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Use of bile acid derivatives conjugated with metal ion chelated complexes for the diagnostic assessment of microvascular permeability

a technology of microvascular permeability and bile acid derivatives, which is applied in the field of use of bile acid derivatives conjugated with metal ion chelated complexes for the diagnostic assessment of microvascular permeability, can solve the problems of no one of these macromolecular contrast agents likely to enter clinical trials, general unsettled solid tumor structure, and fundamental chaos

Inactive Publication Date: 2007-03-15
BRACCO IMAGINIG SPA +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The structure of solid tumors is generally unsettled, fundamentally chaotic, in contrast to the elegant and ordered anatomical design of normal tissues and organs.
Moreover, when a tumor is present, generally, the capillary endothelium is also injured.
However, no one of these macromolecular contrast agents will be likely to enter clinical trials because of incomplete elimination and potential for toxicity or immunogenic response they have shown (JMRI 1997; 7:331-338).
The teaching emerging from the results of these studies is that low molecular weight contrast agents are not able to differentiate a healthy tissue from a pathologic tissue including injured or hyperpermeable microvessels.

Method used

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  • Use of bile acid derivatives conjugated with metal ion chelated complexes for the diagnostic assessment of microvascular permeability
  • Use of bile acid derivatives conjugated with metal ion chelated complexes for the diagnostic assessment of microvascular permeability
  • Use of bile acid derivatives conjugated with metal ion chelated complexes for the diagnostic assessment of microvascular permeability

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Embodiment Construction

[0026] The present invention relates to the new use of a particular selection of compounds having a molecular weight lower than 5000 Dalton, preferably between 4500 to 500 and more preferably between 3000 to 500 Dalton which include in their structure at least a biliary acid residue, for the preparation of contrastographic formulations for the diagnostic visualization of microvascularized systems, in particular wherein the relative tissue plasma volume is determined and / or the microvessels permeability as well as integrity are measured.

[0027] In particular, the invention relates to the new use of a class of compounds including in their molecular structure at least one, and preferably one, biliary acid residue and at least one, but not more than two, chelated complex units of bi or trivalent paramagnetic metal ions, as well as the salts thereof with physiologically compatible organic bases selected from primary, secondary, tertiary amines or basic amino acids, or with inorganic base...

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Abstract

The use of contrast agents of molecular weight lower than 5000 Dalton and including at least one residue of a biliary acid for the preparation of diagnostic contrast compositions for the microvascular permeability assessment is disclosed.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application is a continuation-in-part of application Ser. No. 10 / 257,533 filed Oct. 24, 2002, now U.S. Ser. No. ______, which in turn is a U.S. national phase of PCT / EP01 / 04324 filed Apr. 17, 2001, which claims priority of IT MI2000A000899 filed Apr. 21, 2000, the disclosures of which are hereby incorporated by reference. [0002] The present invention relates to the use of metal ion chelated complexes for the preparation of pharmaceutical formulations for the diagnostic assessment of microvascularized systems.BACKGROUND OF THE INVENTION [0003] The structure of solid tumors is generally unsettled, fundamentally chaotic, in contrast to the elegant and ordered anatomical design of normal tissues and organs. Solid tumor and, in particular, malignant tumor microcirculation differs profoundly from that of a normal organ. The variation of the capillary density is mainly due to the vascular endothelial grown factor (VEGF), also known as vasc...

Claims

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Application Information

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IPC IPC(8): A61K49/10A61K49/00A61K49/08A61K51/04
CPCA61K49/085A61K51/0497A61K49/10
Inventor CAVAGNA, FRIEDRICHROBERTS, TIMOTHY P.L.
Owner BRACCO IMAGINIG SPA
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