NO324560B1 - Kaskadepolymerkomplekser, fremgangsmate for fremstilling, samt farmasoytiske midler inneholdende disse - Google Patents
Kaskadepolymerkomplekser, fremgangsmate for fremstilling, samt farmasoytiske midler inneholdende disse Download PDFInfo
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- NO324560B1 NO324560B1 NO19980002A NO980002A NO324560B1 NO 324560 B1 NO324560 B1 NO 324560B1 NO 19980002 A NO19980002 A NO 19980002A NO 980002 A NO980002 A NO 980002A NO 324560 B1 NO324560 B1 NO 324560B1
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- 238000010790 dilution Methods 0.000 description 1
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- FHHGCKHKTAJLOM-UHFFFAOYSA-N hexaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCO FHHGCKHKTAJLOM-UHFFFAOYSA-N 0.000 description 1
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- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
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- DGAIEPBNLOQYER-UHFFFAOYSA-N iopromide Chemical compound COCC(=O)NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)N(C)CC(O)CO)=C1I DGAIEPBNLOQYER-UHFFFAOYSA-N 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
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- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
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- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- GDPGCHFFZZXKTQ-UHFFFAOYSA-N propyl 2-bromopropanoate Chemical compound CCCOC(=O)C(C)Br GDPGCHFFZZXKTQ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 229910001415 sodium ion Inorganic materials 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
-
- 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
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
-
- 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
- A61K49/12—Macromolecular compounds
- A61K49/124—Macromolecular compounds dendrimers, dendrons, hyperbranched compounds
-
- 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
- A61K51/06—Macromolecular compounds, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules
- A61K51/065—Macromolecular compounds, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules conjugates with carriers being macromolecules
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/76—Metal complexes of amino carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/54—Three nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/16—Dendrimers and dendritic polymers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Polyamides (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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DE19525924A DE19525924A1 (de) | 1995-07-04 | 1995-07-04 | Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
PCT/EP1996/002671 WO1997002051A2 (de) | 1995-07-04 | 1996-06-20 | Kaskaden-polymer-komplexe, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
Publications (3)
Publication Number | Publication Date |
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NO980002D0 NO980002D0 (no) | 1998-01-02 |
NO980002L NO980002L (no) | 1998-03-04 |
NO324560B1 true NO324560B1 (no) | 2007-11-19 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19980002A NO324560B1 (no) | 1995-07-04 | 1998-01-02 | Kaskadepolymerkomplekser, fremgangsmate for fremstilling, samt farmasoytiske midler inneholdende disse |
Country Status (27)
Country | Link |
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US (6) | US5820849A (cs) |
EP (1) | EP0836485B1 (cs) |
