DE69233348D1 - Verwendung von allosterischen hämoglobinmodifikatoren zur verringerung der sauerstoffaffinität im blut - Google Patents

Verwendung von allosterischen hämoglobinmodifikatoren zur verringerung der sauerstoffaffinität im blut

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Publication number
DE69233348D1
DE69233348D1 DE69233348T DE69233348T DE69233348D1 DE 69233348 D1 DE69233348 D1 DE 69233348D1 DE 69233348 T DE69233348 T DE 69233348T DE 69233348 T DE69233348 T DE 69233348T DE 69233348 D1 DE69233348 D1 DE 69233348D1
Authority
DE
Germany
Prior art keywords
blood
fffinity
modificators
reduce oxygen
hemoglobin
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 - Fee Related
Application number
DE69233348T
Other languages
English (en)
Other versions
DE69233348T2 (de
Inventor
Donald J Abraham
Mona Mahran
Ahmed Mehanna
Ramnarayan Randad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Virginia Commonwealth University
Virginia Commonwealth University Intellectual Property Foundation
Original Assignee
Virginia Commonwealth University
Virginia Commonwealth University Intellectual Property Foundation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US07/702,947 external-priority patent/US5122539A/en
Application filed by Virginia Commonwealth University, Virginia Commonwealth University Intellectual Property Foundation filed Critical Virginia Commonwealth University
Application granted granted Critical
Publication of DE69233348D1 publication Critical patent/DE69233348D1/de
Publication of DE69233348T2 publication Critical patent/DE69233348T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/325Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/01Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/29Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/64Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/67Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/68Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/73Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/32Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C235/38Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06Esters of carbamic acids
    • C07C271/40Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
    • C07C271/58Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00Systems containing two condensed rings
    • C07C2602/02Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/56Ring systems containing bridged rings
    • C07C2603/58Ring systems containing bridged rings containing three rings
    • C07C2603/70Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74Adamantanes

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Vascular Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
DE69233348T 1991-05-20 1992-05-19 Verwendung von allosterischen hämoglobinmodifikatoren zur verringerung der sauerstoffaffinität im blut Expired - Fee Related DE69233348T2 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US702947 1991-05-20
US07/702,947 US5122539A (en) 1990-02-12 1991-05-20 Allosteric hemoglobin modifiers useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood
US885721 1992-05-18
US07/885,721 US5248785A (en) 1990-02-12 1992-05-18 Using allosteric hemoglobin modifiers to decrease oxygen affinity in blood
PCT/US1992/004229 WO1992020335A1 (en) 1991-05-20 1992-05-19 Using allosteric hemoglobin modifiers to decrease oxygen affinity in blood

Publications (2)

Publication Number Publication Date
DE69233348D1 true DE69233348D1 (de) 2004-06-03
DE69233348T2 DE69233348T2 (de) 2005-05-12

Family

ID=27107045

Family Applications (2)

Application Number Title Priority Date Filing Date
DE69233348T Expired - Fee Related DE69233348T2 (de) 1991-05-20 1992-05-19 Verwendung von allosterischen hämoglobinmodifikatoren zur verringerung der sauerstoffaffinität im blut
DE69233320T Expired - Fee Related DE69233320D1 (de) 1991-05-20 1992-05-19 Verwendung allosterischer Hämoglobinmodifikatoren zur Verringerung der Sauerstoffaktivität im Blut

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE69233320T Expired - Fee Related DE69233320D1 (de) 1991-05-20 1992-05-19 Verwendung allosterischer Hämoglobinmodifikatoren zur Verringerung der Sauerstoffaktivität im Blut

Country Status (9)

