DE3443252A1 - Dextran-magnetite complexes for NMR diagnosis - Google Patents

Dextran-magnetite complexes for NMR diagnosis

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Publication number
DE3443252A1
DE3443252A1 DE19843443252 DE3443252A DE3443252A1 DE 3443252 A1 DE3443252 A1 DE 3443252A1 DE 19843443252 DE19843443252 DE 19843443252 DE 3443252 A DE3443252 A DE 3443252A DE 3443252 A1 DE3443252 A1 DE 3443252A1
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Germany
Prior art keywords
dextran
magnetite
complexes
complex
nmr
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Withdrawn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
DE19843443252
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German (de)
Inventor
Heinz Dr. Gries
Wolfgang Dr. Mützel
Hanns-Joachim Dr. 1000 Berlin Weinmann
Christian Dr. Zurth
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
Original Assignee
Schering AG
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 Schering AG filed Critical Schering AG
Priority to DE19843443252 priority Critical patent/DE3443252A1/en
Priority to PT81498A priority patent/PT81498B/en
Priority to NZ214228A priority patent/NZ214228A/en
Priority to AU50225/85A priority patent/AU583070B2/en
Priority to ES549144A priority patent/ES8703153A1/en
Priority to AT85730153T priority patent/ATE56880T1/en
Priority to GR852815A priority patent/GR852815B/el
Priority to EP85730153A priority patent/EP0186616B2/en
Priority to DE8585730153T priority patent/DE3579899D1/en
Priority to CA000496054A priority patent/CA1252950A/en
Priority to IE293585A priority patent/IE58324B1/en
Priority to DK198505417A priority patent/DK174946B1/en
Priority to NO854679A priority patent/NO167077C/en
Priority to JP60262727A priority patent/JP2740782B2/en
Publication of DE3443252A1 publication Critical patent/DE3443252A1/en
Priority to ES557099A priority patent/ES8704352A1/en
Priority to US08/484,309 priority patent/US5746999A/en
Priority to US08/997,748 priority patent/US20020064502A1/en
Priority to US10/105,462 priority patent/US20020136693A1/en
Withdrawn legal-status Critical Current

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    • 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
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1887—Agglomerates, clusters, i.e. more than one (super)(para)magnetic microparticle or nanoparticle are aggregated or entrapped in the same maxtrix
    • 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
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • A61K49/0414—Particles, beads, capsules or spheres
    • 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
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
    • A61K49/1863—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
    • C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch
    • C08B30/18—Dextrin, e.g. yellow canari, white dextrin, amylodextrin or maltodextrin; Methods of depolymerisation, e.g. by irradiation or mechanically
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0021—Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
    • G01N2400/10—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • G01N2400/12—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar
    • G01N2400/14—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar alpha-D-Glucans, i.e. having alpha 1,n (n=3,4,6) linkages between saccharide units, e.g. pullulan
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
    • G01N2400/10—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • G01N2400/12—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar
    • G01N2400/14—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar alpha-D-Glucans, i.e. having alpha 1,n (n=3,4,6) linkages between saccharide units, e.g. pullulan
    • G01N2400/22—Dextran
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2446/00—Magnetic particle immunoreagent carriers
    • G01N2446/20—Magnetic particle immunoreagent carriers the magnetic material being present in the particle core
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2446/00—Magnetic particle immunoreagent carriers
    • G01N2446/30—Magnetic particle immunoreagent carriers the magnetic material being dispersed in the polymer composition before their conversion into particulate form
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2446/00—Magnetic particle immunoreagent carriers
    • G01N2446/80—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids
    • G01N2446/86—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids the coating being pre-functionalised for attaching immunoreagents, e.g. aminodextran

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nanotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Radiology & Medical Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Diagnostic agents which contain a physiologically tolerable dextran-magnetite complex are suitable for use in NMR diagnosis.

Description

Dextran-Magnetit-Komplexe fürDextran-magnetite complexes for

die NMR-Diagnostik Die Erfindung betrifft diagnostische Mittel zur Anwendung in der NMR-Diagnostik, die einen physiologisch verträglichen Dextran-Magnetit-Komplex enthalten.NMR diagnostics The invention relates to diagnostic Means for use in NMR diagnostics which have a physiologically compatible Contains dextran magnetite complex.

