EP0510030A1 - Complexes d'elements de transition pour diagnostic par resonance magnetique - Google Patents

Complexes d'elements de transition pour diagnostic par resonance magnetique

Info

Publication number
EP0510030A1
EP0510030A1 EP19910901732 EP91901732A EP0510030A1 EP 0510030 A1 EP0510030 A1 EP 0510030A1 EP 19910901732 EP19910901732 EP 19910901732 EP 91901732 A EP91901732 A EP 91901732A EP 0510030 A1 EP0510030 A1 EP 0510030A1
Authority
EP
European Patent Office
Prior art keywords
complexes
transition metal
cooh
diagnostics
general formula
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Withdrawn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
EP19910901732
Other languages
German (de)
English (en)
Inventor
Uwe Krüger
Herbert Rupp
Klaus-Dieter Beller
Hans-Peter Kley
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.)
Takeda GmbH
Original Assignee
Byk Gulden Lomberg Chemische Fabrik GmbH
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 Byk Gulden Lomberg Chemische Fabrik GmbH filed Critical Byk Gulden Lomberg Chemische Fabrik GmbH
Publication of EP0510030A1 publication Critical patent/EP0510030A1/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Withdrawn legal-status Critical Current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

Definitions

  • the invention relates to new contrast media for MR diagnostics.
  • EP-A-0303555 discloses complexes of ethanolamine phosphoric acid with iron (III) and manganese (II) which are intended for prophylaxis and therapy.
  • EP-A-0173163 proposes the use of metal complexes with phosphonylorganophosphates for MR diagnostics.
  • EP-A-0290047 describes measurement tall complexes of dipyridoxyl phosphoric acids as MR contrast agents.
  • EP-A 0284549 proposes the use of magnetic liquids to increase the relaxivity in MR-diagnostic examinations. Due to the strongly relaxing effect of the superparamagnetic particles contained in the magnetic liquids, a so-called negative contrast can also be achieved by signal cancellation.
  • EP-A 0190676 discloses all-cis-1,3,5-triamino-2,4,6-cyclohexanetriol derivatives which are suitable for complexing metal cations, in particular iron (III).
  • the object of the present invention is to provide new contrast media for MR diagnostics, which are characterized by high complex stability, good water solubility at physiological pH values, strong relaxivity and by a pronounced organ specificity combined with reduced side effects and distinguish faster excretion.
  • the invention relates to the use of complexes of the compounds of the general formula I,
  • Rl, R2, R3, R4, R5 and R6 are the same or different and
  • R7 represents hydrogen, COOH and PO (OH), with paramagnetic transition metal cations and their salts with cations of strong bases for the production of agents for MR diagnostics.
  • R7 represent hydrogen, COOH and PO (OH).
  • R2, R4 and R6 C (0) CH, C (0) C H, CH COOH, CH CH COOH, CH P (0) (OH),
  • Suitable transition metal cations are the cations of the transition metals of atomic numbers 21 to 29, 42 and 44 and the cations of the lanthanide elements of atomic numbers 57 to 70, gadolinium being preferred by the lanthanide elements.
  • iron (III) -all-cis-1,3,5-tris is particularly preferred.
  • the first preferred complex shows a longitudinal relaxivity TR of 2J058 [sec mmol] and a transverse relaxivity TR of 1.945 [sec mmol].
  • the second complex shows values of 4,113 (TR) and 4,340 (TR).
  • the sodium and N-methylglucamine salts are preferred as salts of the complexes used according to the invention.
  • Si show a strong relaxivity with regard to both T1 and T2, so that they can also be used for signal extinction similar to magnetite particles.
  • Contrast agents for MR diagnostics contain one or more of the complexes of the general formula I and, if desired, customary additives.
  • the complexes are prepared in a manner known per se by adding salts of paramagnetic transition metal ions in water and / or alcohol, such as
  • Methanol, ethanol, etc. dissolves and, if necessary, with the appropriate amount of ligand, while stirring at 50 ° C. to 120 ° C., until the reaction is complete. If the complex formed is insoluble in the solvent used, it crystallizes and can be filtered off. If the complex is soluble in the solvent used, it can be isolated by evaporating the solution to dryness. The complex compound obtained is then dissolved or suspended in water and mixed with the desired inorganic or organic base until the neutral point is reached. After filtration of undissolved portions, the solution is evaporated and the desired complex salt is obtained as residue. The salts of the complexes are obtained, for example, by reaction with strong bases.
  • the new contrast media are prepared in a manner known per se by dissolving the complexes and / or their salts in water or physiological salt solution and, if desired, additives customary in galenics, such as, for example, physiologically compatible buffer solutions (for example sodium dihydro gene phosphate solution), albumin and the like, and the solution is sterilized.
  • physiologically compatible buffer solutions for example sodium dihydro gene phosphate solution
  • albumin for example, albumin and the like
  • the solutions can be filled as such into ampoules or freeze-dried to a soluble powder.
  • the aqueous solutions are adjusted to a pH with sufficient local tissue tolerance, for example to a pH of 7 to 9.
  • the aqueous solutions are administered orally or parenterally, in particular intravascularly.
  • aqueous solutions which contain the paramagnetic complex in a concentration of 30 to 200 mmol / liter. Approximately 1 to 100 ⁇ mol of the complex is administered per kg body weight per application. For an adult, a dose of 1 to 50 mmol proves to be appropriate for IV use.