Country Link
US (1) US5248785A (de)
EP (3) EP1236711B1 (de)
JP (1) JP3023423B2 (de)
AT (2) ATE260886T1 (de)
CA (1) CA2109575C (de)
DE (2) DE69233348T2 (de)
DK (2) DK1236711T3 (de)
ES (2) ES2223042T3 (de)
WO (1) WO1992020335A1 (de)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5705521A (en) * 1990-02-12 1998-01-06 The Center For Innovative Technology Use of allosteric hemoglobin modifiers in combination with radiation therapy to treat carcinogenic tumors
US5432191A (en) * 1990-02-12 1995-07-11 The Center For Innovative Technology Allosteric hemoglobin modifiers to decrease oxygen affinity in blood
US5677330A (en) * 1990-02-12 1997-10-14 The Center For Innovative Technology Medical uses of allosteric hemoglobin modifier compounds in patient care
US6458762B1 (en) 1994-03-28 2002-10-01 Baxter International, Inc. Therapeutic use of hemoglobin for preserving tissue viability and reducing restenosis
EP0767675A4 (de) * 1995-04-10 1998-08-05 Baxter Int Verwendung von vernetztem hämoglobin zur behandlung von subarachnoidalblutungen
US5733869A (en) * 1995-10-06 1998-03-31 Baxter International, Inc. Therapeutic administration of hemoglobin in cardiac arrest
AU2657597A (en) * 1996-03-21 1997-10-10 Dana-Farber Cancer Institute Use of allosteric haemoglobin modifier for treating solid tumors and inhibiting tumor metastases
JP2002501887A (ja) * 1998-01-28 2002-01-22 ワーナー−ランバート・カンパニー アルツハイマー病の治療方法
CA2384511A1 (en) * 1999-08-24 2001-03-01 Virginia Commonwealth University Substituted chiral allosteric hemoglobin modifiers
WO2001013933A2 (en) * 1999-08-25 2001-03-01 Gmp Companies, Inc. Agents for the enhanced oxygen delivery in mammals
DE10031741A1 (de) * 2000-06-29 2002-01-17 Sanguibio Tech Ag Einen Sauerstoffträger, ausgewählt aus Hämoglobin oder Hämoglobin- und Myoglobin-enthaltende Zubereitung als Externum zur natürlichen Regeneration der Haut bei Sauerstoff-Mangel
WO2002044127A1 (fr) * 2000-11-29 2002-06-06 Kyorin Pharmaceutical Co., Ltd. Dérivés d'acide carboxylique substitué
CA2439298A1 (en) * 2001-02-23 2002-09-06 Allos Therapeutics, Inc. Methods and reagents to acquire mri signals and images
US20030232887A1 (en) * 2002-04-10 2003-12-18 Johnson Douglas Giles Preparation and use of a stable formulation of allosteric effector compounds
US20050148991A1 (en) * 2002-05-21 2005-07-07 Johnson Douglas G. Device for using patient blood as diluent in administering pharmaceuticals
US20070259966A1 (en) * 2004-04-22 2007-11-08 Allos Therapeutics, Inc. Coadministration of Radiation, Efaproxiral Sodium, and Supplemental Oxygen for the Treatment of Cancer
CA2563752A1 (en) * 2004-04-22 2005-11-03 Allos Therapeutics, Inc. Compositions of allosteric hemoglobin modifiers and methods of making the same
US20050238727A1 (en) * 2004-04-22 2005-10-27 Cagnoni Pablo J Coadministration of radiation, efaproxiral sodium, and supplemental oxygen for the treatment of cancer
AU2005259579A1 (en) * 2004-07-01 2006-01-12 F. Hoffmann-La Roche Ag Phenyl derivatives comprising an acetylene group
WO2007123126A1 (ja) * 2006-04-17 2007-11-01 Juridical Foundation Osaka Industrial Promotion Organization 慢性心不全における運動耐容能低下の改善剤
BRPI0705396B1 (pt) * 2007-12-12 2021-10-05 Universidade Estadual De Campinas - Unicamp Compostos derivados ftalimídicos
WO2015100235A1 (en) 2013-12-27 2015-07-02 Virginia Commonwealth University Allosteric hemoglobin modifiers with nitric oxide releasing moiety

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2149070C3 (de) * 1971-10-01 1978-03-23 Boehringer Mannheim Gmbh, 6800 Mannheim Phenoxyalkylcarbonsäurederivate und deren Salze, Verfahren zu deren Herstellung und Arzneimittel
DE2432560A1 (de) * 1974-07-06 1976-01-22 Boehringer Mannheim Gmbh Neue phenoxyalkylcarbonsaeurederivate und verfahren zur herstellung derselben
DE2541342A1 (de) * 1975-09-17 1977-03-31 Boehringer Mannheim Gmbh Neue phenoxyalkylcarbonsaeuren und verfahren zur herstellung derselben
DE2546996C2 (de) * 1975-10-21 1984-07-05 Boehringer Mannheim Gmbh, 6800 Mannheim Phenoxyalkylcarbonsäure-Derivate, Verfahren zur Herstellung derselben sowie Arzneimittel, die diese Verbindungen als Wirkstoff enthalten
US4704402A (en) * 1982-06-12 1987-11-03 University Of Pittsburgh Method of treating sickle cell anemia
US4887995A (en) * 1985-01-22 1989-12-19 University Of Pittsburgh Method of treating sickle cell anemia
US4751244A (en) * 1986-04-04 1988-06-14 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4731473A (en) * 1986-04-04 1988-03-15 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4699926A (en) * 1986-04-04 1987-10-13 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4731381A (en) * 1986-04-04 1988-03-15 Merck & Co., Inc. Method of treating a person for sickle cell anemia
US5049695A (en) * 1990-02-12 1991-09-17 Center For Innovative Technology Allosteric hemoglobin modifiers
US5122539A (en) * 1990-02-12 1992-06-16 Center For Innovative Technology Allosteric hemoglobin modifiers useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood

Also Published As

Publication number Publication date
US5248785A (en) 1993-09-28
EP0585366A1 (de) 1994-03-09
ES2220857T3 (es) 2004-12-16
ATE260886T1 (de) 2004-03-15
DE69233348T2 (de) 2005-05-12
EP1468680A2 (de) 2004-10-20
ATE265208T1 (de) 2004-05-15
ES2223042T3 (es) 2005-02-16
EP0585366B1 (de) 2004-04-28
DE69233320D1 (de) 2004-04-08
WO1992020335A1 (en) 1992-11-26
CA2109575C (en) 2000-02-01
EP1236711A3 (de) 2002-09-18
EP1236711B1 (de) 2004-03-03
DK1236711T3 (da) 2004-08-16
JP3023423B2 (ja) 2000-03-21
EP1236711A2 (de) 2002-09-04
EP1468680A3 (de) 2005-04-13
DK0585366T3 (da) 2004-08-09
CA2109575A1 (en) 1992-11-26
EP0585366A4 (de) 1994-03-17
JPH07508973A (ja) 1995-10-05

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