (AREA)
- Hydrogenated Pyridines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67203184A | 1984-11-16 | 1984-11-16 | |
| US672,031 | 1984-11-16 | ||
| US78706685A | 1985-10-17 | 1985-10-17 | |
| US787,066 | 1985-10-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1291054C true CA1291054C (en) | 1991-10-22 |
Family
ID=27100668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000495303A Expired - Lifetime CA1291054C (en) | 1984-11-16 | 1985-11-14 | Antitumor antibiotics (ll-e33288 complex) |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0182152B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JPH0774228B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR890001289B1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE180513T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU589918B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA1291054C (cg-RX-API-DMAC7.html) |
| DE (1) | DE3588213T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK168388B1 (cg-RX-API-DMAC7.html) |
| EG (1) | EG17709A (cg-RX-API-DMAC7.html) |
| ES (1) | ES8703160A1 (cg-RX-API-DMAC7.html) |
| FI (1) | FI86892C (cg-RX-API-DMAC7.html) |
| GR (1) | GR852725B (cg-RX-API-DMAC7.html) |
| HU (1) | HU195855B (cg-RX-API-DMAC7.html) |
| IL (7) | IL76878A (cg-RX-API-DMAC7.html) |
| LV (1) | LV12523B (cg-RX-API-DMAC7.html) |
| MX (1) | MX9203146A (cg-RX-API-DMAC7.html) |
| NO (1) | NO163574C (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ214114A (cg-RX-API-DMAC7.html) |
| PT (1) | PT81493B (cg-RX-API-DMAC7.html) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3440423A1 (de) * | 1984-11-06 | 1986-05-07 | Dr. Karl Thomae Gmbh, 7950 Biberach | Antibiotisches polypeptid, verfahren zu seiner herstellung, dieses polypeptid erzeugender stamm von staphylococcus epidermidis, dieses polypeptid enthaltende zubereitungsformen und seine verwendung zur bekaempfung infektioeser erkrankungen |
| US5024948A (en) * | 1985-10-17 | 1991-06-18 | American Cyanamid Company | Genetic system for micromonospora |
| SG52432A1 (en) * | 1987-01-30 | 1998-09-28 | American Cyanamid Co | Antitumor antibiotics (pseudoaglycone and dihydro derivatives of ll-33228 complex) |
| US4980297A (en) * | 1987-02-27 | 1990-12-25 | Becton, Dickinson And Company | Device for the membrane separation of the components of a liquid sample |
| ATE112172T1 (de) * | 1987-10-30 | 1994-10-15 | American Cyanamid Co | Targetformer von antitumor-methyltrithioagenzien. |
| EP0330874A3 (en) * | 1988-02-29 | 1989-10-18 | American Cyanamid Company | Antibacterial and antitumor agents LL-E33288 epsilon-I and LL-E33288-epsilonBr, with processes and intermediates for producing said agents |
| US4978748A (en) * | 1988-02-29 | 1990-12-18 | American Cyanamid Company | Intermediate and process for producing the antibacterial and antitumor agents LL-E33288ε-I and LL-E33288Epsilon-Br |
| US4996305A (en) * | 1988-02-29 | 1991-02-26 | American Cyanamid Company | Process for producing the antibiotic and antitumor agents LL-E33288.epsilon.ε-Br |
| US4977143A (en) * | 1988-02-29 | 1990-12-11 | American Cyanamid Company | Antibacterial and antitumor agents LL-E33288EPSILON-I and LL-E33288EPSILON-BR |
| EP0342341A3 (en) * | 1988-05-17 | 1991-07-24 | American Cyanamid Company | Process for producing antitumor antibiotic ll-e33288gamma2 |
| IL94540A0 (en) * | 1989-06-29 | 1991-03-10 | American Cyanamid Co | Antibiotic ll-e19085 |
| CN109553646A (zh) * | 2019-01-21 | 2019-04-02 | 浙江海正药业股份有限公司 | 一种纯化卡里奇霉素的制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU515150B2 (en) * | 1975-02-18 | 1981-03-19 | Sterling Drug Inc. | Preparation of aminocyclitol antibiotics |
| GR77567B (cg-RX-API-DMAC7.html) * | 1982-08-26 | 1984-09-24 | Lepetit Spa | |
| US4843008A (en) * | 1984-12-24 | 1989-06-27 | Yamanouchi Pharmaceutical Co., Ltd. | Novel microorganisms and a novel process for producing antibiotics |
-
1985
- 1985-10-29 DE DE3588213T patent/DE3588213T2/de not_active Expired - Lifetime
- 1985-10-29 AT AT85113751T patent/ATE180513T1/de not_active IP Right Cessation
- 1985-10-29 IL IL76878A patent/IL76878A/xx not_active IP Right Cessation
- 1985-10-29 EP EP85113751A patent/EP0182152B1/en not_active Expired - Lifetime
- 1985-11-08 NZ NZ214114A patent/NZ214114A/xx unknown
- 1985-11-11 GR GR852725A patent/GR852725B/el unknown
- 1985-11-14 PT PT81493A patent/PT81493B/pt unknown
- 1985-11-14 CA CA000495303A patent/CA1291054C/en not_active Expired - Lifetime
- 1985-11-15 ES ES548953A patent/ES8703160A1/es not_active Expired
- 1985-11-15 AU AU49957/85A patent/AU589918B2/en not_active Expired
- 1985-11-15 DK DK529685A patent/DK168388B1/da not_active IP Right Cessation
- 1985-11-15 HU HU854365A patent/HU195855B/hu unknown
- 1985-11-15 FI FI854510A patent/FI86892C/fi not_active IP Right Cessation
- 1985-11-15 JP JP60255157A patent/JPH0774228B2/ja not_active Expired - Lifetime
- 1985-11-15 KR KR1019850008548A patent/KR890001289B1/ko not_active Expired
- 1985-11-15 NO NO854578A patent/NO163574C/no not_active IP Right Cessation
- 1985-11-17 EG EG731/85A patent/EG17709A/xx active
-
1990
- 1990-02-16 IL IL93421A patent/IL93421A0/xx unknown
- 1990-02-16 IL IL93418A patent/IL93418A0/xx unknown
- 1990-02-16 IL IL93416A patent/IL93416A0/xx unknown
- 1990-02-16 IL IL93420A patent/IL93420A0/xx unknown
- 1990-02-16 IL IL93419A patent/IL93419A0/xx unknown
- 1990-02-16 IL IL93417A patent/IL93417A0/xx unknown
-
1992
- 1992-06-23 MX MX9203146A patent/MX9203146A/es unknown
-
2000
- 2000-05-19 LV LVP-00-64A patent/LV12523B/lv unknown
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| MKEX | Expiry |