Solche Komplexe von Magnetit (Fe304) mit Dextranen sind zum Beispiel beschrieben in den US-Patenten 4,101,435 und 4, 452,773. Sie bilden in Wasser stabile Sole, die aufgrund ihrer magnetischen Eigenschaften vielfältige Verwendung finden können. So sind sie unter anderem als Drug-Carrier (vor allem für Cytotoxika bei der Tumorbehandlung), als Agens zur Messung des Blutstroms, als Marker in der Scanning/transmission-Elektronenmikroskopie, zur Kennzeichnung und Abtrennung von Zellen und Biomolekülen (zum Beispiel eines Antigens aus einer Antigenmischung, indem man Partikel benutzt, die kovalent an den entsprechenden Antikörper gebunden sind), sowie auch zur Anwendung auf mechanischem Gebiet (zum Beispiel als magnetische Flüssigkeit) geeignet.Such complexes of magnetite (Fe304) with dextrans are for example described in U.S. Patents 4,101,435 and 4,452,773. They form stable in water Brines, which are used in a variety of ways due to their magnetic properties can. So they are among other things as a drug carrier (especially for cytotoxics tumor treatment), as an agent for measuring blood flow, as a marker in scanning / transmission electron microscopy, to identify and separate cells and biomolecules (for example a Antigens from a mixture of antigens by using particles that are covalently attached the corresponding antibodies are bound), as well as for use on mechanical Area (for example as a magnetic fluid) suitable.

Ferner ist Dextran-Magnetit als Relaxationsagens zur Messung des Wasseraustausches an Erythrozytenmembranen vorgeschlagen worden (Biochem. and Biophys. Res.Comm. 97, 114 (1980)).Furthermore, dextran magnetite is used as a relaxation agent for measuring the water exchange on erythrocyte membranes has been proposed (Biochem. and Biophys. Res.Comm. 97, 114 (1980)).

Es wurde nun gefunden, daß die erfindungsgemäßen Mittel überraschenderweise die vielfältigen Voraussetzungen für die Eignung als Kontrastmittel für die NMR-Diagnostik erfüllen. (Eine ausführliche Diskussion dieser Voraussetzungen findet sich in der Europäischen Patentanmeldung 71 564 und in der Deutschen Patentanmeldung P 34 01 052.1).It has now been found that, surprisingly, the agents according to the invention the diverse requirements for suitability as a contrast agent for NMR diagnostics fulfill. (A detailed discussion of these requirements can be found in the European patent application 71 564 and in German patent application P 34 01 052.1).

So sind sie hervorragend dazu geeignet, nach enteraler oder parenteraler Applikation durch Veränderung der Signalintensität das mit Hilfe des Kernspintomographen erhaltene Bild in seiner Aussagekraft zu verbessern. Ferner zeigen sie die hohe Wirksamkeit, die notwendig ist, um den Körper mit möglichst geringen Mengen an Kontrastmittel zu belasten, und die gute Verträglichkeit, die notwendig ist, um den nicht-invasiven Charakter der Untersuchung aufrechtzuerhalten.So they are ideally suited for enteral or parenteral Application by changing the signal intensity that with help the image obtained from the magnetic resonance tomograph to improve its informative value. Further they show the high effectiveness that is necessary to keep the body with as possible load small amounts of contrast medium, and the good tolerance that is necessary to maintain the non-invasive nature of the investigation.

Als besonders günstig ist hierbei anzusehen, daß als Träger der magnetischen Eigenschaften das Eisen fungiert, ein physiologisch unbedenkliches Element, das für den menschlichen Organismus sogar essentiell ist. Da überraschenderweise im Vergleich zu allen vorbekannten Kontrastmitteln die wirksame Dosis außerordentlich niedrig ist, ergibt sich ein sehr hoher Sicherheitsabstand für die Verwendung der Komplexe in vivo.It is particularly advantageous that the magnetic carrier is used as a carrier Properties the iron acts, a physiologically harmless element that is even essential for the human organism. Since, surprisingly, in the Compared to all previously known contrast media, the effective dose is extraordinary is low, there is a very high safety margin for using the Complexes in vivo.