JP (1) | JP3723219B2 (cs) |
KR (1) | KR100428272B1 (cs) |
CN (2) | CN1079679C (cs) |
AT (1) | ATE220924T1 (cs) |
BG (1) | BG62600B1 (cs) |
BR (1) | BR9609478A (cs) |
CA (1) | CA2225959A1 (cs) |
CL (1) | CL2004001126A1 (cs) |
CZ (1) | CZ294951B6 (cs) |
DE (2) | DE19525924A1 (cs) |
DK (1) | DK0836485T3 (cs) |
ES (1) | ES2177792T3 (cs) |
HK (2) | HK1013915A1 (cs) |
IL (2) | IL122554A (cs) |
MX (1) | MX9800023A (cs) |
NO (1) | NO324560B1 (cs) |
NZ (1) | NZ312127A (cs) |
PL (1) | PL187712B1 (cs) |
PT (1) | PT836485E (cs) |
RU (1) | RU2166501C2 (cs) |
SK (1) | SK283838B6 (cs) |
TW (2) | TW579380B (cs) |
UA (1) | UA61890C2 (cs) |
WO (1) | WO1997002051A2 (cs) |
ZA (1) | ZA965686B (cs) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
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DE4425857A1 (de) * | 1994-07-07 | 1996-01-11 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zur ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
DE19525924A1 (de) * | 1995-07-04 | 1997-01-09 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
DE19652387A1 (de) * | 1996-12-04 | 1998-06-10 | Schering Ag | Macrocyclische Metallkomplexcarbonsäuren, ihre Verwendung sowie Verfahren zu ihrer Herstellung |
DE19728954C1 (de) * | 1997-06-30 | 1999-04-22 | Schering Ag | Saccharid-Konjugate, diese enthaltende pharmazeutische Mittel, Verfahren zu ihrer Herstellung und ihre Verwendung |
DE19729013A1 (de) * | 1997-07-03 | 1999-02-04 | Schering Ag | Oligomere, perfluoralkylhaltige Verbindungen, Verfahren zu deren Herstellung und ihre Verwendung in der NMR-Diagnostik |
US6019959A (en) * | 1997-07-31 | 2000-02-01 | Schering Aktiengesellschaft | Oligomeric compounds that contain perfluoroalkyl, process for their production, and their use in NMR diagnosis |
US7745142B2 (en) | 1997-09-15 | 2010-06-29 | Molecular Devices Corporation | Molecular modification assays |
US6297018B1 (en) | 1998-04-17 | 2001-10-02 | Ljl Biosystems, Inc. | Methods and apparatus for detecting nucleic acid polymorphisms |
DE19758105A1 (de) * | 1997-12-18 | 1999-06-24 | Schering Ag | Dendritische Polymer-Saccharid-Konjugate, diese enthaltende pharmazeutische Mittel, Verfahren zu ihrer Herstellung und ihre Verwendung |
US7405320B2 (en) * | 1998-06-22 | 2008-07-29 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
US6515113B2 (en) | 1999-02-18 | 2003-02-04 | The Regents Of The University Of California | Phthalamide lanthanide complexes for use as luminescent markers |
AU762754B2 (en) | 1999-02-18 | 2003-07-03 | Regents Of The University Of California, The | Salicylamide-lanthanide complexes for use as luminescent markers |
HUP0202635A3 (en) * | 1999-07-29 | 2006-03-28 | Epix Medical Inc Cambridge | Targeting multimeric imaging agents through multilocus binding |
US6549798B2 (en) * | 2001-02-07 | 2003-04-15 | Epix Medical, Inc. | Magnetic resonance angiography data |
AU2002350991A1 (en) * | 2001-06-25 | 2003-01-08 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | Macromolecular imaging agents for liver imaging |
DE10135356C1 (de) * | 2001-07-20 | 2003-04-17 | Schering Ag | Makrocyclische Metallkomplexe und deren Verwendung zur Herstellung von Konjugaten mit Biomolekülen |
TWI221406B (en) | 2001-07-30 | 2004-10-01 | Epix Medical Inc | Systems and methods for targeted magnetic resonance imaging of the vascular system |
GB0122049D0 (en) * | 2001-09-12 | 2001-10-31 | Nycomed Imaging As | Method |
US7648678B2 (en) | 2002-12-20 | 2010-01-19 | Dako Denmark A/S | Method and system for pretreatment of tissue slides |
