Nitrosamines (i.e., Compounds Containing Nitroso Bonded Directly To Amino Nitrogen) Patents (Class 514/611)
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Patent number: 10662063Abstract: The invention proposes the photosensitized generation of nitric oxide (NO) from alanosine (3-(hydroxynitrosoamino)-D,L-alanine) by aluminum phthalocyanine tetrasulfonate (AlPcS4). While NO is obtained in nitrogen-saturated solutions, the invention proposes that both NO and peroxynitrite are produced in air-saturated solutions. Enhancement of NO production occurs in the presence of ubiquinone-0. The invention evidence that NO is produced by the photosensitized oxidation of alanosine. Both NO and peroxynitrite are detected during photoirradiation of AlPcS4 in the presence of 2-methyl-2-nitrosopropane (MNP) and hypoxanthine, but not in the absence of hypoxanthine, in air-saturated solutions, where HX is acting as sacrificial electron donor, thus promoting superoxide formation.Type: GrantFiled: June 6, 2017Date of Patent: May 26, 2020Assignee: University of Puerto RicoInventors: Antonio E. Alegria, Pedro Sanchez Cruz
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Patent number: 8853282Abstract: A topical liquid formulation is provided which contains a combination of three active ingredients for treating fleas and ticks in domestic animals. Total concentration of the active hydrophobic and hydrophilic ingredients can exceed 60 weight percent. In contrast to commonly available flea treatments, the new insecticidal composition is safe and effective for both felines and canines and a single topical application can be effective for at least several weeks.Type: GrantFiled: May 22, 2014Date of Patent: October 7, 2014Assignee: Sumitomo CorporationInventor: Ian Cottrell
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Publication number: 20140088034Abstract: The invention provides methods of treating nitric oxide/cGMP pathway-cell adhesion disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention relates to a method for down-regulating ?4?1-integrin affinity and inhibiting and reversing adhesion formation in patients or subjects in need using a nitric oxide donor.Type: ApplicationFiled: May 10, 2012Publication date: March 27, 2014Inventors: Alexandre Chigaev, Larry A. Sklar
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Publication number: 20140057001Abstract: Provided herein are methods of using gaseous nitric oxide and/or at least one nitric oxide source to or decrease sebum production in the skin of a subject.Type: ApplicationFiled: October 31, 2013Publication date: February 27, 2014Applicant: Novan, Inc.Inventors: Susanne Bauman, Nathan Stasko
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Publication number: 20130315981Abstract: The present invention is a method of increasing lipolysis in an adipose tissue of a mammal comprising delivering to macrophages at the adipose tissue of the mammal an effective amount of an agent which reduces the concentration of macrophages at the adipose tissue of the mammal, thereby increasing lipolysis in the adipose tissue of the mammal.Type: ApplicationFiled: June 22, 2011Publication date: November 28, 2013Applicant: The Trustees of Columbia University in the City of New YorkInventors: Anthony W. Ferrante, JR., Aliki Kosteli
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Publication number: 20130195926Abstract: The instant invention provides methods for treating a solid tumor in a subject comprising modulating nitric oxide production in the tumor to normalize tumor vasculature and administering an anti-tumor therapy to the subject. The invention further provides methods of treating a solid tumor in a subject comprising selectively increasing cyclic guanosine monophosphate (cGMP) or cGMP dependent protein kinase G production in the tumor vasculature to an amount effective to normalize tumor vasculature and administering an anti-tumor therapy to the subject.Type: ApplicationFiled: December 4, 2012Publication date: August 1, 2013Applicant: The General Hospital CorporationInventor: The General Hospital Corporation
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Publication number: 20120064180Abstract: The present invention relates to a method for terminating dormancy in an invertebrate, wherein said invertebrate is brought in contact with nitric oxide and/or a nitric oxide donor. The method can be used in pest management of unfavourable species, in eliminating dormant stages of aquatic invertebrates in ballast water in promoting termination of dormancy in beneficial species and/or in stimulating production of live food in aquacultures.Type: ApplicationFiled: May 12, 2010Publication date: March 15, 2012Applicant: UNIVERSITEIT GENTInventors: Peter Bossier, Guy Smagghe
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Publication number: 20120058058Abstract: The present invention relates to novel compounds and compositions and the use of them for the control of fungal and bacterial pathogens, insect pests, acari, nematodes and other invertebrate pests including, but not limited to post-harvest and soil diseases, building mold remediation, and seed and grain sanitation.Type: ApplicationFiled: May 11, 2010Publication date: March 8, 2012Applicant: AGRAQUEST, INC.Inventors: Jorge I. Jimenez, Jonathan S. Margolis, John Kenneth Baird, Sarah F. Lego
