WO1991010645A3 - Agents de chelation - Google Patents

Agents de chelation

Info

Publication number
WO1991010645A3
WO1991010645A3 PCT/EP1991/000126 EP9100126W WO9110645A3 WO 1991010645 A3 WO1991010645 A3 WO 1991010645A3 EP 9100126 W EP9100126 W EP 9100126W WO 9110645 A3 WO9110645 A3 WO 9110645A3
Authority
WO
WIPO (PCT)
Prior art keywords
chelants
radiotherapeutic
preparation
chelating agents
agents useful
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.)
Ceased
Application number
PCT/EP1991/000126
Other languages
English (en)
Other versions
WO1991010645A2 (fr
Inventor
Joan F Carvalho
Shaun P Crofts
Scott M Rocklage
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.)
Amersham Health Salutar Inc
Original Assignee
Salutar Inc
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
Application filed by Salutar Inc filed Critical Salutar Inc
Priority to CA002074171A priority Critical patent/CA2074171A1/fr
Priority to FI923286A priority patent/FI923286L/fi
Priority to JP91502458A priority patent/JPH05506426A/ja
Publication of WO1991010645A2 publication Critical patent/WO1991010645A2/fr
Publication of WO1991010645A3 publication Critical patent/WO1991010645A3/fr
Priority to NO92922849A priority patent/NO922849L/no
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasonic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasonic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/228—Host-guest complexes, clathrates, chelates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
    • A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Nanotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Optics & Photonics (AREA)
  • Medical Informatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Acoustics & Sound (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention se rapporte à de nouveaux agents de chélation utilisables dans la préparation d'agents de contraste pour des techniques de formation d'images diagnostiques ou dans la préparation de compositions radiothérapeutiques ou de détoxification.
PCT/EP1991/000126 1990-01-19 1991-01-18 Agents de chelation Ceased WO1991010645A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002074171A CA2074171A1 (fr) 1990-01-19 1991-01-18 Agents chelateurs
FI923286A FI923286L (fi) 1990-01-19 1991-01-18 Kelateringsaemnen.
JP91502458A JPH05506426A (ja) 1990-01-19 1991-01-18 キレート化剤
NO92922849A NO922849L (no) 1990-01-19 1992-07-17 Chelateringsmidler

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB909001245A GB9001245D0 (en) 1990-01-19 1990-01-19 Compounds
GB9001245.1 1990-01-19

Publications (2)

Publication Number Publication Date
WO1991010645A2 WO1991010645A2 (fr) 1991-07-25
WO1991010645A3 true WO1991010645A3 (fr) 1991-12-26

Family

ID=10669570

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1991/000126 Ceased WO1991010645A2 (fr) 1990-01-19 1991-01-18 Agents de chelation

Country Status (10)

