Invivo agents comprising cationic metal chelators with acidic saccharides and glycosaminoglycans
AssigneeAccess Pharmaceuticals, Inc.
InventorDavid F. Ranney
Life of this patent
Estimating the term…
Loading patent…
AssigneeAccess Pharmaceuticals, Inc.
InventorDavid F. Ranney
Estimating the term…
This application concerns novel agents comprising cationic or chemically basic metal chelators in association with hydrophilic carriers of anionic or chemically acidic saccharides, sulfatoids and glycosaminoglycans. In certain embodiments, the agents comprise metals and metal ions. Covalent and non-covalent chemical and physical means are described for stabilizing the binding of the metal chelators to the carriers. Novel non-covalently bound compositions are described which give uniquely high payloads and ratio of metal chelator to carrier, ranging from a low of about 15% metal chelator by weight, to a characteristic range of 70% to 90% metal chelator by weight. Specific embodiments are described comprising deferoxamine, ferrioxamine, iron-basic porphine, iron-triethylenetetraamine, gadolinium DTPA-lysine, gadolinium DOTA-lysine and gadolinium with basic derivatives of porphyrins, porphines, expanded porphyrins, Texaphyrins and sapphyrins as the basic or cationic metal chelators, which are in turn, bound to acidic or anionic carriers, including one or more of acidic or anionic saccharides, and including sulfated sucrose, pentosan polysulfate, dermatan sulfate, oversulfated dermatan sulfate, chondroitin sulfate, oversulfated chondroitin sulfate, heparan sulfate, beef heparin, porcine heparin, non-anticoagulant heparins, and other native and modified acidic saccharides and glycosaminoglycans. Also disclosed are methods of enhancing in vivo imgages arising from induced magnetic resonance signals, methods of enhancing in vivo images in conjunction with ultrasound or X-rays and methods of obtaining in vivo body images utilizing radioisotope containing agents. Methods of treating vasular disease are also disclosed.
An agent comprising at least about 15 weight percent chelator for paramagnetic metal ions, and a sulfated oligosaccharide, sulfated polysaccharide or glycosaminoglycan carrier, said chelator having a cationic group and being bound to said carrier by non-covalent binding.
An agent for magnetic resonance imaging comprising deferoxamine non-covalently bound to a carrier selected from the group consisting of heparin, heparan sulfate, dermatan sulfate and chondroitin sulfate.
An agent for in vivo magnetic resonance imaging, the agent comprising a chelator having a net positive charge at physiological pH, a chelated metal ion and a sulfated hydrophilic carrier, said chelator/metal ion chelate being bound by non-covalent binding at a weight percentage of at least about 15% to said carrier, and said carrier being selected from the group consisting of heparin, desulfated heparin, glycine-conjugated heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate, pentosan polysulfate and dextran sulfate.
An agent for enhancing body imaging, the agent comprising diethylenetriaminepentaacetate-lysine, chelated Gd(III) and a glycosaminoglycan carrier non-covalently bound to said diethylenetriaminepentaacetate-lysine.
An agent for enhancing body imaging, the agent comprising DOTA-lysine, chelated Gd(III) and a glycosaminoglycan carrier non-covalently bound to said 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetate-lysine (DOTA-lysine).
An agent for magnetic resonance imaging comprising ferrioxamine bound by non-covalent binding to dermatan sulfate.
Dependencies are inferred from the claim text.