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Publication number: 20120021055Abstract: The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.Type: ApplicationFiled: June 24, 2011Publication date: January 26, 2012Applicant: The University of North Carolina at Chapel HillInventors: Mark H. Schoenfisch, Jae Ho Shin, Nathan Stasko
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Publication number: 20110300232Abstract: Nitric Oxide (NO) acts as double-edged sword, which induces and prevents cell death, depending on various factors. The mechanism for the NO regulation of cells is not fully understood. The present invention provides experiment design methods and therapy design methods leveraging viable hypothesis supported by current research findings. This invention determines the effects of NO by controlling the majority parameters such as the steady-state concentration of NO, duration of NO exposure and the local level of oxygen. The experiment designs are structured to improve understanding of NO regulation of cells, and further can be directly adapted for therapy design. The invention directs these experiment design and therapy design methods to the study and treatment of cancer. In an application, the effects of exogenous NO on inducible Nitric Oxide Synthase (iNOS) expression and signal transduction in ovarian cancer is applied to drug discovery and therapy design for ovarian and other cancers.Type: ApplicationFiled: June 7, 2011Publication date: December 8, 2011Inventor: Pooncharas Tipgunlakant
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Publication number: 20110293556Abstract: This invention relates to Applicant's discovery that Metabolic Syndrome , a cluster of disorders stemming from a resistance to insulin, contributes directly to dementia, particularly Alzheimer's disease. Applicant's invention includes a screening method to determine susceptibility and diagnosis of dementia based on the risk factors for Metabolic Syndrome. Applicant's invention further includes methods for the prevention or treatment of dementia and other neurological conditions based on (1) minimizing insulin resistance, thereby preventing excess biosynthesis of insulin; (2) modulating the activity of IDE such that insulin competes less efficiently with ?-amyloid protein for the TDE; and (3) blocking the consequences of NMDA receptor activation, such as by minimizing the generation of NO and other harmful free radicals.Type: ApplicationFiled: August 8, 2011Publication date: December 1, 2011Applicant: SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTEInventors: Stuart A. LIPTON, Daniel EINHORN
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Patent number: 8062656Abstract: The invention provides NO-releasing polymers and low molecular weight NO-releasing compounds which may be used to for the treatment of medical conditions associated with NO-deficiency. The NO-releasing polymers or the low molecular weight NO-releasing compounds may also be incorporated into medical devices. The invention further provides methods of controlled release of NO for the treatment of diseases and disorders associated with NO-deficiency, wherein the treatment includes systemic or local administration of the NO-releasing polymers or the low molecular weight NO-releasing compounds.Type: GrantFiled: April 18, 2008Date of Patent: November 22, 2011Assignee: Central Michigan UniversityInventors: Justin D. Oh-Lee, Dillip K. Mohanty
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Publication number: 20110081427Abstract: Administration of an HNO/NO? donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO? donating compound isopropylamine (IPA)/NO (Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO? donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO? donors, administration of an HNO/NO? donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO? exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.Type: ApplicationFiled: November 18, 2010Publication date: April 7, 2011Applicants: The Government of the U.S.A. as represented by the Secretary of the Dept. of Health and Human Servic, The Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, The Regents of the University of California, Johns Hopkins UniversityInventors: David A. Wink, Martin Feelisch, David A. Kass, Nazareno Paolocci, Katrina Miranda, Jon Fukuto, Tatsuo Katori
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Patent number: 7902225Abstract: The present invention relates to novel substituted quinoline derivatives according to the general Formula (Ia) or the general Formula (Ib) the pharmaceutically acceptable acid or base addition salts thereof, the quaternary amines thereof, the stereochemically isomeric forms thereof the tautomeric forms thereof and the N-oxide forms thereof. The claimed compounds are useful for the treatment of mycobacterial diseases. In particular, compounds are claimed in which, independently from each other, R1 is halo; p=1; R2 is optionally substituted alkyloxy, alkyl, Ar, Het, or a radical of formula R3 is optionally substituted Ar or Het; q=1, R4 and R5 each independently are alkyl; R6 is hydrogen or a radical of formula r is equal to 0 or 1 and R7 is hydrogen or Ar.Type: GrantFiled: January 21, 2005Date of Patent: March 8, 2011Assignee: Janssen Pharmaceutica NVInventors: Jérôme Emile Georges Guillemont, Elisabeth Therese Jeanne Pasquier, David Francis Alain Lancois
