Abstract: A patient with dyslipidemia is treated with a cholesterol blood level lowering effective amount of a non-statin cholesterol lowering agent and an amount of nitric oxide (NO) donating compound effective to mediate increase in nitric oxide bioactivity in blood.

Abstract: Statin nitroderivatives having improved pharmacological activity and enhanced tolerability are described. They can be employed for treating and/or preventing several diseases, in particular coronary syndromes, neurodegenerative disorders as well as for reducing cholesterol levels.

Abstract: A method for preventing or reducing hemispheric cerebral oxygen desaturation in a subject undergoing surgery, wherein the method comprising the prophylactic administration of a vasodilator to the subject.

Abstract: The present invention provides methods of treating or preventing vascular diseases caused by nitric oxide (NO) insufficiency. The methods encompass administering a composition comprising an antioxidant, a compound to treat cardiovascular diseases, a nitrosated compound, a compound that donates, transfers or relases NO, or is a NO synthase substrate, or endogenously stimulates NO synthesis, or stimulates levels of endothelium derived relaxing factor. In the said composition, a hydralazine compound may be an antioxidant, isosorbide mono-or dinitrate may be the compound to donate, transfer, release, or stimulate endogenous NO synthesis. The isorsorbide may also elevate endogenous levels of endotherlium-derived relaxing factor, or be a NO synthase substrate and angiotensin enzyme inhibitor may be nitrosated compound.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and methods for treatment of cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I.

Abstract: Compounds or their salts of general formula (I): A—B—N(O)s wherein: s is an integer equal to 1 or 2; A=R—T1—, wherein R is the drug radical and T1=(CO)t or (X)t?, wherein X=O, S, NR1c, R1c is H or a linear or branched alkyl or a free valence, t and t? are integers and equal to zero or 1, with the proviso that t=1 when t?=0; t=0 when t?=1; B=—TB—X2—O— wherein TB=(CO) when t=0, TB=X when t?=0, X being as above defined; X2 is equal to R1B—X—R2B radical wherein X is as above defined, R1B and R2B, equal to or different from each other, are linear or branched C1–C6 alkylenes, or X2 is a radical wherein two alkylene chains C1–C4 are linked to nonadjacent positions of a central ring having 4 or 6 atoms, said ring being an unsaturated cycloaliphatic ring, or a saturated or aromatic heterocylic ring, containing one or two heteroatoms, equal or different, selected from O, S, N; wherein the unsaturated cycloaliphatic ring does not have aromatic character according to Huckel's rule.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and methods for treating cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I. The above compounds may be used as a combination therapy with low-dose aspirin to treat chronic cyclooxygenase-2 mediated diseases or conditions while also reducing the risk of thrombotic cardiovascular events.

Abstract: Statin nitroderivatives having improved pharmacological activity and enhanced tolerability are described. They can be employed for treating and/or preventing several diseases, in particular coronary syndromes, neurodegenerative disorders as well as for reducing cholesterol levels.

Abstract: The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhi

Abstract: Probucol derivatives and pharmaceutical compositions containing the same to be employed in treatment or prophylaxis of diseases.

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.

Abstract: Disclosed are (i) compounds of a steroid, a ?-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, ?-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO?), or as the neutral species, nitric oxide (NO.) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.

Abstract: Methods and therapeutic compounds for treating pain, mitigating inflammation, effecting analgesia and/or effecting sedation in a subject are described. A subject is administered an effective amount of a therapeutic compound which is a nitrate ester. Novel pharmaceutical compositions are also described.

Abstract: The present invention provides methods for treating a variety of urogenital disorders, such as, for example, vaginismus, dyspareunia, vulvodynia (including vulvar vestibulitis), interstitial cystitis, nonspecific urethriris (i.e., nonspecific pain and/or burning of the urinary tract) and sexual dysfunctions, such as, for example, female sexual arousal disorders and female sexual orgasmic disorders, using a variety of compounds, including, but not limited to, NO donors, calcium channel blockers, cholinergic modulators, ?-adrenergic receptor antagonists, ?-adrenergic receptor agonists, phosphodiesterase inhibitors, cAMP-dependent protein kinase activators (e.g.