Country Link
EP (1) EP0527131A1 (fr)
JP (1) JPH05506426A (fr)
AU (1) AU7060291A (fr)
CA (1) CA2074171A1 (fr)
FI (1) FI923286L (fr)
GB (1) GB9001245D0 (fr)
HU (1) HUT61306A (fr)
IE (1) IE910189A1 (fr)
NO (1) NO922849L (fr)
WO (1) WO1991010645A2 (fr)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5334371A (en) * 1988-07-20 1994-08-02 Schering Aktiengesellschaft Marcocyclic polyaza bicyclo compounds containing 5 or 6 membered rings, and method for MRI
FR2644785B1 (fr) * 1989-03-24 1991-07-05 Guerbet Sa Nouveaux ligands macrocycliques azotes, procede de preparation, complexes metalliques formes par ces ligands et composition de diagnostic les contenant
US5367080A (en) * 1990-11-08 1994-11-22 Sterling Winthrop Inc. Complexing agents and targeting radioactive immunoreagents useful in therapeutic and diagnostic imaging compositions and methods
CA2072934C (fr) * 1991-07-19 2007-08-28 Karl William Aston Complexes de manganese et de ligands macrocycliques contenant de l'azote, efficaces comme catalyseurs de la dismutation de superoxydes
SG46598A1 (en) * 1991-12-10 1998-02-20 Dow Chemical Co Bicycloazamacroyclophosphonic acid conjugates contrast agents and preparation
US5739294A (en) * 1991-12-10 1998-04-14 The Dow Chemical Company Bicyclopol yazamacrocyclophosphonic acid complexes for use as contrast agents
MX9207164A (es) * 1991-12-10 1993-07-01 Dow Chemical Co Complejos de acido biciclopoliazamacrociclocarboxilico, sus conjugados, procedimientos para su preparacion y su uso como agentes de contraste.
US5428139A (en) * 1991-12-10 1995-06-27 The Dow Chemical Company Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals
AU3324193A (en) * 1991-12-10 1993-07-19 Dow Chemical Company, The Oral compositions for inhibiting plaque and calculus formation
BR9207126A (pt) * 1992-05-07 1995-08-29 Sterling Winthrop Inc Imunorreagente radioativo de marcação,composição formadora de imagem,composição terapêutica,processo para a formação de imagem diagnóstica em um sítio em um paciente e para tratar sítios de doença em um paciente,e,composição de matéria
FI933506A7 (fi) * 1993-05-06 1994-11-07 Dow Global Technologies Inc Bisyklopolyatsamakrosyklokarboksyylihappokomplekseja, niiden konjugaat teja, menetelmä niiden valmistamiseksi ja käyttö varjoaineina
EP0696290A1 (fr) * 1993-05-06 1996-02-14 The Dow Chemical Company Acides bicyclopolyazamacrocyclophosphoniques, leurs complexes et conjugues, destines a etre utilises en tant qu'agents de contraste, et leurs procedes de preparation
WO1994026755A1 (fr) * 1993-05-06 1994-11-24 The Dow Chemical Company Complexes d'acides bicyclopolyazamacrocyclophosphoniques, conjugues de ces derniers, procede de preparation associe et d'utilisation en tant que produits radiopharmaceutiques
WO1994026315A1 (fr) * 1993-05-06 1994-11-24 The Dow Chemical Company Complexes et conjugues de complexes d'acides bicyclopolyazamacrocyclocarboxyliques, procedes de preparation de ces derniers et d'utilisation en tant que produits radiopharmaceutiques
US5476644A (en) * 1994-04-13 1995-12-19 Sterling Winthrop Inc. Cyclic triamine chelating agents
WO1996030377A1 (fr) 1995-03-27 1996-10-03 Isis Pharmaceuticals, Inc. Composes macrocycliques azotes
US6207826B1 (en) 1995-03-27 2001-03-27 Isis Pharmaceuticals, Inc. Macrocyclic compounds having nitrogen-containing linkages
US6525041B1 (en) 1995-06-06 2003-02-25 Pharmacia Corporation Manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide
AU6722496A (en) * 1995-08-17 1997-03-12 Monsanto Company Methods of diagnostic image analysis using metal complexes of nitrogen-containing macrocyclic ligands
EP0846003A1 (fr) 1995-08-17 1998-06-10 Monsanto Company Methodes d'analyse d'images diagnostiques utilisant des conjugues biologiques de complexes metalliques de ligands macrocycliques renfermant de l'azote
GB9702978D0 (en) * 1997-02-13 1997-04-02 Ciba Geigy Compounds
US6214817B1 (en) 1997-06-20 2001-04-10 Monsanto Company Substituted pyridino pentaazamacrocyle complexes having superoxide dismutase activity
US9855279B2 (en) 2006-10-12 2018-01-02 Galera Labs, Llc Methods of treating oral mucositis
US20090208421A1 (en) * 2008-02-19 2009-08-20 Dominique Meyer Process for preparing a pharmaceutical formulation of contrast agents
JP6267638B2 (ja) 2011-09-26 2018-01-24 ガレラ・ラブス・リミテッド・ライアビリティ・カンパニーＧａｌｅｒａ Ｌａｂｓ， Ｌｌｃ 疾患の治療方法
JP6608805B2 (ja) * 2013-04-26 2019-11-20 ゲルベ 造影製剤および関連する調製方法
IL297735B2 (en) 2015-08-11 2024-08-01 Galera Labs Llc Macrocyclic ring pentase complexes with oral bioavailability
KR20230075528A (ko) 2016-05-03 2023-05-31 갈레라 랩스, 엘엘씨 암 치료를 위한 조합 요법
GB201610738D0 (en) 2016-06-20 2016-08-03 Ge Healthcare As Chelate compounds
EP3506907B1 (fr) 2016-09-01 2023-06-07 Galera Labs, LLC Polythérapie anticancéreuse avec un complexe d'un cycle macrocyclique pentaaza et un composé ascorbate
IL295620B2 (en) 2017-04-13 2024-01-01 Galera Labs Llc Combination cancer immunotherapy with pentaaza macrocyclic ring complex

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2751390A (en) * 1950-09-02 1956-06-19 Dow Chemical Co Di-pyridyl aliphatic alkylene polyamine poly acids
WO1986006605A1 (fr) * 1985-05-08 1986-11-20 The General Hospital Corporation Agents de contraste hepatobiliaire pour resonance magnetique nucleaure
WO1989011868A1 (fr) * 1988-05-31 1989-12-14 Coulter Electronics, Inc. Composes macrocycliques d'yttrium, de lanthanides et d'actinides a fonctions peripheriques de liaison
EP0352218A2 (fr) * 1988-07-20 1990-01-24 Schering Aktiengesellschaft Composés polyaza macrocycliques, leur procédé de préparation et compositions pharmaceutiques les contenant
WO1990011282A1 (fr) * 1989-03-24 1990-10-04 Guerbet S.A. Ligands macrocycliques azotes et leurs complexes metalliques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2751390A (en) * 1950-09-02 1956-06-19 Dow Chemical Co Di-pyridyl aliphatic alkylene polyamine poly acids
WO1986006605A1 (fr) * 1985-05-08 1986-11-20 The General Hospital Corporation Agents de contraste hepatobiliaire pour resonance magnetique nucleaure
WO1989011868A1 (fr) * 1988-05-31 1989-12-14 Coulter Electronics, Inc. Composes macrocycliques d'yttrium, de lanthanides et d'actinides a fonctions peripheriques de liaison
EP0352218A2 (fr) * 1988-07-20 1990-01-24 Schering Aktiengesellschaft Composés polyaza macrocycliques, leur procédé de préparation et compositions pharmaceutiques les contenant
WO1990011282A1 (fr) * 1989-03-24 1990-10-04 Guerbet S.A. Ligands macrocycliques azotes et leurs complexes metalliques