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Patent number: 7863262Abstract: Administration of an HNO/NO? donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO? donating compound isopropylamine (IPA)/NO(Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO? donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO? donors, administration of an HNO/NO? donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO? exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.Type: GrantFiled: March 31, 2005Date of Patent: January 4, 2011Assignees: Johns Hopkins University, The United States of America as represented by the Department of Health and Human Services, The Regents of the University of California, The Board of Supervisors of Louisiana State University and Agriculture and Mechanical CollegeInventors: David A. Wink, Martin Feelisch, David A. Kass, Nazareno Paolocci, Katrina Miranda, Jon Fukuto, Tatsuo Katori
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Publication number: 20100098733Abstract: The present invention provides an oral care composition Comprising a nitric oxide releasing particle and an orally-acceptable carrier. The nitric oxide releasing particle comprises at least one nitric oxide donor. Another aspect of the present invention provides a device for oral care comprising a nitric oxide releasing particle, wherein the device is configured to expose a targeted site in an oral cavity of a subject to nitric oxide. The present invention also provides methods and uses of providing oral health benefits by using the oral care compositions or devices as described above.Type: ApplicationFiled: October 16, 2009Publication date: April 22, 2010Inventor: Nathan Stasko
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Patent number: 7696247Abstract: Novel nitric-oxide releasing lipid molecules are provided which comprise a lipid molecule selected from (a) phosphoglycerides, (b) lipids having a sphingosine base as a backbone, (c) monoacylglyerols, (d) diacylglycerols, (e) glycosylacylglycerols, and (f) sterol compounds of the formula: where R is a branched aliphatic chain of eight or more carbon atoms, wherein the lipid molecule is provided with a nitric-oxide containing group which comprises (a) a —S—N?O moiety, (b) a —O—N?O moiety, or (c) a a moiety. Also provided are methods of forming such nitric oxide releasing lipid molecules. Various pharmaceutical compositions, topical liquids and drug delivery systems comprising the nitric-oxide releasing lipid molecules are also described.Type: GrantFiled: July 6, 2004Date of Patent: April 13, 2010Assignee: Boston Scientific Scimed, Inc.Inventors: Robert A. Herrmann, Wendy Naimark
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Patent number: 7572798Abstract: The present invention relates to a series of new chemical agents that demonstrate anti-tumor activity. More particularly, the present invention relates to molecules, referred to as “combi-molecules”, that combine two major mechanisms of anti-tumor action. A combi-molecule is capable of degrading to a ligand involved in cell signaling pathways and to an agent capable of damaging DNA. More specifically, the present invention relates to molecules capable of blocking epidermal growth factor receptor (EGFR) mediated signal transduction and capable of damaging DNA. The present invention also relates to a general method of synthesis of these combi-molecules.Type: GrantFiled: February 26, 2002Date of Patent: August 11, 2009Assignee: McGill UniversityInventors: Bertrand J. Jean-Claude, Fabienne Dudouit, Stephanie Matheson
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Publication number: 20090118660Abstract: Method for in-vivo plasmapheresis utilizing a plurality of elongated hollow microporous filter fibers periodically interrupt diffusion of blood plasma from a patient, and, for a selected time, directing backflush fluid into the fibers at a pressure and interval sufficient to cleanse the fiber pores, after which plasma diffusion is resumed. The backflush fluid, preferably a normal saline solution, may contain an anticoagulant such as heparin, citrate or NO donor in suitable concentration for systemic anti-coagulation or for treating the fiber for thromboresistance.Type: ApplicationFiled: January 13, 2009Publication date: May 7, 2009Applicant: Transvivo Inc.Inventors: Reynolds G. Gorsuch, Tommy Gene Cooper, Harold H. Handley, JR., Harold W. Peters