Die gute Wasserlöslichkeit der erfindungsgemäßen Mittel erlaubt es, hochkonzentrierte Lösungen herzustellen, um die Volumenbelastung des Kreislaufs in vertretbaren Grenzen zu halten und die Verdünnung durch die Körperflüssigkeit auszugleichen.The good water solubility of the agents according to the invention allows Prepare highly concentrated solutions to reduce the volume load on the circulatory system to keep within reasonable limits and the dilution by the body fluid balance.

Weiterhin weisen die erfindungsgemäßen Mittel nicht nur eine hohe Stabilität in vitro, sondern auch eine überraschend hohe Stabilität in vivo auf.Furthermore, the agents according to the invention not only have a high Stability in vitro, but also a surprisingly high stability in vivo.

Ein besonderer Vorzug der erfindungsgemäßen Mittel ist es, daß mit ihnen zum ersten Mal gut verträgliche Kontrastmittel für die bildliche Darstellung von Tumoren der Leber und Milz zur Verfügung stehen.A particular advantage of the agents according to the invention is that with them for the first time well-tolerated contrast media for the visual representation from tumors of the liver and spleen are available.

Für die parenterale Applikation erfolgt die Herstellung der erfindungsgemäßen diagnostischen Mittel in an sich bekannter Weise, indem man das den Komplex enthaltende Sol mit physiologischer Kochsalzlösung auf die gewünschte Eisenkonzentration einstellt und anschließend sterilisiert.The preparation according to the invention is carried out for parenteral administration diagnostic means in a manner known per se, by the complex containing Sol with physiological Saline to the desired iron concentration adjusted and then sterilized.

Für die enterale Verabreichung wird das den Komplex enthaltende Sol mit einem oder mehreren der in der Galenik üblichen Hilfsstoffen (z.B. Methylcellulose, Lactose, Mannit) und/oder Tensiden (z.B. Lecithine, Tweens , Myrj (R)) und/oder Aromastoffen (z.B. ätherischen ölen) zur Geschmackskorrektur gemischt.For enteral administration, the sol containing the complex with one or more of the auxiliary substances commonly used in galenicals (e.g. methyl cellulose, Lactose, mannitol) and / or surfactants (e.g. lecithins, tweens, Myrj (R)) and / or Flavors (e.g. essential oils) mixed to correct the taste.

Die erfindungsgemäßen dieagnostischen Mittel enthalten 1 uMol bis 1 Mol, vorzugsweise 0,1 bis 100 mMol Eisen pro Liter und werden in der Regel in Mengen von 0,001 bis 100 uMol, vorzugsweise 0,1 bis 10 uMol Eisen pro kg Körpergewicht, dosiert. Sie sind zur enteralen und parenteralen Applikation bestimmt.The diagnostic agents of the present invention contain 1 µmole to 1 mol, preferably 0.1 to 100 mmol of iron per liter and are usually in Amounts of 0.001 to 100 µmoles, preferably 0.1 to 10 µmoles of iron per kg of body weight, dosed. They are intended for enteral and parenteral administration.

Die folgenden Ausführungsbeispiele dienen zur weiteren Erläuterung der Erfindung.The following exemplary embodiments serve for further explanation the invention.

Beispiel 1 112 mg Dextran-Magnetit-Komplex (bezogen von Fa. Meito Sangyo, Japan) werden unter Rühren in 20 ml einer 0,9%gen Kochsalzlösung eingetragen. Das erhaltene Sol wird in Ampullen abgefüllt und hitzesterilisiert.Example 1 112 mg of dextran-magnetite complex (obtained from Meito Sangyo, Japan) are introduced into 20 ml of a 0.9% saline solution with stirring. The sol obtained is filled into ampoules and heat-sterilized.

