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EP2111236A2 - Nouveaux complexes de polymères en cascade, procédés de fabrication et agents pharmaceutiques contenant ces complexes - Google Patents

Nouveaux complexes de polymères en cascade, procédés de fabrication et agents pharmaceutiques contenant ces complexes

Info

Publication number
EP2111236A2
EP2111236A2 EP08701131A EP08701131A EP2111236A2 EP 2111236 A2 EP2111236 A2 EP 2111236A2 EP 08701131 A EP08701131 A EP 08701131A EP 08701131 A EP08701131 A EP 08701131A EP 2111236 A2 EP2111236 A2 EP 2111236A2
Authority
EP
European Patent Office
Prior art keywords
mmol
coch
cascade
ethoxy
optionally
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.)
Withdrawn
Application number
EP08701131A
Other languages
German (de)
English (en)
Inventor
Heribert Schmitt-Willich
Heiko Schirmer
Bernd Misselwitz
Hanns-Joachim Weinmann
Peter Caravan
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.)
Bayer Pharma AG
Epix Pharmaceuticals Inc
Original Assignee
Bayer Schering Pharma AG
Epix Pharmaceuticals 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 Bayer Schering Pharma AG, Epix Pharmaceuticals Inc filed Critical Bayer Schering Pharma AG
Publication of EP2111236A2 publication Critical patent/EP2111236A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • 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
    • A61K49/12—Macromolecular compounds
    • A61K49/124—Macromolecular compounds dendrimers, dendrons, hyperbranched compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/02—Polyamines

Definitions

  • the complexing agent residues K are described by the general formulas IA, IB and IC:
  • Suitable HSA-binding groups R are given by way of example:
  • the cascade polymer complexes according to the invention contain at least 4 ions of an element of the abovementioned atomic number.
  • the cascade polymer complexes according to the invention have surprising properties compared to known cascade polymer complexes, as described in the European patent EP 0 836 485. These surprising properties allow an even more flexible choice of imaging times and a more favorable signal-to-background ratio, especially at certain imaging times.
  • Particularly surprising in comparison to the known cascade polymer complexes from EP 0 836 485 is, above all, that although the cascade polymer complexes according to the invention presented here have one polymer arm less than the known cascade complexes and are therefore rather smaller in comparison Thus, these should tend to extravasation, the novel cascade polymer complexes according to the invention even have a significantly improved residence time in the blood.
  • the complexes and complexing agents of the general formula I 1 A and I 1 B are prepared by or analogously to the instructions described in the experimental section or by methods known from the literature, see, for example, European Patent Applications Nos. 0 512 661, 0430 863, 0 255 471 and 0 565 930.
  • the preparation of the pharmaceutical compositions according to the invention is likewise carried out in a manner known per se by suspending or dissolving the complex compounds according to the invention in aqueous medium, if appropriate with addition of the additives customary in galenicals, and then optionally sterilizing the suspension or solution.
  • suitable additives are, for example, physiologically acceptable buffers (such as tromethamine), additions of complexing agents or weak complexes (such as diethylenetriaminepentaacetic acid or the corresponding Ca-cascade polymer complexes) or, if necessary, electrolytes such as sodium chloride or, if necessary - Antioxidants such as ascorbic acid.
  • the compounds according to the invention are particularly suitable for use as coronary angiographic contrast agents and their use in NMR diagnosis by means of higher Magnetic fields such as 1.5 or 3 Tesla, as offered by modern NMR devices.
  • the compounds according to the invention are also suitable for the differentiation of malignant and benign tumors in areas without a blood-brain barrier.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Radiology & Medical Imaging (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne de nouveaux complexes de polymères en cascade, des agents contenant ces complexes, l'utilisation des complexes dans le diagnostic par IRM, et des procédés de fabrication de ces compositions et agents. Les complexes de polymères en cascade complexants sont représentés par la formule (I) : R - L - A -{ X - [ Y - ( Z - { W - K<SUB>w </SUB>}<SUB>z</SUB> )<SUB>y</SUB> ]<SUB>x</SUB>}<SUB>a-1</SUB>, dans laquelle R est une unité liant HSA; L est un lieur ou une liaison; A est un noyau de cascade azoté de multiplicité de base a; X et Y sont indépendamment l'un de l'autre une liaison directe ou une unité de production de cascade de multiplicité de reproduction x ou y; Z et W sont indépendamment l'un de l'autre une liaison directe ou une unité de production de cascade de multiplicité de reproduction z ou w; K est le reste d'un complexant; a est 2 à 12; et x, y, z et w sont indépendamment l'un de l'autre 1 à 4, à la condition qu'exactement une multiplicité de la multiplicité de base a du noyau de cascade A représente exactement une zone de liaison à L, et que les complexes de polymères en cascade dans les restes de complexants K contiennent au total 4 ions d'un élément de numéro atomique 20 à 29, 39, 42 à 44 ou 57 à 83, ainsi qu'éventuellement des cations de bases anorganiques et/ou organiques, des acides aminés ou des amides d'acides aminés.
EP08701131A 2007-01-18 2008-01-16 Nouveaux complexes de polymères en cascade, procédés de fabrication et agents pharmaceutiques contenant ces complexes Withdrawn EP2111236A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007002726A DE102007002726A1 (de) 2007-01-18 2007-01-18 Neue Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel
PCT/EP2008/000285 WO2008087017A2 (fr) 2007-01-18 2008-01-16 Nouveaux complexes de polymères en cascade, procédés de fabrication et agents pharmaceutiques contenant ces complexes

Publications (1)

Publication Number Publication Date
EP2111236A2 true EP2111236A2 (fr) 2009-10-28

Family

ID=39560934

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08701131A Withdrawn EP2111236A2 (fr) 2007-01-18 2008-01-16 Nouveaux complexes de polymères en cascade, procédés de fabrication et agents pharmaceutiques contenant ces complexes