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Publication number: 20090041869Abstract: The present invention discloses Resistance Management (RM) practices that are critical to safeguard Bacillus thuringiensis as a natural resource and sustain genetically modified corn expressing Bt toxins as a suitable method for ECB and WCRW management. A useful tool in developing RM strategies is to develop laboratory selected colonies that exhibit high levels of resistance to a particular toxin. The availability of selected strains allows determination of the genetic expression of resistance (i.e., dominant vs. recessive, autosomal vs. sex-linked) and whether or not the resistance mechanism is specific for a given toxin. In addition, the availability of resistant strains will allow estimation of the particular resistance allele frequency in the field, and provides a tool to identify the biochemical and physiological basis of resistance and a means to develop molecular probes to monitor the evolution of resistance in the field.Type: ApplicationFiled: October 15, 2008Publication date: February 12, 2009Applicant: PIONEER HI-BRED INTERNATIONAL, INC.Inventor: DANIEL J. COSGROVE
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Publication number: 20080300313Abstract: The present invention relates to a solvent mixture SM for preparing a water-dilutable liquid concentrate formulation of sparingly soluble organic pesticide compounds C having a water solubilty of not more than 5 g/l at 25° C./1013 mbar. The present invention also relates to water-dilutable liquid concentrate formulation, which comprises said solvent mixture SM and at least one non-ionic surfactant.Type: ApplicationFiled: January 4, 2007Publication date: December 4, 2008Inventors: Thomas Byrne, Charles W. Finch
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Publication number: 20080286321Abstract: The present invention relates to nanofibers that produce therapeutic amounts of nitric oxide after a delay period, which allows time to install or implant the device into a patient. The nitric oxide release is thus localized to the area of the organism where NO dosing is indicated. The delay time is achieved by cospinning the NO-producing fiber with a fiber that tends to sequester the former's NO-producing functional groups. Fibers of the present invention may be incorporated into medical devices such as stents or other implantable medical devices to prevent the formation of adhesions or scarring in the area of the implant.Type: ApplicationFiled: January 24, 2005Publication date: November 20, 2008Inventors: Darrell Reneker, Daniel J. Smith
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Publication number: 20080260797Abstract: The invention provides NO-releasing polymers and low molecular weight NO-releasing compounds which may be used to for the treatment of medical conditions associated with NO-deficiency. The NO-releasing polymers or the low molecular weight NO-releasing compounds may also be incorporated into medical devices. The invention further provides methods of controlled release of NO for the treatment of diseases and disorders associated with NO-deficiency, wherein the treatment includes systemic or local administration of the NO-releasing polymers or the low molecular weight NO-releasing compounds.Type: ApplicationFiled: April 18, 2008Publication date: October 23, 2008Inventors: Justin D. Oh-Lee, Dillip K. Mohanty
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Publication number: 20080226753Abstract: The present invention discloses Resistance Management (RM) practices that are critical to safeguarding Bacillus thuringiensis as a natural resource and to sustaining genetically modified crops that express Bt toxins for managing ECB and WCRW. The methods involve blending seed transformed with a nucleic acid encoding a different pesticidal protein, where both proteins target the same pest, but use different modes of pesticidal action. The seed can be also treated with pesticidal agents.Type: ApplicationFiled: March 29, 2005Publication date: September 18, 2008Applicant: PIONEER HI-BRED INTERNATIONAL, INC.Inventor: Daniel J. Cosgrove
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Publication number: 20080214646Abstract: This invention provides a prodrug that help arthritis patients without increasing cardiovascular and gastrointestinal risk. A novel group of hybrid nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs), moiety attached via a one -carbon methylene spacer to the carboxylic acid group of the traditional NSAIDs aspirin, ibuprofen and indomethacin were synthesized. The ester prodrugs showed equipotent anti-inflammatory activities in vivo to that of the parent aspirin, ibuprofen and indomethacin. The simultaneous release of parent drug and nitric oxide from the NO- prodrugs constitutes a potentially beneficial property for the prophylactic prevention of thrombus formation and adverse cardiovascular events such as stroke and myocardial infarction. Data acquired in an in vivo ulcer index (UI) assay showed that this group of ester prodrugs in which no lesions were observed when compared to the parent drugs at equivalent doses.Type: ApplicationFiled: May 16, 2006Publication date: September 4, 2008Inventors: Edward E. Knaus, Carlos Velazquez
