NO311357B1 - Sykliske nitroner og farmasöytiske preparater inneholdende disse - Google Patents
Sykliske nitroner og farmasöytiske preparater inneholdende disse Download PDFInfo
- Publication number
- NO311357B1 NO311357B1 NO19981054A NO981054A NO311357B1 NO 311357 B1 NO311357 B1 NO 311357B1 NO 19981054 A NO19981054 A NO 19981054A NO 981054 A NO981054 A NO 981054A NO 311357 B1 NO311357 B1 NO 311357B1
- Authority
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- Norway
- Prior art keywords
- nmr
- mmol
- cdcl
- dimethyl
- reaction
- Prior art date
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- 238000011002 quantification Methods 0.000 description 1
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- 238000011084 recovery Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
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- 238000002390 rotary evaporation Methods 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013319 spin trapping Methods 0.000 description 1
- BGPQEXQCXGECPX-UHFFFAOYSA-N spiro[1,2,4,5-tetrahydro-2-benzazepine-3,1'-cyclohexane] Chemical compound C1CCCCC21NCC1=CC=CC=C1CC2 BGPQEXQCXGECPX-UHFFFAOYSA-N 0.000 description 1
- QTCKGEQFWXCIJY-UHFFFAOYSA-N spiro[1,2,4,5-tetrahydro-2-benzazepine-3,4'-oxane] Chemical compound C1COCCC21NCC1=CC=CC=C1CC2 QTCKGEQFWXCIJY-UHFFFAOYSA-N 0.000 description 1
- GTQXBEVIGRNZSL-UHFFFAOYSA-N spiro[2,4-dihydro-1h-isoquinoline-3,4'-oxane] Chemical compound C1COCCC21NCC1=CC=CC=C1C2 GTQXBEVIGRNZSL-UHFFFAOYSA-N 0.000 description 1
- FIZGENHLZDGNFC-UHFFFAOYSA-N spiro[4,5-dihydro-2-benzazepine-3,1'-cyclohexane] Chemical compound C1CCCCC21N=CC1=CC=CC=C1CC2 FIZGENHLZDGNFC-UHFFFAOYSA-N 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/08—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with a hetero atom directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US355195P | 1995-09-11 | 1995-09-11 | |
PCT/US1996/013312 WO1997010218A1 (en) | 1995-09-11 | 1996-08-15 | Cyclic nitrones and pharmaceutical compositions containing them |
Publications (3)
Publication Number | Publication Date |
---|---|
NO981054D0 NO981054D0 (no) | 1998-03-10 |
NO981054L NO981054L (no) | 1998-03-10 |
NO311357B1 true NO311357B1 (no) | 2001-11-19 |
Family
ID=21706397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19981054A NO311357B1 (no) | 1995-09-11 | 1998-03-10 | Sykliske nitroner og farmasöytiske preparater inneholdende disse |
Country Status (21)
Country | Link |
---|---|
US (1) | US5962469A (zh) |
EP (1) | EP0863878B1 (zh) |
JP (1) | JPH11512427A (zh) |
KR (1) | KR100512675B1 (zh) |
CN (3) | CN1500787A (zh) |
AR (1) | AR004950A1 (zh) |
AT (2) | ATE293604T1 (zh) |
AU (1) | AU701989B2 (zh) |
CA (1) | CA2231812C (zh) |
DE (2) | DE69634647T2 (zh) |
DK (2) | DK1288203T3 (zh) |
ES (2) | ES2239194T3 (zh) |
HU (1) | HUP9803028A3 (zh) |
IL (1) | IL123345A (zh) |
MX (1) | MX9801892A (zh) |
NO (1) | NO311357B1 (zh) |
NZ (1) | NZ316288A (zh) |
PT (2) | PT1288203E (zh) |
TW (1) | TW337520B (zh) |
WO (1) | WO1997010218A1 (zh) |
ZA (1) | ZA967514B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1136212C (zh) * | 1998-01-16 | 2004-01-28 | 桑道药品有限公司 | 噻吩硝酮化合物 |
WO2000043397A1 (en) * | 1999-01-19 | 2000-07-27 | Neurosearch A/S | Fused heterocyclic compounds and their use in the treatment of neurodegenerative diseases |
CN100513395C (zh) * | 2006-04-17 | 2009-07-15 | 中国科学院化学研究所 | 一种制备多羟基环状硝酮的方法 |
CN101565453B (zh) * | 2008-04-22 | 2011-12-21 | 中国科学院化学研究所 | 具有捕获自由基功能的硝酮类化合物及其制备方法与应用 |
ES2395803B1 (es) * | 2011-08-01 | 2013-12-19 | Consejo Superior De Investigaciones Científicas (Csic) - 80% | Quinolilnitronas |
US8883857B2 (en) | 2012-12-07 | 2014-11-11 | Baylor College Of Medicine | Small molecule xanthine oxidase inhibitors and methods of use |
US10660851B2 (en) | 2015-01-02 | 2020-05-26 | Rxos Medical | Polyfunctional radical scavenger hydrogel formulation |
CN105985389B (zh) * | 2015-03-06 | 2019-03-19 | 北京大学 | 苯乙醇苷类似物及其合成方法和应用 |
JP7033081B2 (ja) * | 2016-02-08 | 2022-03-09 | ルナフォア・テクノロジーズ・エスアー | 試料サイクル多重化及びインサイツイメージングの方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
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US35112A (en) * | 1862-04-29 | Improvement in head-rests for car-seats | ||
