186 results about "Endothelial dysfunction" patented technology

The present invention concerns methods for treating and preventing renal / kidney disease, insulin resistance / diabetes, fatty liver disease, and / or endothelial dysfunction / cardiovascular disease using synthetic triterpenoids, optionally in combination with a second treatment or prophylaxis.

The present invention is directed to a method of simultaneously treating hypertension, hypertriglyceridemia, a pro-inflammatory state, a pro-coagulative state, and insulin resistance (with or without treating obesity or endothelial dysfunction), associated with or independent from Metabolic Syndrome, as well as vascular disease such as cardiovascular, cerebrovascular, or peripheral vascular disease comprising the step of administering to a patient suffering from such disorders a therapeutically effective amount of a central acting dopamine agonist. In one embodiment, the central acting dopamine agonist is bromocriptine, optionally combined with a pharmaceutically acceptable carrier.

A compound having the structureuseful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina pectoris, thromboses, restenoses, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver in a human or animal patient.

A compound having the structureuseful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina pectoris, thromboses, restenoses, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver in a human or animal patient.

This inventions relates to compounds having the structure Formula Iand pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Compounds comprising nitric oxide derivatives of stilbenes, polyphenols and flavonoids and methods of their use are provided for treating patients suffering from any of hypercholesterolemia, vascular oxidative stress and endothelial dysfunction.

A method and apparatus for non-invasively evaluating endothelial activity in a patient, particularly for indicating the presence of an endothelial dysfunction condition, by applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude arterial blood flow therein; maintaining the occluding pressure for a predetermined time period; removing the occluding pressure after the elapse of the predetermined time period to restore arterial blood flow; monitoring a digit of the arm or leg by a digit-probe for changes in the peripheral arterial tone therein before and after the application of the occluding pressure to the arm or leg of the patient; and utilizing any detected changes in the peripheral arterial tone for evaluating endothelial activity in the patient. Particularly important advantages are provided when the occluding cuff is applied to the digit of the patient receiving the monitoring digit-probe, on the proximal side thereof with respect to the patient's heart, and also when a reference digit-probe is applied to another digit, not influenced by the occluding pressure, to compensate for shifts inherent to vascular beds.

The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Compounds and methods are provided for treating patients suffering from any of hypercholesterolemia, vascular oxidative stress and endothelial dysfunction.

A compound having the structureuseful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina pectoris, thromboses, restenoses, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver in a human or animal patient.

A method and apparatus for non-invasively evaluating endothelial activity in a patient, particularly for indicating the presence of an endothelial dysfunction condition, by applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude arterial blood flow therein; maintaining the occluding pressure for a predetermined time period; removing the occluding pressure after the elapse of the predetermined time period to restore arterial blood flow; monitoring a digit of the arm or leg by a digit-probe for changes in the peripheral arterial tone therein before and after the application of the occluding pressure to the arm or leg of the patient; and utilizing any detected changes in the peripheral arterial tone for evaluating endothelial activity in the patient. Particularly important advantages are provided when the occluding cuff is applied to the digit of the patient receiving the monitoring digit-probe, on the proximal side thereof with respect to the patient's heart, and also when a reference digit-probe is applied to another digit, not influenced by the occluding pressure, to compensate for shifts inherent to vascular beds.

The invention describes novel nitrosated and / or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and / or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and / or nitrosylated, and, optionally, at least one nitric oxide donor compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and / or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (l) treating nephropathy.

A method and system for use in measuring the endothelial dysfunction utilizing flow mediated dilation and determining arterial health of a patient. The system includes a non-invasive blood pressure monitor, an ultrasound system and a pulse oximeter monitor that all communicate with each other to perform the flow mediated dilation. Initially, the ultrasound transducer, blood pressure cuff and pulse oximeter sensor are positioned on an arm of the patient. The blood pressure cuff is inflated to occlude an artery for an occlusion period. Following the occlusion period, the ultrasound system is automatically signaled to begin determining a parameter of the artery, such as diameter, and the flow rate of blood through the artery without any operator intervention. At the same time, the pulse wave velocity PWV is calculated between the ultrasound transducer and the finger probe of the pulse oximeter following the occlusion period. Based upon the detected characteristics of the artery before and after occlusion, as well as the PWV, the system can determine the endothelial dysfunction and arterial health of the patient.

The present invention is directed to a method of simultaneously treating hypertension, hypertriglyceridemia, a pro-inflammatory state, a pro-coagulative state, and insulin resistance (with or without treating obesity or endothelial dysfunction), associated with or independent from Metabolic Syndrome, comprising the step of administering to a patient suffering from such disorders a therapeutically effective amount of a central acting dopamine agonist. In one embodiment, the central acting dopamine agonist is bromocriptine, optionally combined with a pharmaceutically acceptable carrier.

The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and / or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and / or nitrogen via a bond or moiety that cannot be hydrolyzed.

The present invention concerns methods for treating and preventing renal / kidney disease, insulin resistance / diabetes, fatty liver disease, and / or endothelial dysfunction / cardiovascular disease using synthetic triterpenoids, optionally in combination with a second treatment or prophylaxis.