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Patent number: 7135498Abstract: There is provided a method of promoting neurogenesis by administering a therapeutic amount of a nitric oxide donor compound to a patient in need of neurogenesis promotion. Also provided is a compound for providing neurogenesis having an effective amount of a nitric oxide donor sufficient to promote neurogenesis. A nitric oxide compound for promoting neurogenesis is also provided. Further, a method of augmenting the production of brain cells and facilitating cellular structural and receptor changes by administering an effective amount of a nitric oxide donor compound to a site in need of augmentation is provided. There is provided method of increasing both neurological and cognitive function by administering an effective amount of a nitric oxide donor compound to a patient.Type: GrantFiled: June 14, 2000Date of Patent: November 14, 2006Assignee: Henry Ford Health SystemInventors: Michael Chopp, Rui Lan Zhang
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Patent number: 6984624Abstract: The invention concerns a pharmaceutical composition or a food supplement containing at least an iron complexing protein optionally in the presence of at least an iron salt, and at least a precursor of nitrogen monoxide metabolism and/or at least a chemical donor of nitrogen monoxide, the use of at least an iron complexing agent and of at least a precursor of nitrogen monoxide metabolism and/or a chemical donor of nitrogen monoxide, and optionally at least an iron salt for making pharmaceutical compositions in particular for treating asthenia or anaemia or for making a food supplement.Type: GrantFiled: July 27, 2001Date of Patent: January 10, 2006Assignee: Isocell S.A.Inventor: Bernard Dugas
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Patent number: 6936639Abstract: Administration of an HNO/NO? donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure Moreover, administration of the HNO/NO? donating compound isopropylamine (IPA)/NO (Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO? donating compound Angeli's salt.Type: GrantFiled: August 21, 2002Date of Patent: August 30, 2005Assignees: The United States of America as represented by the Secretary of the Department of Health and Human Services, The Regents of the University of California, Johns Hopkins University, The Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, Louisiana State University Health Sciences CenterInventors: David A. Wink, Martin Feelisch, David A. Kass, Nazareno Paolocci, Katrina Miranda, Jon Fukuto, Tatsuo Katori
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Patent number: 6911478Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.Type: GrantFiled: March 23, 2004Date of Patent: June 28, 2005Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Joseph A. Hrabie, Larry K. Keefer
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Patent number: 6872751Abstract: The present invention relates to methods for prevention and/or treatment of diseases or conditions caused by deficiency in the adult isoform of a given protein wherein said method comprises administering to a patient in need thereof a composition containing NO or at least one compound able to release, induce and/or promote NO formation in cells, said administration resulting in augmenting or restoring the production of the fetal isoform of said protein in said patient.Type: GrantFiled: April 29, 2002Date of Patent: March 29, 2005Assignee: Centre National de la Recherche Scientifique - CNRSInventors: Maurice Israël, Sabine De La Porte, Philippe Fossier, Emmanuel Chaubourt, Gérard Baux, Christiane Leprince
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Patent number: 6780849Abstract: Novel nitric-oxide releasing lipid molecules are provided which comprise a lipid molecule selected from (a) phosphoglycerides, (b) lipids having a sphingosine base as a backbone, (c) monoacylglyerols, (d) diacylglycerols, (e) glycosylacylglycerols, wherein the lipid molecole is provided with a nitric-oxide contianing group which comprises a (a) a —S—N═O moiety, (b) a —O—N═O moiety, or (c) a moiety. Also provided are methods of forming such nitric oxide releasing lipid molecules. Various pharmaceutical compositions, topical liquids and drug delivery systems comprising the ntric-oxide releasing lipid molecules are also described. Further provided are methods for therapeutically administering nitric oxide to patients, methods for treating or preventing various conditions, methods for promoting wound healing and methods for reducing the cells present in an atherosclerotic lesion which methods utilize the nitric-oxide releasing lipid molecules.Type: GrantFiled: December 21, 2000Date of Patent: August 24, 2004Assignee: SciMed Life Systems, Inc.Inventors: Robert A. Herrmann, Wendy Naimark
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Patent number: 6750254Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.Type: GrantFiled: January 22, 2003Date of Patent: June 15, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Joseph A. Hrabie, Larry K. Keefer