AR047692A1 (es) * | 2003-07-10 | 2006-02-08 | Epix Medical Inc | Imagenes de blancos estacionarios |
EP1541568A1 (de) * | 2003-12-09 | 2005-06-15 | Deutsches Wollforschungsinstitut an der Rheinisch-Westfälischen Technischen Hochschule Aachen e.V. | Reaktive cyclische Carbonate und Harnstoffe zur Modifizierung von Biomolekülen, Polymeren und Oberflächen |
US7199268B2 (en) | 2003-12-16 | 2007-04-03 | Schering Aktiengesellschaft | Process for the production of dendritic trimesic acid triamides |
DE10361140B4 (de) * | 2003-12-16 | 2006-11-09 | Schering Ag | Verfahren zur Herstellung von dendritischen Trimesinsäuretriamiden, dabei verwendete Diethylentriaminderivate und Verwendung der Diethylentriaminderivate |
WO2006001835A2 (en) * | 2003-12-30 | 2006-01-05 | The Regents Of The University Of California | Aromatic triamide-lanthanide complexes |
US20050171424A1 (en) * | 2004-01-13 | 2005-08-04 | The Gov. Of The Usa As Rep. By The Secretary Of The Dept. Of Health And Human Services | Methods for imaging the lymphatic system using dendrimer-based contrast agents |
DE102004062258B3 (de) * | 2004-12-23 | 2006-01-05 | Schering Ag | Hydroxypyridinon-Derivate, deren Metallkomplexe und deren Verwendung zur Herstellung von Konjugaten mit Biomolekülen |
US20060204443A1 (en) * | 2005-03-11 | 2006-09-14 | The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health & Human Services | Methods for tumor treatment using dendrimer conjugates |
AU2007272604B2 (en) | 2006-07-10 | 2013-08-01 | The Regents Of The University Of California | Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides |
CA2660800C (en) * | 2006-08-15 | 2016-03-01 | The Regents Of The University Of California | Luminescent macrocyclic lanthanide complexes |
CA2660717A1 (en) * | 2006-08-17 | 2008-02-21 | Epix Pharmaceuticals, Inc. | Methods for lymph system imaging |
DE102007002726A1 (de) * | 2007-01-18 | 2008-07-31 | Bayer Schering Pharma Aktiengesellschaft | Neue Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
EP2114905B1 (en) * | 2007-01-25 | 2015-04-15 | Lumiphore, Inc. | Multi-color time resolved fluorophores based on macrocyclic lanthanide complexes |
DE102007058220A1 (de) | 2007-12-03 | 2009-06-04 | Bayer Schering Pharma Aktiengesellschaft | Dimere macrocyclisch substituierte Benzolderivate |
WO2009127715A1 (en) * | 2008-04-18 | 2009-10-22 | Ge Healthcare As | Compounds comprising paramagnetic chelates arranged around a central core and their use in magneto resonance imaging and spectroscopy |
US20100008864A1 (en) * | 2008-07-10 | 2010-01-14 | Andreas Meijer | Aromatic multimers |
US20100151591A1 (en) * | 2008-10-31 | 2010-06-17 | Butlin Nathaniel G | Rapid homogeneous diagnostic testing platform based on lanthanide fluorescent resonance energy transfer |
EP2816038B8 (en) | 2009-08-24 | 2019-12-25 | Lumiphore, Inc. | Hopo chelators |
WO2011079291A1 (en) * | 2009-12-24 | 2011-06-30 | Lumiphore, Inc. | Radiopharmaceutical complexes |
KR101334780B1 (ko) | 2010-08-13 | 2013-12-02 | 한국생명공학연구원 | 요오드를 함유한 방사형상의 고분자 화합물, 이의 제조방법 및 이를 포함하는 ct용 조영제 조성물 |
US9439984B2 (en) * | 2012-05-31 | 2016-09-13 | The Regents Of The University Of California | Macrocycles |
CA2891593C (en) | 2012-11-16 | 2021-09-14 | Lumiphore, Inc. | Di-macrocycles |
US11453652B2 (en) | 2013-03-15 | 2022-09-27 | Lumiphore, Inc. | Di-macrocycles |
EP3101012A1 (en) | 2015-06-04 | 2016-12-07 | Bayer Pharma Aktiengesellschaft | New gadolinium chelate compounds for use in magnetic resonance imaging |