Beispiel 2 Ein Granulat, hergestellt aus 12 mg Dextran-Magnetit-Komplex, (bezogen von Fa Meito Sangyo, Japan) 2,42 g Tromethamin, 45 g Mannit und 10 g Tylose, wird in 1000 ml Aqua dest.Example 2 A granulate made from 12 mg of dextran-magnetite complex, (obtained from Fa Meito Sangyo, Japan) 2.42 g tromethamine, 45 g mannitol and 10 g tylose, is in 1000 ml of distilled water.

eingerührt für die enterale Applikation verwendet.used for enteral application.

Claims (4)

Patentansprüche 1.) Diagnostische Mittel zur Anwendung in der NMR-Diagnostik, dadurch gekennzeichnet, daß sie einen physiologisch verträglichen Dextran-Magnetit-Komplex enthalten. Claims 1.) Diagnostic means for use in NMR diagnostics, characterized in that it contains a physiologically acceptable dextran-magnetite complex contain. 2.) Diagnostische Mittel gemäß Patentanspruch 1, dadurch gekennzeichnet, daß sie pro Liter 1 pMol bis 1 Mol Eisen enthalten.2.) Diagnostic means according to claim 1, characterized in that that they contain 1 pmole to 1 mole of iron per liter. 3.) Verfahren zur Herstellung der diagnostischen Mittel gemäß Patentanspruch 1 und 2, dadurch gekennzeichnet, daß man den in Wasser oder physiologischer Salzlösung suspendierten Komplex mit den in der Galenik üblichen Zusätzen bzw. Stabilisatoren in eine für die enterale oder parenterale Applikation geeignete Form bringt.3.) Process for the production of the diagnostic agent according to claim 1 and 2, characterized in that the in water or physiological saline solution suspended complex with the additives or stabilizers customary in galenicals brings into a form suitable for enteral or parenteral administration. 4.) Verwendung von Dextran-Magnetit-Komplexen für die NMR-Diagnos tik.4.) Use of dextran-magnetite complexes for NMR diagnosis tik.
DE19843443252 1984-11-23 1984-11-23 Dextran-magnetite complexes for NMR diagnosis Withdrawn DE3443252A1 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
DE19843443252 DE3443252A1 (en) 1984-11-23 1984-11-23 Dextran-magnetite complexes for NMR diagnosis
PT81498A PT81498B (en) 1984-11-23 1985-11-15 METHOD FOR PREPARING COMPOSITIONS FOR DIAGNOSTICS CONTAINING MAGNETIC PARTICLES
NZ214228A NZ214228A (en) 1984-11-23 1985-11-18 Agents for in vivo diagnostic use containing magnetic particles
AU50225/85A AU583070B2 (en) 1984-11-23 1985-11-19 Magnetic particles for diagnostic purposes
ES549144A ES8703153A1 (en) 1984-11-23 1985-11-21 Magnetic particles for diagnostic purposes.
AT85730153T ATE56880T1 (en) 1984-11-23 1985-11-21 MAGNETIC PARTICLES FOR DIAGNOSTICS.
GR852815A GR852815B (en) 1984-11-23 1985-11-21
EP85730153A EP0186616B2 (en) 1984-11-23 1985-11-21 Magnetic particles for diagnostic purposes
DE8585730153T DE3579899D1 (en) 1984-11-23 1985-11-21 MAGNETIC PARTICLES FOR DIAGNOSTICS.
CA000496054A CA1252950A (en) 1984-11-23 1985-11-22 Magnetic particles for diagnostic purposes
IE293585A IE58324B1 (en) 1984-11-23 1985-11-22 Magnetic Particles for Diagnostic Purposes
DK198505417A DK174946B1 (en) 1984-11-23 1985-11-22 Use of magnetic particles for diagnostics
NO854679A NO167077C (en) 1984-11-23 1985-11-22 Diagnostic agents for use in in vivo NMR diagnostics, X-ray diagnostics or ultrasound diagnostics.
JP60262727A JP2740782B2 (en) 1984-11-23 1985-11-25 In vivo contrast NMR diagnostic medicine
ES557099A ES8704352A1 (en) 1984-11-23 1986-09-30 Magnetic particles for diagnostic purposes.
US08/484,309 US5746999A (en) 1984-11-23 1995-06-07 Magnetic particles for diagnostic purposes
US08/997,748 US20020064502A1 (en) 1984-11-23 1997-12-24 Magnetic particles for diagnostic purposes
US10/105,462 US20020136693A1 (en) 1984-11-23 2002-03-27 Magnetic particles for diagnostic purposes