Landscapes

  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Des complexes des composés de formule générale (I), dans laquelle R1, R2, R3, R4, R5 et R6 sont similaires ou différents et représentent hydrogène, méthyle et X-(CH2)n-R7, où X représente CH2 et C(O), n représente un nombre entier de 1 à 4, et R7 représente hydrogène, COOH et PO(OH)2, avec des cations d'éléments de transition paramagnétiques et leurs sels avec des cations fortement basiques, s'utilisent dans la fabrication de substances servant au diagnostic par résonance magnétique.
EP19910901732 1990-01-09 1991-01-08 Complexes d'elements de transition pour diagnostic par resonance magnetique Withdrawn EP0510030A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH6290A CH679742A5 (fr) 1990-01-09 1990-01-09
CH62/90 1990-01-09

Publications (1)

Publication Number Publication Date
EP0510030A1 true EP0510030A1 (fr) 1992-10-28

Family

ID=4178448

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19910901732 Withdrawn EP0510030A1 (fr) 1990-01-09 1991-01-08 Complexes d'elements de transition pour diagnostic par resonance magnetique

Country Status (5)

Country Link
EP (1) EP0510030A1 (fr)
JP (1) JPH05504343A (fr)
AU (1) AU7044791A (fr)
CH (1) CH679742A5 (fr)
WO (1) WO1991010454A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4028139A1 (de) * 1990-09-05 1992-03-12 Hausmann Ag Labor Verwendung der komplexe radioaktiver metallionen mit all-cis-1,3,5-triamino-2,4,6-cyclohexantriol und seinen derivaten fuer roentgendiagnostische zwecke und in der tumortherapie sowie zur herstellung von mitteln fuer roentgendiagnostische zwecke und fuer die tumortherapie
JP2894879B2 (ja) * 1991-10-04 1999-05-24 日本メジフィジックス株式会社 診断用造影剤
JP5172162B2 (ja) 2006-08-25 2013-03-27 株式会社日立ハイテクノロジーズ 欠陥検査装置
CN104321082A (zh) 2012-05-18 2015-01-28 拜耳医药股份有限公司 用于x射线成像的双氮杂肌醇重金属络合物
EP2796152A1 (fr) 2013-04-25 2014-10-29 Bayer Pharma Aktiengesellschaft Complexes au Bis Azainositol Hafnium asymétriques pour imagerie par rayons X
EP2873670A1 (fr) 2013-11-14 2015-05-20 Bayer Pharma Aktiengesellschaft Complexes de zirconium bis azainositol pour imagerie par rayons X

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3129906C3 (de) * 1981-07-24 1996-12-19 Schering Ag Paramagnetische Komplexsalze, deren Herstellung und Mittel zur Verwendung bei der NMR-Diagnostik
DE3503614A1 (de) * 1985-02-02 1986-08-07 Laboratorien Hausmann AG, St. Gallen All-cis-1,3,5-triamino-2,4,6-cyclohexantriol-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische praeparate
DE3625417C2 (de) * 1986-07-28 1998-10-08 Schering Ag Tetraazacyclododecan-Derivate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9110454A1 *

Also Published As

Publication number Publication date
CH679742A5 (fr) 1992-04-15
AU7044791A (en) 1991-08-05
WO1991010454A1 (fr) 1991-07-25
JPH05504343A (ja) 1993-07-08

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