Abstract: Methods and formulations for inhibiting and preventing a malignant cell phenotype by administering to cells a low dose of a nitric oxide mimetic are provided.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: 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.

Abstract: Preeclampsia and preterm labor in a pregnant female mammal are treated by administering thereto a combination of a progestin and a nitric oxide synthase substrate, a nitric oxide donor or both, optionally in further combination with one or more of a cyclooxygenase inhibitor, a PGI2-mimetic, a thromboxane (TXA2) inhibitor, a compound possessing TXA2-agonistic and TXA2-inhibiting properties, a compound possessing TXA2-antagonistic and PGI2-memetic activities, and a TXA2 antagonist.

Abstract: The present invention relates to pharmaceutical compositions comprising, as an anticancer agent (a) one or more compounds having the formula NO2-A-B, wherein A is a saturated or unsaturated hydrocarbon chain of 14-26 double bonds, and B is (CH2)m(COOH)n in which n is an integer from 0 to 2 and m is an integer from 0 to 2; or a derivative thereof in which the hydrocarbon chain has one or more than one substitution selected from the group consisting of hydroxy, hydroperoxy, epoxy and peroxy; (b) one or more compounds selected from polyunsaturated fatty acids (PUFA's) having a 16 to 26 carbon atom chain and 3 to 6 double bonds, and wherein the PUFA is covalently coupled at the carboxylic acid group to an amino acid selected from glycine and aspartic acid; (c) one or more compounds selected from unsaturated fatty acids having an 18 to 25 carbon atom chain and 1 to 6 double bonds and wherein the fatty acid has one or two &bgr;-oxa, &ggr;-oxa, &bgr;-thia, &ggr;-thia substitutions; or (d) one or more compounds havin

Abstract: The present invention claims and discloses a pharmaceutical composition suitable for oral administration, in form of an emulsion pre-concentrate, comprising(i) one or more NO-releasing NSAID(s);(ii) one or more surfactants, of which at least one is phospholipid; said composition forming an in-situ oil-in-water emulsion upon contact with gastrointestinal fluids. The composition may optionally also comprise an additional oil or semi-solid fat. Further, one or more short-chain alcohols can optionally be included in the composition. Also within the scope of the invention is a combination with a proton pump inhibitor. The pharmaceutical composition is useful in the treatment of pain and inflammation. Further within the scope of the invention is kit comprising a pharmaceutical composition according to the invention in a unit dosage form, in combination with a proton pump inhibitor, and said proton pump inhibitor is enteric coated.

Abstract: Use of organic compounds containing the —ONO2 function, or inorganic compound containing the —NO group or compositions comprising said compounds to reduce the toxicity caused by drugs to the gastrointestinal and/or renal apparatus, said compounds being characterized in that they are nitric oxide NO donors i.e., when they are put into contact in vitro with cells of the vasal endothelium or platelets.

Abstract: A sustained release formulation of L-arginine alone or in combination with an agent which enhances the biotransformation of L-arginine into NO is described herein.

Abstract: The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, &agr;1-adrenergic receptor antagonists, &bgr;-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors.

Abstract: The present invention is directed to a method of treating disordered control of breathing including the treatment of apnea and hypoventilation associated with congenital or acquired brain stem abnormalities. Specifically the invention is directed to treating disordered control of breathing by administering an S-nitrosylating agent selected from the group consisting of ethyl nitrite, glutathione, nitric oxide, S-nitrosocysteine, S-nitrosoglutathione, S-nitro-N-acetyl cysteine. As shown in FIG. 1C the ability of endogenous SNOg to increase VE in freely behaving, conscious rates using whole-body plethysmography revealed that CSNO, GSNO and CGSNO (1 nmol each) caused equivalent increases in VE, whereas D-CSNO had no effect (left bar graph is the equivalent increases in VE, whereas D-CSNO had no effect (left bar graph is the control whereas the right bar represents administration of the respective SNO).