US3044930A (en) * | 1960-12-08 | 1962-07-17 | Phillips Petroleum Co | N-oxides of heterocyclic nitrogen compounds as bird and rodent repellents |
US3796715A (en) * | 1967-08-30 | 1974-03-12 | Hoffmann La Roche | 8-alkoxy-3,4-dihydroisoquinolines |
US4123543A (en) * | 1971-09-16 | 1978-10-31 | Ab Kabi | Derivatives of substituted indoline lactans with effect on the central nervous system |
US4117144A (en) * | 1971-09-16 | 1978-09-26 | Ab Kabi | Derivatives of substituted isoindolines with effect on the central nervous system |
SE368009B (zh) * | 1971-09-16 | 1974-06-17 | Kabi Ab | |
JPS6363851A (ja) * | 1986-09-05 | 1988-03-22 | 孫七瓦工業株式会社 | 瓦の葺設方法 |
ES2044829T3 (es) * | 1989-10-17 | 1995-01-16 | Oklahoma Med Res Found | Metodo y composiciones para la inhibicion de alteraciones asociadas con las lesiones oxidativas de los tejidos. |
ATE209908T1 (de) * | 1991-06-18 | 2001-12-15 | Oklahoma Med Res Found | RADIKALFÄNGER (ßSPIN TRAPSß) ZUR BEHANDLUNG VON MIT OXIDATION VON LIPIDEN UND PROTEINEN VERBUNDENEN ERKRANKUNGEN |
US5292746A (en) * | 1991-09-12 | 1994-03-08 | Merrell Dow Pharmaceuticals Inc. | Cyclic nitrones, pharmaceutical compositions thereof and their use in treating shock |
NZ244268A (en) * | 1991-09-12 | 1994-09-27 | Merrell Pharma Inc | N-oxide quinoline derivatives and pharmaceutical compositions |
US5455272A (en) * | 1993-10-22 | 1995-10-03 | Oklahoma Medical Research Foundation | Spin trap nitronyl hindered phenols |
US5405967A (en) * | 1993-10-22 | 1995-04-11 | Oklahoma Medical Research Foundation | Spin-trap molecules 2-trifluoromethyl- of 5,5-dimethyl-1-dyrroline-N-oxide |
CA2152363A1 (en) * | 1993-10-25 | 1995-05-04 | Edward G. Janzen | Novel phosphorus-containing spin-trap compositions |
US5488145A (en) * | 1993-12-23 | 1996-01-30 | Oklahoma Medical Research Foundation | 2,4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceutical free radical traps |
US5472983A (en) * | 1994-04-14 | 1995-12-05 | Centaur Pharmaceuticals, Inc. | Benzamide-containing pharmaceutical compositions |
-
1996
- 1996-08-15 ES ES02024174T patent/ES2239194T3/es not_active Expired - Lifetime
- 1996-08-15 HU HU9803028A patent/HUP9803028A3/hu unknown
- 1996-08-15 MX MX9801892A patent/MX9801892A/es not_active IP Right Cessation
- 1996-08-15 AU AU68486/96A patent/AU701989B2/en not_active Ceased
- 1996-08-15 DK DK02024174T patent/DK1288203T3/da active
- 1996-08-15 PT PT02024174T patent/PT1288203E/pt unknown
- 1996-08-15 IL IL12334596A patent/IL123345A/xx not_active IP Right Cessation
- 1996-08-15 WO PCT/US1996/013312 patent/WO1997010218A1/en not_active Application Discontinuation
- 1996-08-15 CN CNA200310104608A patent/CN1500787A/zh not_active Withdrawn
- 1996-08-15 NZ NZ316288A patent/NZ316288A/xx unknown
- 1996-08-15 CN CNB96196877XA patent/CN1250528C/zh not_active Expired - Fee Related
- 1996-08-15 ES ES96928900T patent/ES2185797T3/es not_active Expired - Lifetime
- 1996-08-15 DE DE69634647T patent/DE69634647T2/de not_active Expired - Fee Related
- 1996-08-15 AT AT02024174T patent/ATE293604T1/de not_active IP Right Cessation
- 1996-08-15 EP EP96928900A patent/EP0863878B1/en not_active Expired - Lifetime
- 1996-08-15 CA CA002231812A patent/CA2231812C/en not_active Expired - Fee Related
- 1996-08-15 KR KR1019980701806A patent/KR100512675B1/ko not_active IP Right Cessation
- 1996-08-15 PT PT96928900T patent/PT863878E/pt unknown
- 1996-08-15 DK DK96928900T patent/DK0863878T3/da active
- 1996-08-15 JP JP9511955A patent/JPH11512427A/ja not_active Ceased
- 1996-08-15 AT AT96928900T patent/ATE230731T1/de not_active IP Right Cessation
- 1996-08-15 CN CNA200310104609A patent/CN1500779A/zh active Pending
- 1996-08-15 DE DE69625701T patent/DE69625701T2/de not_active Expired - Fee Related
- 1996-09-05 ZA ZA967514A patent/ZA967514B/xx unknown
- 1996-09-06 TW TW085110921A patent/TW337520B/zh active
- 1996-09-09 AR ARP960104278A patent/AR004950A1/es not_active Application Discontinuation
-
1997
- 1997-11-26 US US08/978,971 patent/US5962469A/en not_active Expired - Fee Related
-
1998
- 1998-03-10 NO NO19981054A patent/NO311357B1/no unknown
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