CN110035996B (zh) | 2016-11-28 | 2022-08-09 | 拜耳医药股份公司 | 用于磁共振成像的新型高弛豫性钆螯合物 |
CN109503770B (zh) * | 2018-10-18 | 2021-03-09 | 合肥工业大学 | 一种具有高弛豫率的水溶性交联纳米聚合物及其合成方法和用途 |
KR20210095168A (ko) | 2018-11-23 | 2021-07-30 | 바이엘 악티엔게젤샤프트 | 조영 매체의 제형 및 그의 제조 방법 |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4587329A (en) * | 1984-08-17 | 1986-05-06 | The Dow Chemical Company | Dense star polymers having two dimensional molecular diameter |
US5527524A (en) * | 1986-08-18 | 1996-06-18 | The Dow Chemical Company | Dense star polymer conjugates |
US5135737A (en) * | 1986-11-10 | 1992-08-04 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Amplifier molecules for enhancement of diagnosis and therapy |
US4863717A (en) * | 1986-11-10 | 1989-09-05 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Methods for circumventing the problem of free radial reduction associated with the use of stable nitroxide free radicals as contrast agents for magnetic reasonance imaging |
US5364613A (en) * | 1989-04-07 | 1994-11-15 | Sieving Paul F | Polychelants containing macrocyclic chelant moieties |
GB8923843D0 (en) * | 1989-10-23 | 1989-12-13 | Salutar Inc | Compounds |
US5446145A (en) * | 1990-01-19 | 1995-08-29 | Nycomed Salutar, Inc. | Polychelant compounds |
DE3938992A1 (de) * | 1989-11-21 | 1991-05-23 | Schering Ag | Kaskadenpolymer-gebundene komplexbildner, deren komplexe und konjugate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
US5162109A (en) * | 1990-09-13 | 1992-11-10 | Mallinckrodt Medical, Inc. | Magnetic resonance imaging agents |
GB9024208D0 (en) * | 1990-11-07 | 1990-12-19 | Salutar Inc | Compounds |
US5385719A (en) * | 1991-09-24 | 1995-01-31 | Unger; Evan C. | Copolymers and their use as contrast agents in magnetic resonance imaging and in other applications |
US5405601A (en) * | 1993-07-02 | 1995-04-11 | Mallinckrodt Medical Inc. | Functionalized tripodal ligands for imaging applications |
US5534241A (en) * | 1993-07-23 | 1996-07-09 | Torchilin; Vladimir P. | Amphipathic polychelating compounds and methods of use |
US5449761A (en) * | 1993-09-28 | 1995-09-12 | Cytogen Corporation | Metal-binding targeted polypeptide constructs |
DE4344464A1 (de) * | 1993-12-22 | 1995-06-29 | Schering Ag | Kaskadenpolymere mit Iodaromaten |
DE4344460A1 (de) * | 1993-12-22 | 1995-06-29 | Schering Ag | Metallkomplexe von dendrimeren Makromolekülen, diese enthaltende diagnostische Mittel sowie Verfahren zur Herstellung der Komplexe und Mittel |
GB9404208D0 (en) * | 1994-03-04 | 1994-04-20 | Nycomed Salutar Inc | Chelants |
GB9407812D0 (en) * | 1994-04-20 | 1994-06-15 | Nycomed Salutar Inc | Compounds |
DE4425857A1 (de) * | 1994-07-07 | 1996-01-11 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zur ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
US5634613A (en) * | 1994-07-18 | 1997-06-03 | Mccarthy; Peter T. | Tip vortex generation technology for creating a lift enhancing and drag reducing upwash effect |
US5573750A (en) * | 1995-05-22 | 1996-11-12 | Nanosystems L.L.C. | Diagnostic imaging x-ray contrast agents |
DE19525924A1 (de) * | 1995-07-04 | 1997-01-09 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
US5874061A (en) * | 1995-12-22 | 1999-02-23 | Schering Aktiengesellschaft | Cascade polymer complexes, process for their production and pharmaceutical agents containing said complexes |
GB9624822D0 (en) | 1996-11-28 | 1997-01-15 | Nycomed Imaging As | Method |
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