Abstract: The occurrence of hypercapneic acidosis in a fetus during a laparoscopic procedure carried out on a pregnant female, is prevented or ameliorated by inclusion in or addition to the carbon dioxide insufflation gas, of a nitric oxide donor, e.g., ethyl nitrite. Administration of nitric oxide donor in insufflation gas causes increase in fetal cerebral oxygenation.

Abstract: Vessels are treated with a mixture of L-arginine and an agent which enhances the biotransformation of L-arginine into NO. The incidents associated with restenosis are expected to be substantially reduced and prevented providing for a reduced incidence of restenosis as a result of the injury.

Abstract: The invention compounds and methods for the treatment of motor disorders. In particular, the invention provides eicosanoid analogs which are effective in ameliorating motor disorders such as spasticity caused by multiple sclerosis (MS).

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases.

Abstract: It is intended to provide medicines having a higher ocular tension-lowering effect on ocular hypertension and glaucoma. Because of showing an excellent effect of lowering ocular tension, medicines comprising a combination of a prostaglandin compound with an NO-donating compound are useful in treating ocular hypertension and glaucoma.

Abstract: Nitro-oxyderivative compounds or salts thereof having the following general formula (I): A-(B)b0-(C)c0-NO2 wherein: c0 is an integer and is 0 or 1, b0 is an integer and is 0 or 1, A=R-T1-, wherein R is the radical of an analgesic drug for the chronic pain, in particular for the neuropathic pain; B is such that its precursor is selected from anminoacids, hydroxyacids, polyalcohols, compounds containing at least one acid function; C is a bivalent radical containing an aliphatic, heterocyclic or aromatic radical.

Abstract: The invention provides the combined use of an inhibitor of formation or release of &bgr;-amyloid and a nitric oxide releaser for the treatment or prevention of Alzheimer's disease.

Abstract: This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient.

Abstract: The present invention is based on the discovery that stents can be coated with biodegradable, bioactive polymers that promote endogenous healing processes at a site of stent implantation. The polymers biodegrade over time, releasing agents which establish or re-establish the natural healing process in an artery. Preferably, the stent is implanted at the time an artery is damaged, such at the time of angioplasty to protect the damaged artery against deleterious blood-borne factors that initiate proliferation of smooth muscle cells.

Abstract: The present invention provides X-nitro compound, pharmaceutical compositions of X-nitro compounds and methods of using X-nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease.

Abstract: Compositions and methods to treat or prevent pain, inflammation, or inflammation-related disorder, as well as a neurologic disorder involving neurodegrneration in a subject that is in need of such prevention or treatment involve a combination of a Cox-2 inhibitor and a 5-HT1A receptor modulator.

Abstract: The present invention provides a compound containing at least one sulfhydryl group and at least one NO donor group, wherein said compound contains one or more protected sulfhydryl groups linked to at least one aromatic ring or a heteroaromatic ring with a nitrogen in the ring structure, which ring is substituted by one or more substituents bearing at least one terminal —ONO2 group. The present invention further provides pharmaceutical compositions comprising one or more of said compounds as an active ingredient.

Abstract: A device and method is described for providing sustained vasodilation at a site in a patient. The device includes a biocompatible and possibly biodegradable carrier, and a vasodilator incorporated into the carrier. The vasodilator is present in a topically effective amount to achieve sustained vasodilation at a selected site in a patient. The vasodilator may be nitroglycerine or calcium channel blockers. The carrier includes methylcellulose and equine collagen, and may be in the form of a strip. The method includes administering, at a selected site in a patient, a vasodilator incorporated into a carrier. The vasodilator is present in a topically effective amount to achieve sustained vasodilation at the selected site.

