Abstract: Compounds that demonstrate chelation affinity and selectivity for first transition series elements are administered to patients suffering from such conditions as ischemia, prolonged seizures and trauma to provide neuroprotection, cardioprotection, or both. These compounds when administered form complexes with chelatable iron and copper cations and thereby mitigate the ability of these cations to catalyze Haber-Weiss reactions that form toxic hydroxy free radicals that cause tissue injury. These compounds also form complexes with chelatable zinc cations thereby inhibiting the cytotoxicity associated with excess chelatable zinc.
Abstract: Compounds that demonstrate chelation affinity and selectivity for first transition series elements are administered to patients suffering from such conditions as ischemia, prolonged seizures and trauma to provide neuroprotection, cardioprotection, or both. These compounds when administered form complexes with chelatable iron and copper cations and thereby mitigate the ability of these cations to catalyze Haber-Weiss reactions that form toxic hydroxy free radicals that cause tissue injury. These compounds also form complexes with chelatable zinc cations thereby inhibiting the cytotoxicity associated with excess chelatable zinc.
Type:
Application
Filed:
June 13, 2002
Publication date:
January 8, 2004
Applicants:
CONCAT, LTD. a California Limited Partnership, CHELATOR LLC., a Delaware corporation
Abstract: This invention involves synthesis and use of a class of compounds with chelation affinity and selectivity for first transition series elements. Administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease in the in vivo bioavailability of first transition series elements and/or removal from the body of first transition series elements and elements with similar chemical properties. These characteristics make such compounds useful in the management of diseases associated with a bodily excess of first transition series elements and elements with similar chemical properties. This invention demonstrates that such compounds inhibit mammalian, bacterial, and fungal cell replication and are therefore useful in the treatment of neoplasia, infection, inflammation, immune reponse, and in termination of pregnancy.
Type:
Grant
Filed:
September 19, 2000
Date of Patent:
October 22, 2002
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
Abstract: This invention involves the use of a class of compounds with chelation affinity and selectivity for first transition series elements. Application or administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease of the bioavailability and/or chemical action of first transition series elements. These characteristics make such compounds useful in cosmetics and personal care products to decrease odor arising from microbial growth on body surfaces and in body cavities, decrease microbial growth on teeth, plaque, and gums that cause tooth decay and gum disease, inhibition of oxidative damage to the skin, inhibition of enzymatic action of metalloenzymes dependent on first transition series elements, and inhibition of reperfusion injury.
Type:
Grant
Filed:
April 20, 2001
Date of Patent:
May 14, 2002
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
Abstract: This invention involves the use of a class of compounds with chelation affinity and selectivity for first transition series elements. Application or administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease of the bioavailability and/or chemical action of first transition series elements. These characteristics make such compounds useful in cosmetics and personal care products to decrease odor arising from microbial growth on body surfaces and in body cavities, decrease microbial growth on teeth, plaque, and gums that cause tooth decay and gum disease, inhibition of oxidative damage to the skin, inhibition of enzymatic action of metalloenzymes dependent on first transition series elements, and inhibition of reperfusion injury.
Type:
Grant
Filed:
February 22, 2000
Date of Patent:
July 24, 2001
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.
Type:
Grant
Filed:
May 30, 1995
Date of Patent:
January 14, 1997
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
Abstract: Ligands with three or more nitrogen atoms incorporated into a linear or cyclic backbone structure, with the nitrogen atoms substituted with a combination of phosphonate groups and nonphosphonate groups, of which at least two are phosphonate groups, are disclosed. These ligands are combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups linked to the backbone nitrogens are preferred.
Type:
Grant
Filed:
August 13, 1993
Date of Patent:
April 25, 1995
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Rosa L. Cyjon, Eliot D. Simhon
Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.
Type:
Grant
Filed:
July 22, 1993
Date of Patent:
January 10, 1995
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.
Type:
Grant
Filed:
September 11, 1991
Date of Patent:
August 17, 1993
Assignee:
Concat, Ltd.
Inventors:
Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad