Patents by Inventor Joseph Loscalzo
Joseph Loscalzo has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 6255277Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.Type: GrantFiled: May 10, 1995Date of Patent: July 3, 2001Assignees: Brigham and Women's Hospital, NitroMed, Inc.Inventors: Jonathan Stamler, Joseph Loscalzo, John D. Folts
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Patent number: 6174539Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.Type: GrantFiled: November 4, 1999Date of Patent: January 16, 2001Assignee: Nitromed, Inc.Inventors: Jonathan Stamler, Joseph Loscalzo, John D. Folts
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Patent number: 6087479Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.Type: GrantFiled: June 2, 1995Date of Patent: July 11, 2000Assignees: NitroMed, Inc., Brigham and Women's HospitalInventors: Jonathan S. Stamler, Joseph Loscalzo, John D. Folts
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Patent number: 5863890Abstract: Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body.Type: GrantFiled: August 6, 1997Date of Patent: January 26, 1999Assignee: Brigham and Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo, Daniel Simon, David Singel
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Patent number: 5648393Abstract: Methods of relaxing corpus cavernosum smooth muscle, treating disease states responsive to prevention or relaxation of undesirable contractions of corpus cavernosum smooth muscle and of treating male impotence by administering an S-nitrosothiol such as a low molecular weight S-nitrosothiol, S-nitroso-ACE-inhibitor or S-nitroso-protein.Type: GrantFiled: August 29, 1994Date of Patent: July 15, 1997Assignee: Brigham & Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo, Adam Slivka, Daniel Simon, Robert Brown, Jeffrey Drazen
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Patent number: 5593876Abstract: Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body.Type: GrantFiled: August 9, 1994Date of Patent: January 14, 1997Assignee: Brigham and Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo, Daniel Simon, David Singel
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Patent number: 5536723Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.Type: GrantFiled: October 6, 1994Date of Patent: July 16, 1996Assignee: Brigham & Women's HospitalInventors: Joseph Loscalzo, John Cooke
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Patent number: 5459076Abstract: Nitric oxide, nitrosonium, S-nitrosothiols, and S-nitroso-proteins can be detected in biological samples, using a method which involves injection of samples into a photolysis cell, prior to detection of chemiluminescence generated by the reaction between nitric oxide and ozone. To detect S-nitrosothiols and S-nitroso-proteins separate aliquots of the same samples are subjected to pretreatment with mercurous ion, and a protein-precipitating agent, respectively, and the resulting nitric oxide signals are compared to those generated by untreated samples. This method is useful for monitoring the levels of nitric oxide bioactivity in both normal physiological states, and disease states, such as septic shock, atherosclerosis, thrombosis, hyperhomocysteinemia, pulmonary hypertension, malignancy, infections and central nervous systems disorders.Type: GrantFiled: April 22, 1992Date of Patent: October 17, 1995Assignee: Brigham and Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo
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Patent number: 5427797Abstract: Nitric oxide or nitric oxide releasing or delivering compounds administered by the inhalation route to humans and animals in need thereof have a systemic and pulmonary effect of preventing or treating blood platelet aggregation and coagulation and thus, are useful for the prevention or treatment of systemic platelet aggregation, pulmonary emboli, angina pectoris and acute respiratory distress syndrome.Type: GrantFiled: April 6, 1993Date of Patent: June 27, 1995Assignee: Brigham and Women's HospitalInventors: Claes G. Frostell, Goran Hedenstierna, Marieann E. Hogman, Joseph Loscalzo, Jonathan S. Stamler
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Patent number: 5385937Abstract: Administration of a nitrosating compound, such as nitroglycerin, nitric oxide, S-nitrosothiol, S-nitroso-protein, nitroprusside, sydnonimines, furoxans, nitrosonium salts, and related compounds is used for the treatment or prevention of disease states resulting from hyperhomocysteinemia. The disease states include vascular, ocular, skeletal, neurological, and cytotoxicity disorders. In addition, nitrosating compounds may also be administered for the treatment or prevention of disease states resulting from other sulfur-containing amino acids, such as cysteine.Type: GrantFiled: February 21, 1992Date of Patent: January 31, 1995Assignee: Brigham & Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo
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Patent number: 5380758Abstract: S-nitrosothiols exert a potent relaxant effect, mediated both by guanylate cyclase, and a cGMP-independent mechanism, upon non-vascular smooth muscle. Such types of smooth muscle include airway, gastrointestinal, bladder, uterine and corpus cavernosal. Thus, S-nitrosothiols may be used for the treatment or prevention of disorders associated with relaxation of smooth muscle, such as airway obstruction, and other respiratory disorders, bladder dysfunction, premature labor and impotence. Additionally, S-nitrosothiols may be used to alleviate smooth muscle contraction and spasm, and thus facilitate procedures involving diagnostic instrumentation, such as endoscopy, bronchoscopy, laparoscopy and cystoscopy. S-nitrosothiols also increase the binding affinity between hemoglobin and oxygen, and therefore, may be used to improve hemoglobin-oxygen binding, and oxygen transport to bodily tissues.Type: GrantFiled: September 14, 1992Date of Patent: January 10, 1995Assignee: Brigham and Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo, Adam Slivka, Daniel Simon, Robert Brown, Jeffrey Drazen
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Patent number: 5356890Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.Type: GrantFiled: February 4, 1993Date of Patent: October 18, 1994Assignee: Brigham and Women's HospitalInventors: Joseph Loscalzo, John Cooke
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Patent number: 5346599Abstract: Individual thiols present in a biological sample are separated and identified using capillary electrophoresis. S-nitrosated and oxidized derivatives of thiols are also detected using capillary electrophoresis. In addition, capillary electrophoresis may be performed on samples which have been treated with an acid, so as to achieve a pH between 2.0 and 6.8, in order to further enhance detection. Separation and detection of S-nitrosated derivatives of thiols provides a means for monitoring the extent of a disease state associated with abnormal levels of nitric oxide. Such disease states include septic shock, cardiogenic shock, hypovolemic shock, atherosclerosis, hyperhomocysteinemia, venous thrombosis, arterial thrombosis, coronary occlusion, pulmonary embolism, cerebrovascular accidents, vascular fibrosis, ectopia lentis, osteoporosis, mental retardation, skeletal deformities, pulmonary hypertension, malignancy, infections and central nervous system disorders.Type: GrantFiled: January 26, 1993Date of Patent: September 13, 1994Inventors: Jonathan Stamler, Joseph Loscalzo
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Patent number: 5298506Abstract: The invention relates to the administration of guanylate cyclase inhibitors, such as methylene blue, for the treatment of septic shock, cardiogenic shock, hypovolemic shock, obstructive shock, neuropathic shock and hypotension caused by excessive doses of nitrovasodilators. The invention also relates to the use of other redox dyes, such as toluidine blue, neutral red, tetrazolium salts, chloranil and dichlorophenolindophenol for the treatment of shock.Type: GrantFiled: May 8, 1992Date of Patent: March 29, 1994Assignee: Brigham and Women's HospitalInventors: Jonathan Stamler, Joseph Loscalzo
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Patent number: 5187183Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.Type: GrantFiled: June 14, 1991Date of Patent: February 16, 1993Assignee: Brigham & Women's HospitalInventors: Joseph Loscalzo, John Cooke
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Patent number: 5025001Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.Type: GrantFiled: March 24, 1989Date of Patent: June 18, 1991Assignee: Brigham and Women's HospitalInventors: Joseph Loscalzo, John Cooke
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Patent number: 5002964Abstract: The invention relates to novel nitroso compounds having the formula: ##STR1## wherein, R is hydroxy, NH.sub.2, NHR.sup.4, NR.sup.4 R.sup.5 or C.sub.1 -C.sub.7 alkoxy, wherein R.sup.4 and R.sup.5 are C.sub.1 -C.sub.4 alkyl, aryl, or C.sub.1 -C.sub.4 alkyl substituted by aryl;R.sup.1 is hydrogen, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.7 alkyl substituted by phenyl, amino, guanidino, NHR.sup.6 or NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 are methyl, or C.sub.1 -C.sub.4 acyl;R.sup.3 is hydrogen, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.7 alkyl substituted by phenyl;n is 0 to 2;A is hydrogen,lower C.sub.1 -C.sub.7 alkyl,lower C.sub.2 -C.sub.7 alkylene,lower C.sub.2 -C.sub.7 alkylene substituted by hydroxy, C.sub.1 -C.sub.4 alkyl, aryl, ora C.sub.4 -C.sub.7 ring which may be fused to a benzene ring;B is hyrogen,lower C.sub.1 -C.sub.7 alkyl,phenyl,lower C.sub.1 -C.sub.7 substituted by phenyl, hydroxy, guanidino, amino, imidazoyl, indolyl, mercapto, mercapto substituted by lower C.sub.1 -C.sub.Type: GrantFiled: June 15, 1988Date of Patent: March 26, 1991Assignee: Brigham & Women's HospitalInventor: Joseph Loscalzo