Abstract: Analogs of andandamide and arvanil have been found to act preferential at CB1 and AR1 receptors, and at receptors other than CB1 and AR1. The analogs provide analgesic effects in vivo, and are useful in pain management. In addition, the analogs may be used as anti-proliferative/anti-tumor agents, vasodilators, and in other applications. Several of the anandamide and arvanil analogs are more potent than anandamide and arvanil.

Abstract: A blood-flow decrease preventing agent is used to negate or reduce the decreased oxygen delivery in abdominal organs caused by insufflating gas. Preferably a gas is delivered into the abdominal cavity consisting essentially of the insufflating gas and the blood-flow decrease preventing agent. Very preferably, a gas is used consisting essentially of carbon dioxide as the insulating gas and ethyl nitrite as the blood-flow to abdominal organ decrease preventing agent.

Abstract: A new pharmaceutical composition in the form of lipoglobules which comprises (a) one or more NO-releasing NSAID(s); (b) one or more surfactant(s); and (c) an aqueous phase, as well as a process for the preparation of such composition and the use of such composition in the treatment of pain and inflammation.

Abstract: The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The present invention also provides novel compositions comprising at least one taxane and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The compounds and compositions of the present invention can also be bound to a matrix.

Abstract: Use of the following groups of compounds or their compositions for the preparation of medicaments for the treatment of gastrointestinal tumors, such compounds having general formula: A-X1—NO2 or their salts, where A=R(COX)t and where t is an integer 0 or 1; X═O, NH, NR1c, where R1c is a linear or branched alkyl having from 1 to 10 C atoms; R is (IA) where t=1 and X1 is equal to —YO— where Y is a C1-C20 alkylene, C5-C7 cycloalkyl or oxyalkyl derivatives.

Abstract: The present invention provides methods of treating and/or preventing vascular diseases characterized by nitric oxide insufficiency by administering a therapeutically effective amount of at least one antioxidant, or a pharmaceutically acceptable salt thereof, and at least one of isosorbide dinitrate and isosorbide mononitrate, and, optionally, at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenergic blocker, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist, nitrosated renin inhibitor, and/or at least one compound used to treat cardiovascular diseases. The antioxidant is preferably a hydralazine compound or a pharmaceutically acceptable salt thereof.

Abstract: The invention relates to solid dispersions of nitrate active principles in at least one polymer chosen from the group consisting of polyvinyl pynolidone, cellulose derivatives or polyethylene glycol, their production processes and pharmaceutical formulations including said dispersions.

Abstract: The invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent.

Abstract: Pharmaceutical combinations for treatment and/or prevention of all sorts, periods and complications of diabetes mellitus in mammals, thus including the pre-diabetic diseases and their complications, optionally including furthermore ischaemic heart disease comprising an effective dose of at least one enzymatic nitric oxide (NO) donor active ingredient and optionally comprising an effective dose of at least one antidiabetic active ingredient, and further optionally comprising usual pharmaceutically acceptable carriers and/or other auxiliaries. The combination may consist of more than one pharmaceutical compositions. The effective doses related to the new insulin-sensitizing effect are considerably lower than the usual doses related to the know effect of most active substances dues to metabolic effects that influence insulin sensitivity in healthy and insulin resistant mammals. The usual dose of NO-donors is necessary when the patient has also ischaemic heart disease.

Abstract: 1

Abstract: Methods and formulations for treating dyspareunia are provided. A pharmaceutical composition formulated so as to contain a therapeutically effective amount of nitroglycerin is administered to the vagina or vulvar area of the individual undergoing treatment. Preferred formulations are immediate release formulations in which at least 80% of the nitroglycerin in the formulation is released therefrom within 4 hours following administration. The formulations may contain one or more additional active agents, e.g., agents that are also useful to treat dyspareunia and/or potentiate the action of nitroglycerin. Such additional agents include vasoactive agents such as prostaglandins, phosphodiesterase inhibitors, androgens such as testosterone, estrogens such as estradiol, and selective modulators of estrogen and androgen receptors. A kit for a patient to use in the self-administration of the formulation is also provided.

Abstract: 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.

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.