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DE19843443252 DE3443252A1 (en) 1984-11-23 1984-11-23 Dextran-magnetite complexes for NMR diagnosis

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4770183A (en) * 1986-07-03 1988-09-13 Advanced Magnetics Incorporated Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
DE3709851A1 (en) * 1987-03-24 1988-10-06 Silica Gel Gmbh Adsorptions Te NMR DIAGNOSTIC LIQUID COMPOSITIONS
US4951675A (en) * 1986-07-03 1990-08-28 Advanced Magnetics, Incorporated Biodegradable superparamagnetic metal oxides as contrast agents for MR imaging
WO1991001148A1 (en) 1989-07-21 1991-02-07 Nycomed As Contrast medium composition
EP0444194A1 (en) * 1988-08-19 1991-09-04 Meito Sangyo Kabushiki Kaisha Agent for thermotherapy
US5314681A (en) * 1988-12-23 1994-05-24 Nycomed Innovation Ab Composition of positive and negative contrast agents for electron spin resonance enhanced magnetic resonance imaging
DE4309333A1 (en) * 1993-03-17 1994-09-22 Silica Gel Gmbh Superparamagnetic particles, process for their production and use thereof
DE10154016B4 (en) * 2001-10-26 2004-02-12 Berlin Heart Ag Magnetic fluid and process for its manufacture
US8669236B2 (en) 2005-05-12 2014-03-11 The General Hospital Corporation Biotinylated compositions
DE102014106603A1 (en) 2014-05-12 2015-11-12 Verein zur Förderung von Innovationen durch Forschung, Entwicklung und Technologietransfer e.V. (Verein INNOVENT e.V.) Method and apparatus for depleting circulating tumor cells from a cell suspension
US10532104B2 (en) 2012-08-31 2020-01-14 The General Hospital Corporation Biotin complexes for treatment and diagnosis of Alzheimer'S disease

Citations (4)

* Cited by examiner, † Cited by third party
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US4951675A (en) * 1986-07-03 1990-08-28 Advanced Magnetics, Incorporated Biodegradable superparamagnetic metal oxides as contrast agents for MR imaging
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EP0444194A4 (en) * 1988-08-19 1991-12-04 Meito Sangyo Kabushiki Kaisha Agent for thermotherapy
US5314681A (en) * 1988-12-23 1994-05-24 Nycomed Innovation Ab Composition of positive and negative contrast agents for electron spin resonance enhanced magnetic resonance imaging
WO1991001148A1 (en) 1989-07-21 1991-02-07 Nycomed As Contrast medium composition
DE4309333A1 (en) * 1993-03-17 1994-09-22 Silica Gel Gmbh Superparamagnetic particles, process for their production and use thereof
DE10154016B4 (en) * 2001-10-26 2004-02-12 Berlin Heart Ag Magnetic fluid and process for its manufacture
US8669236B2 (en) 2005-05-12 2014-03-11 The General Hospital Corporation Biotinylated compositions
US10532104B2 (en) 2012-08-31 2020-01-14 The General Hospital Corporation Biotin complexes for treatment and diagnosis of Alzheimer'S disease
DE102014106603A1 (en) 2014-05-12 2015-11-12 Verein zur Förderung von Innovationen durch Forschung, Entwicklung und Technologietransfer e.V. (Verein INNOVENT e.V.) Method and apparatus for depleting circulating tumor cells from a cell suspension
EP2944686A1 (en) 2014-05-12 2015-11-18 Verein zur Förderung von Innovationen durch Forschung, Entwicklung und Technologietransfer e.V. (Verein INNOVENT e.V.) Method and device for the removal of circulating tumor cells from a cell suspension

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