The combination of a HMG CoA reductase inhibitor like a statin, such as simvastatin, with a pFox inhibitor such as trimetazidine (“Simetazidine”) is particularly advantageous for treatment of end-stage complications, such as acute coronary syndrome (ACS) and chronic angina, especially in type II diabetics. The combination therapy is also useful in the treatment and / or prevention of chronic heart failure (CHF) and peripheral arterial disease (PAD). The combination of a nitric oxide (NO) mechanism with increased NO production with pFox inhibition simultaneously treats both the effect and the cause of angina. One or more oral hypoglycemic compounds (biguanides, insulin sensitizers, such as thiazolidinediones, α-glucosidase inhibitors, insulin secretagogues, and dipeptidyl peptidase IV inhibitors), protein kinase C (PKC) inhibitors, and acetyl-CoA carboxylase inhibitors can also be used in combination with the HMG CoA reductase inhibitors and / or pFox inhibitors, especially in type II diabetics, to control glucose levels and treat endothelial dysfunction. The drugs can be given in combination (e.g. a single tablet) or in separate dosage forms, administered simultaneously or sequentially. In the preferred form the statin is given in a dose of between 5 and 80 mg / day in two separate doses, and the pFox inhibitor is administered in a sustained or extended dosage formulation at a dose of 20 mg three times a day or 35 mg two times a day. The dose of the oral hypoglycemic, PKC inhibitor, or acetyl-CoA carboxylase inhibitor varies with the type of drug used.

Methods are provided for preventing or treating risk factors for cardiovascular disease in an individual, comprising administering a therapeutically effective amount of a composition comprising an estradiol metabolite to said individual. Such risk factors include obesity, the metabolic syndrome, diabetes mellitus, vascular disorders, and renal disorders. Preferred estradiol metabolites include 2-methoxyestradiol, 4-methoxyestradiol, 2-hydroxyestradiol, and 4-hydroxyestradiol or prodrugs thereof. The compositions may also be in the form of a controlled release formulation. Methods are also provided for use of estradiol metabolites to treat or prevent insulin resistance, vascular endothelial dysfunction, hyperlipidemia, hypertension, diabetic nephropathy, proteinuria and reducing leptin levels. In addition, the methods provide a method of stabilizing glucose levels. These treatments may be used in either gender because of their lack of a feminizing estrogenic effect.

Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.

The present invention includes delivery of isolated and purified nucleic acids that encode GTPCH proteins in nanoparticles for the treatment of endothelial cells damaged by diabetes, smoking, dyslipidemia, hypertension, and cardiovascular disease. The nanoparticles contain a nucleic acid sequence, polymer and a targeting ligand. The targeting ligand facilitates the selective delivery of the nucleic acid sequence to damaged endothelial cells. Examples involving a nucleic acid sequence encoding GTP-cyclohydrolase I (GTPCH), PEG / PEI polymers, and a monoclonal antibody or other molecule that binds to the lectin-like oxidized low density lipoprotein (LDL) receptor-1 (Lox-1) or associated molecules are presented.

The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and / or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and / or nitrogen via a bond or moiety that cannot be hydrolyzed.

The invention discloses a blood flowing detection device and method. The detection device comprises an inflation pressure binding belt, a detection host, as well as a temperature sensor and a humidity sensor which are connected with the detection host; and the detection host comprises a control button, a switching voltage-stabilized power supply circuit, a singlechip microcomputer central control-processing unit, a preamplifier, an A / D (analog-to-digital) conversion circuit, a display and a buzzer. The detection method comprises the following steps: releasing restriction after a blood flow atthe proximal end of a heart is restrained for a certain period of time; measuring changes of skin temperature and humidity on a position at a distal end of the heart, and comparing the changes with the standard parameters of people with a normal blood flowing condition; determining whether a testee has vascular endothelial dysfunction or not; and evaluating the severity of early symptoms of cardiovascular sclerosis and hemodynamics of the testee. The detection device has the advantages of simple structure, low cost and convenience for operation, causes no trauma or pain, and can be used for routine physical examination and community general examination.

The invention describes novel organic nitric oxide enhancing salts of nonsteroidal antiinflammatory drugs (NSAIDs) and novel compositions comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders; (c) facilitating wound healing; (d) treating gastrointestinal, renal and / or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; (e) treating inflammatory disease states and / or disorders; (f) treating ophthalmic disorders; (h) treating peripheral vascular diseases; (i) treating diseases resulting from oxidative stress; (j) treating endothelial dysfunctions; and (k) treating diseases caused by endothelial dysfunctions. The organic nitric oxide enhancing compounds that form salts with the NSAIDs are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and / or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and / or oxatriazole-5-imines.

Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.

Various clinical uses for L-arginine complexes are presented. The active agents have individual and complementary physiological functions especially as these relate to conditions and functions, which influence endothelial biochemistry and physiology. The active components of the invention are selected for inclusion in unique combinations that will clinically reduce risks of vasculopathy in various diseases. The reduction of endothelial dysfunctional risks, often associated with aging and generalized poor vascular health and function, will maximize the potential clinical therapeutic success of other mediations and concurrently avoid some risks of pharmaceutical side effects.

The invention describes novel compositions comprising at least one apocynin compound or a pharmaceutically acceptable salt thereof, and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The invention also provides novel kits comprising at least one apocynin compound or a pharmaceutically acceptable salt thereof, and at least one nitric oxide donor compound, and, optionally, at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating gastrointestinal disorders; (h) treating inflammatory disorders; and (j) treating respiratory disorders. The apocynin compound may preferably be apocynin. The nitric oxide donor compound may preferably be isosorbide dinitrate and / or isosorbide mononitrate.

The invention describes novel diuretic compounds comprising at least one heterocyclic nitric oxide donor group, or pharmaceutically acceptable salts thereof, and novel composition comprising at least one diuretic compound comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and / or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidatives stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; and (p) treating sexual dysfunctions. The heterocyclic nitric oxide donors are preferably furoxans, sydnonimines, oxatriazole-5-ones and / or oxatriazole-5-imines.