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, vol. 113, no. 7, 13 August 1990, (Columbus, Ohio, US), K.I. Dhont et al: "Metal ion template synthesis of the macrocyclic multidentate polyamine ligand: 3,6,14,17,23,24-hexa azatricyclo(17.3.1.1 8,12)tetraeicosa-1(22),8(9), 10,12,19,20-hexaene", abstract 59129d & Bull. Soc. Chim. Belg. 1989, 98(8),575-6, see reg no 127503-08-6 *
Helvetica Chimica Acta, vol. 72, August 1989, M.W. Hosseini et al: "Synthesis of polyaza macrocyclic ligands incorporating pyridine units", pages 1066-1077, see especially compounds 4, 5, 21 and 22 *
Inorg. Chem., vol. 25, no. 4, 1986, E.K. Barefield et al: "Electrochemical and Structural Studies of Nickel(II) Complexes of N-Alkylated Cyclam Ligands: X-ray Structures of trans-/Ni(C14H32N4)(OH2)2/ Cl2.2H2O and /Ni(C14H32N4)/(O3SCF3)2", pages 552-558, see compound D *
J. Am. Chem. Soc., vol. 110, no. 9, 1988, R.D. Hancock et al: "More rigid Macrocyclic Ligands That Show Metal Ion Size-Based Selectivity. A Crystallographic, Molecular Mechanics, and Formation Constant Study of the Complexes of BridgedCyclen", pages 2788-2794, see tables I and VI *
J. Am. Chem. Soc., vol. 111, September 1989, P.H. Smith et al: "Solution and solid-state characterization of Europium and Gadolinium schiff base complexes and assessment of their potential as contrast agents in magnetic resonance imaging", pages 7437-7443, see the whole article *
J. Am. Chem. Soc., vol.87, 1965, R.G. Lacoste et al: "New Multidentate Ligands. II. Amino Acids Containing alfa-Pyridyl Groups", pages 2385-2388, see the whole document *
J. Chem. Soc. Dalton Trans., December 1988, N.W. Alcock et al:"Synthesis and Co-ordination Chemistry of Two Penta-azamacrocycles containing a 1,4-Piperazine Backbone. Crystal Structure Determinations of 6,12-Dioxo-1,5,13,17,22-penta- -azatricyclo/15.2.2.1 7,11/docosa-7(22),8,10- -triene and 1,5,13,17,22-Penta-azatricyclo /15.2.2.1 7,11/docosa-7(22),8,10-trienenickel(II) Perchlorate", pages 2959-2963, see compound L2 and tables 1 and 2 *
J. Chem. Soc., Chem. Commun., 1982, A. Ramasubbu et al: "Structurally Reinforced Cyclen: A Rigidly trans-Co-ordinating Twelve-membered Macrocycle", pages 277-278, see compound 2 *
J. Chem. Soc., Chem. Commun., 1985, N.W. Alcock et al: "Co-ordination to Copper(II) by OnlyThree Nitrogen Atoms of a Tetra-azamacro- cyclic Ligand functionalised with Two Pendant Acetate-arms. X-Ray Structure of /Cu(L1H2)Cl/Cl, where L1 is 3,11-Diacetato-7-methyl-3,7,11,17- -tetraazabicyclo/11.3.1/heptadeca-1(17),13,15- -triene", pages 1058-1059, see compound L1 *
J. Phys. Chem., vol. 91, no. 18, 1987, N. Sabbatini et al: "Radiative and Nonradiative Transitions in the Eu(III) Hexaaza Macrocyclic Complex /Eu(C22H26N6)(CH3COO)/(CH3COO)Cl.2H2O pages 4681-4685, see the whole document *
Tetrahedron, vol. 37, 1981, H. Stetter et al: "Darstellung und Komplexbildung von Polyazacyclo- alkan-N-Essigs{uren, pages 767-772, see especially compounds 19 and 31 *

Also Published As

Publication number Publication date
FI923286A7 (fi) 1992-07-17
EP0527131A1 (fr) 1993-02-17
FI923286A0 (fi) 1992-07-17
HUT61306A (en) 1992-12-28
FI923286L (fi) 1992-07-17
AU7060291A (en) 1991-08-05
NO922849D0 (no) 1992-07-17
WO1991010645A2 (fr) 1991-07-25
CA2074171A1 (fr) 1991-07-20
IE910189A1 (en) 1991-07-31
NO922849L (no) 1992-09-04
GB9001245D0 (en) 1990-03-21
HU9202347D0 (en) 1992-10-28
JPH05506426A (ja) 1993-09-22

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