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Publication number: 20040039063Abstract: Administration of an HNO/NO− donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure Moreover, administration of the HNO/NO− donating compound isopropylamine (IPA)/NO (Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO− donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO− donors, administration of an HNO/NO− donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent Further, HNO/NO− exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.Type: ApplicationFiled: August 21, 2002Publication date: February 26, 2004Applicants: Department of Health and Human Services, National Institutes of HealthInventors: David A. Wink, Martin Feelisch, David A. Kass, Nazareno Paolocci, Katrina Miranda, Jon Fukuto, Tatsuo Katori
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Patent number: 6656452Abstract: A method for lessening or preventing non-pulmonary ischemia-reperfusion injury or inflammation in a mammal by identifying a mammal which has ischemia-reperfusion or is at risk for developing ischemia-reperfusion in a non-pulmonary tissue; and causing the mammal to inhale a therapeutically effective amount of gaseous nitric oxide sufficient to diminish the ability of leukocytes or platelets to become activated in a manner that contributes to an inflammatory process at the site of the ischemia-reperfusion or inflammation in the non-pulmonary tissue, thereby lessening or preventing non-pulmonary ischemia-reperfusion injury in the mammal.Type: GrantFiled: November 14, 1997Date of Patent: December 2, 2003Assignee: The General Hospital CorporationInventors: Warren M. Zapol, Kenneth D. Bloch
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Patent number: 6511991Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine and enamine derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.Type: GrantFiled: April 3, 2001Date of Patent: January 28, 2003Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Joseph A. Hrabie, Larry K. Keefer
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Patent number: 6482846Abstract: Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.Type: GrantFiled: August 30, 2001Date of Patent: November 19, 2002Assignee: NitroMed, Inc.Inventors: David S. Garvey, L. Gordon Letts, H. Burt Renfroe, Sang William Tam
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Patent number: 6472390Abstract: Patients with pathologic conditions involving constriction or proliferation of smooth muscle or disease associated with cysteine containing proteins, or who are at risk for such, are administered a therapeutically effective amount of a nitric oxide (NO) donor which is insufficient to acutely lower mean arterial blood pressure or pulmonary artery pressure by more than 10%. In one subgenus, NO donor is administered to modify red blood cell membrane receptors to prevent red blood cells from causing vasoconstriction. A related method which allows increased dosage of NO donor without acutely lowering mean arterial blood pressure comprises administering the NO donor into an artery of the patient. In another method, patients having a cardiovascular syndrome, or who are at risk for such, are administered a therapeutically effective amount of thiol which does not acutely affect blood pressure to a significant degree.Type: GrantFiled: November 13, 2001Date of Patent: October 29, 2002Assignee: Duke UniversityInventors: Jonathan S. Stamler, Claude A. Piantadosi, Mark W. Dewhirst
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Patent number: 6379660Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N2O2− functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.Type: GrantFiled: September 20, 2000Date of Patent: April 30, 2002Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Joseph E. Saavedra, Larry K. Keefer, Peter P. Roller, Miki Akamatsu
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Patent number: 6323234Abstract: Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; composition comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.Type: GrantFiled: March 3, 2000Date of Patent: November 27, 2001Assignee: NitroMed, Inc.Inventors: David S. Garvey, L. Gordon Letts, H. Burt Renfroe, Sang William Tam
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Patent number: 6287601Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.Type: GrantFiled: June 16, 1999Date of Patent: September 11, 2001Inventor: Meri Charmyne Russell
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Patent number: 6200558Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N2O2− functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.Type: GrantFiled: April 22, 1997Date of Patent: March 13, 2001Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Joseph E. Saavedra, Larry K. Keefer, Peter P. Roller, Miki Akamatsu
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Patent number: 6190704Abstract: The present invention provides methods and compositions for promoting healing of damaged tissue that result in an increased level of nitric oxide in the vicinity of the damaged tissues. Also provided are methods and compositions for inhibiting unwanted wound healing by inhibiting the activity of nitric oxide in the tissue.Type: GrantFiled: September 23, 1994Date of Patent: February 20, 2001Assignee: New York Society for the Ruptured and Crippled Maintaining the Hospital for Special SurgeryInventor: George Anthony Calvert Murrell
