Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Molecular bilayer structure
Patent
1992-05-08
1994-10-18
Kumar, Shailendra
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Molecular bilayer structure
564153, 564156, 514616, A61K 4904, C07C23305
Patent
active
053566130
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to x-ray contrast agents and, more particularly, to novel nonionic x-ray contrast agents, radiological compositions containing such agents and methods for X-ray visualization utilizing such compositions.
Nonionic contrast agents for intravascular and central nervous system visualization are complex molecules. As is known, the iodine in the molecule provides opacification to the x-rays. The remainder of the molecule provides the framework for transport of the iodine atoms. However, the structural arrangement of the molecule is important in providing stability, solubility and biological safety in various organs. A stable carbon-iodine bond is achieved in most compounds by attaching it to an aromatic nucleus. An enhanced degree of solubility as well as safety is conferred on the molecule by the addition of suitable solubilizing and detoxifying groups.
Furthermore, several features are desirable for intravascular and central nervous system nonionic agents. These include (1) maximum opacity to x-ray , (2) biological safety, (3) high water solubility, (4) chemical stability, (5) low osmolality, (6) no ionic charge, and (7) low viscosity.
There is a continuing need for nonionic contrast agents which meet all or substantially all the foregoing criteria. In addition to preparing the stable, water-soluble and safe agents, the recent studies have been in the development of low osmolality agents. Studies have shown that high osmolality can be correlated with many of the undesirable physiologic adverse reactions after the x-ray contrast medium intravenous injection, e.g. nausea, vomiting, heat and pain. The most recent major improvement is the introduction of low osmolar, nonionic agents, such as iopamidol, iohexol and ioversol. These new low osmolar agents provide patient comfort by causing less nausea and vomiting on intravenous injection and much less pain on peripheral arterial injection.
SUMMARY OF THE INVENTION
Among the several objects of he invention may be noted the provision of novel nonionic contrast agents, radiological compositions and methods for x-ray visualization; and the provision of such agents which are substantially non-toxic and meet the other criteria desired for nonionic contrast agents. Other objects and features will be in part apparent and in part pointed out hereinafter.
Briefly, the present invention is directed to compounds of the formula: ##STR1## wherein the X groups may be the same or different selected from a group consisting of hydroxy and alkoxy, wherein the alkoxy group contains from 1 to 6 carbon atoms such as for example methoxy, to reduce lipophilicity.
Other compounds of the present invention are represented by the general structural formula: ##STR2## wherein the X group is selected from the group consisting of hydroxy and C.sub.1-6 alkoxy, such as for example methoxy to reduce lipophilicity; the R group s selected from the group consisting of hydrogen, --CH.sub.3 and --CH.sub.2 OH, and the R.sub.2 group is selected from the group consisting of --CH.sub.2 CH.sub.2 OH and --CH.sub.2 CH(OH)CH.sub.2 OH.
The invention is specifically directed to the compounds N-(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl-glycolamido]-N'-methyl-2,4,6- triiodoisophthalamide, N-(2,3-dihydroxypropyl) -5-[N-(2,3-dihydroxypropyl)-glycolamiclo]-N'-methyl-2,4,6-triiodoisophthal amide and N-(2,3-dihydroxypropyl) -5-[N-(2-hydroxyethyl)-2,3-dihydroxy-propionylamino]-N'-methyl-2,4,6-triio doisophthalamide . The invention is also directed to radiological compositions containing such compounds and methods for utilizing such compounds in x-ray visualization.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In accordance with the present invention, it has now been found that compounds of the formulas set out above are suitable for use as nonionic x-ray contrast agents. More specifically in the practice of the invention, the compound N-(2,3-dihydroxypropyl)-5-[-(2-hydroxyethyl)-glycolamido]-N'-methyl-2,4,6- triiodoisophthalamide may be used as a nonionic x-ray contras
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Lin Youlin
Wallace Rebecca A.
White David H.
Kumar Shailendra
Mallinckrodt Medical Inc.
Vacca Rita Downard
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