Country Status (8)

Country Link
US (1) US20080213187A1 (fr)
EP (1) EP2111236A2 (fr)
JP (1) JP2010516643A (fr)
KR (1) KR20090110838A (fr)
CN (1) CN101657219A (fr)
CA (1) CA2676313A1 (fr)
DE (1) DE102007002726A1 (fr)
WO (1) WO2008087017A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110038805A1 (en) * 2008-04-18 2011-02-17 Andreas Meijer Compounds comprising paramagnetic chelates arranged around a central core and their use in magneto resonance imaging and spectroscopy
EP3101012A1 (fr) 2015-06-04 2016-12-07 Bayer Pharma Aktiengesellschaft Nouveaux composés de chélate de gadolinium pour une utilisation dans l'imagerie par résonance magnétique
RU2755181C2 (ru) 2016-11-28 2021-09-14 Байер Фарма Акциенгезельшафт Новые хелатные соединения гадолиния с высокой релаксивностью для применения в магнитно-резонансной визуализации
SG11202104657RA (en) 2018-11-23 2021-06-29 Bayer Ag Formulation of contrast media and process of preparation thereof
CN115894181A (zh) * 2022-09-30 2023-04-04 渭南高新区海泰新型电子材料有限责任公司 一种环己烯基环己基二氟苯类液晶化合物的合成方法
CN116751260B (zh) * 2023-04-11 2024-05-28 苏州有诺真生物科技有限公司 一种通过级联聚合反应生成尺寸可控的通用多聚显色物的方法

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1203164A (fr) 1982-03-09 1986-04-15 Thomas J. Mckearn Conjugats d'anticorps
NL194579C (nl) 1983-01-21 2002-08-05 Schering Ag Diagnostisch middel.
US4707352A (en) 1984-01-30 1987-11-17 Enzo Biochem, Inc. Method of radioactively labeling diagnostic and therapeutic agents containing a chelating group
DK172629B1 (da) 1986-02-14 1999-03-22 Nihon Mediphysics Co Ltd Reaktive højmolekylære forbindelser med mindst én fri aminogruppe, højmolekylære forbindelser kombineret med et fysiologisk
DE3625417C2 (de) 1986-07-28 1998-10-08 Schering Ag Tetraazacyclododecan-Derivate
GB8801646D0 (en) 1988-01-26 1988-02-24 Nycomed As Chemical compounds
DE3806795A1 (de) 1988-02-29 1989-09-07 Schering Ag Polymer-gebundene komplexbildner, deren komplexe und konjugate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel
US5914095A (en) * 1989-04-07 1999-06-22 Salutar, Inc. Polychelants containg amide bonds
US5364613A (en) * 1989-04-07 1994-11-15 Sieving Paul F Polychelants containing macrocyclic chelant moieties
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
DE4115789A1 (de) 1991-05-10 1992-11-12 Schering Ag Makrocyclische polymer-komplexbildner, deren komplexe, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel
KR930019648A (ko) 1992-03-27 1993-10-18 도키 가츠유키 테트라아자시클로도덴칸 유도체 및 그의 용도
DE69533569T2 (de) * 1994-03-07 2006-01-05 Dendritic Nanotechnologies, Inc., Mt. Pleasant Bioaktive und/oder gezielte dendrimere-konjugate enthaltend genetisches material
DE4425857A1 (de) * 1994-07-07 1996-01-11 Schering Ag Kaskaden-Polymer-Komplexe, Verfahren zur ihrer Herstellung und diese enthaltende pharmazeutische Mittel
DE4445065A1 (de) * 1994-12-07 1996-06-13 Diagnostikforschung Inst Verfahren zur In-vivo-Diagnostik mittels NIR-Strahlung
TW319763B (fr) * 1995-02-01 1997-11-11 Epix Medical Inc
DE19525924A1 (de) 1995-07-04 1997-01-09 Schering Ag Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel
DE19549286A1 (de) * 1995-12-22 1997-06-26 Schering Ag Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel
DE19652386A1 (de) 1996-12-04 1998-06-10 Schering Ag Verfahren zur Herstellung von Metallkomplexcarbonsäureamiden
DE19926154A1 (de) * 1999-06-09 2000-12-14 Ktb Tumorforschungs Gmbh Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung
EP1757311B1 (fr) * 1999-12-24 2009-02-11 Genentech, Inc. Méthodes et compositions pour la prolongation de la demi-période d'élimination de composés bioactifs
CU23011A1 (es) * 2000-11-03 2004-12-17 Ct Ingenieria Genetica Biotech Método de obtención de estructuras antigénicas quemétodo de obtención de estructuras antigénicas que potencian la reactividad cruzada específica y su potencian la reactividad cruzada específica y su uso en formulaciones uso en formulaciones
US7985401B2 (en) * 2003-10-31 2011-07-26 The Regents Of The University Of California Peptides whose uptake by cells is controllable
WO2006029150A2 (fr) * 2004-09-03 2006-03-16 Alza Corporation Conjugue d'albumine forme de maniere endogene

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008087017A2 *

Also Published As

Publication number Publication date
DE102007002726A1 (de) 2008-07-31
WO2008087017A3 (fr) 2009-01-22
US20080213187A1 (en) 2008-09-04
WO2008087017A2 (fr) 2008-07-24
KR20090110838A (ko) 2009-10-22
CN101657219A (zh) 2010-02-24
JP2010516643A (ja) 2010-05-20
CA2676313A1 (fr) 2008-07-24

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Owner name: EPIX PHARMACEUTICALS, INC.

Owner name: BAYER PHARMA AKTIENGESELLSCHAFT

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