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Patent number: 6147068Abstract: A pharmaceutical composition of matter for delivering nitric oxide. The composition is an amine that was reacted with nitric oxide. The composition of matter is lipophilic and insoluble and therefore delivers nitric oxide to the specific area of the body where it is introduced. Also, a method of synthesizing an amine and reacting it with nitric oxide to form the pharmaceutical composition of matter. Finally, a method of using the pharmaceutical composition of matter to deliver nitric oxide to the body.Type: GrantFiled: September 21, 1998Date of Patent: November 14, 2000Assignee: The University of AkronInventors: Daniel J. Smith, Dominick Roselle
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Patent number: 6121321Abstract: Substituted methoxy benzylidene indenyl compounds are useful in the treatment of precancerous lesions and neoplasms.Type: GrantFiled: June 13, 1996Date of Patent: September 19, 2000Assignees: Cell Pathways, Inc., University of ArizonaInventors: Gerhard Sperl, Paul Gross, Klaus Brendel, Gary A. Piazza, Rifat Pamukcu
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Patent number: 6057347Abstract: Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.Type: GrantFiled: September 16, 1997Date of Patent: May 2, 2000Assignee: NitroMed, Inc.Inventors: David S. Garvey, L. Gordon Letts, H. Burt Renfroe, Sang William Tam
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Patent number: 6045827Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.Type: GrantFiled: August 19, 1997Date of Patent: April 4, 2000Assignee: Meri Charmyne RussellInventor: Meri Charmyne Russell
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Patent number: 5958427Abstract: The invention is directed to nitric oxide (NO) donor compounds and to pharmaceutical compositions containing such nitric oxide (NO) donor compounds, for delivering NO to the apical surface of a mucosa, where the nitric oxide is released for passage across the epithelial monolayer of the mucous membrane. The NO donor compounds include polyalkyleneamine NO donors as well as tertiary and quaternary amino aliphatic NO donor compounds. The compounds and compositions of the invention are useful in any situation in which it is desirable to deliver NO across a mucosal surface. For example, the compounds and compositions of the invention are particularly useful in treating pulmonary hypertension, male impotence, and several other specific conditions.Type: GrantFiled: November 8, 1996Date of Patent: September 28, 1999Inventors: Andrew L. Salzman, Daniel J. Smith, Csaba Szabo, Richard J. Brilli, Brian Krafte-Jacobs
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Patent number: 5905086Abstract: N-(2-Hydroxyethyl)nicotinamide nitrate or its salt prevents or ameliorates anxiety neurosis or panic disorder, or the following anxiety. This compound or its salt has few side effects and exhibits immediate action.Type: GrantFiled: February 13, 1998Date of Patent: May 18, 1999Assignee: Chugai Seiyaku Kabushiki KaishaInventor: Toshiro Miura
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Patent number: 5840759Abstract: The present invention provides a method for sensitizing hypoxic cells in a tumor to radiation, wherein nitric oxide is delivered to target hypoxic cells through the administration of a nitric oxide-containing compound that spontaneously releases nitric oxide under physiological conditions without requiring the presence of oxygen. Also provided are methods of protecting noncancerous cells or tissues in a mammal from radiation, sensitizing cancerous cells in a mammal to chemotherapeutic agents, and protecting noncancerous cells or tissues in a mammal from chemotherapeutic agents, all by administration of the same compounds.Type: GrantFiled: March 11, 1997Date of Patent: November 24, 1998Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: James B. Mitchell, Angelo Russo, Murali C. Krishna, David A. Wink, Jr., James E. Liebmann
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Patent number: 5837736Abstract: The present invention provides a method for sensitizing hypoxic cells in a tumor to radiation, wherein nitric oxide is delivered to target hypoxic cells through the administration of a nitric oxide-containing compound that spontaneously releases nitric oxide under physiological conditions without requiring the presence of oxygen. Also provided are methods of protecting noncancerous cells or tissues in a mammal from radiation, sensitizing cancerous cells in a mammal to chemotherapeutic agents, and protecting noncancerous cells or tissues in a mammal from chemotherapeutic agents, all by administration of the same compounds.Type: GrantFiled: March 11, 1997Date of Patent: November 17, 1998Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: James B. Mitchell, Angelo Russo, Murali C. Krishna, David A. Wink, Jr., James E. Liebmann