Abstract: The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macromer or oligomer comprises of repeat units derived from safe and biocompatible molecules such as glycolic acid, lactic acid, caprolactone and p-dioxanone. Furthermore, the present invention relates to controlled release of nitric oxide (NO) and/or drug molecule from a NO and drug releasing macromer or oligomer. Moreover, the present invention also relates to medical devices, medical device coatings and therapeutic formulations comprising of nitric oxide and drug releasing macromers and oligomers of the present invention.

Abstract: The present invention relates to semisolid transdermal pharmaceutical preparation having enhanced stability and bioavailability, wherein the particles are coated by a volatile silicon oil component and the thus obtained suspension is dispersed in a gel or cream base.

Abstract: Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.

Abstract: 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; and (k) treating peripheral vascular diseases. The apocynin compound may preferably be apocynin.

Abstract: The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macromer or oligomer comprises of repeat units derived from safe and biocompatible molecules such as glycolic acid, lactic acid, caprolactone and p-dioxanone. Furthermore, the present invention relates to controlled release of nitric oxide (NO) and/or drug molecule from a NO and drug releasing macromer or oligomer. Moreover, the present invention also relates to medical devices, medical device coatings and therapeutic formulations comprising of nitric oxide and drug releasing macromers and oligomers of the present invention.

Abstract: Bethanechol, diltiazem, or a combination thereof is administered locally to the anus for the treatment of benign anal disorders, in particular anal fissures and hemorrhoids. The agents induce a reduction in the mean and resting pressure, thereby assisting in the healing of the anal fissures and hemorrhoids.

Abstract: A pharmaceutical preparation containing the active substance glyceryl trinitrate having improved storage stability in a container. The improved storage stability is achieved by the addition of a proton-absorbing substance either as part of the preparation as placed into the container or applied to the surface of the preparation's storage container before the remaining components of the preparation are placed into the container. The preparation can preferably be filled into a plastic bottle having a spray pump.

Abstract: There is provided amino acid ester compounds comprising at least one nitric oxide releasing group, pharmaceutically acceptable salts thereof and compositions thereof. These compounds involve an amino acid side-chain or an amino acid derivative thereof and a nitric oxide releasing group as depicted in the following structures: wherein R1 is either an ethyl or an amino acid side-chain group or an amino acid derivative thereof and R2 is an amino acid side-chain group or an amino acid derivative thereof and n is an integer from 1 to 10.

Abstract: Disclosed herein are novel compositions and methods for treating or preventing a variety of disorders and conditions associated with lipid metabolism. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more fibric acid or statin derivative compositions alone or in combination with one or more lipid altering agents and/or PDE inhibitors.

Abstract: The present invention relates to treatment and prevention devices and regimens for tendon injury and damage. The invention further provides compositions comprising therapeutic agents and the use of such compositions in methods of treating disorders, injuries and conditions beneficially treated by these agents, particularly those relating to the management of tendon damage.

Abstract: Alkyl nitrate ester compounds are provided for the delivery of nitric oxide to targeted muscle tissues, and in particular, to normal and dystrophic muscles. In one aspect, nitrate ester compounds are provided having the following formula: wherein, R1 is ONO2, CH2ONO2, CnH2n+1OH, CnH2n+1OH, or CH2CH2CH3, or H; R2 is ONO2, CH2ONO2, Cn?H2n?+1OH, Cn?H2n?+1OH, CH2CH2CH3 or H; and R3 is ONO2, CH2ONO2, Cn??H2n?+1OH, Cn?H2n?+1OH, CH2CH2CH3 or H; wherein n is an integer from 0 to 9, n? is an integer from 0 to 9, and n? is an integer from 0 to 9, and n+n?+n??9, and wherein at least one of R1, R2, and R3 is an ester nitrate selected from the group consisting of ONO2, CH2ONO2, and combinations thereof.

Abstract: Treatment of or prophylaxis against the occurrence of pulmonary disorders associated with hypoxemia and/or smooth muscle constriction or infection in the lungs comprises administration into the lung(s) as a gas composition comprising nitric oxide, e.g. ethyl nitrite or nitric oxide, and also administering into the lungs L-cysteine. The pulmonary disorder can be persistent pulmonary hypertension of the newborn to increase SpO2 and decrease systolic blood pressure. In another case administration is to a premature newborn to prophylax against the development of bronchopulmonary dysplasia.

Abstract: Patients having a disease associated with high level of thioredoxin system activity or a requirement for nitric oxide, e.g. large cell lymphoma or restenosis, are treated with a thioredoxin reductase inhibitor, e.g. auranofin or arsenic trioxide, and a nitric oxide donating compound, e.g. isosorbide mononitrite or isosorbide dinitrite or nitroglycerin or S-nittrosothiol. Patients having a disease associated with nitric oxide synthase overexpression or increased activity, e.g. Parkinson's disease or septic shock or pancreatic cancer, are treated with Trx/Trx reductase upregulator, e.g. aptamer that binds to thioredoxin reductase inhibitor, and agent causing depletion of nitric oxide (or adduct thereof), e.g. L-NMMA or L-NAME or minocycline or ascorbate or N-acetylcysteine.

Abstract: The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders comprising administration of novel compositions comprising at least one nitrosated NSAID, 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.

Abstract: Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.

Abstract: The present invention relates to new napthylene inhibitors of cyclooxygenase activity, pharmaceutical compositions thereof, and methods of use thereof

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: The present invention relates to methods and formulations for inhibiting, treating and preventing a malignant cell phenotype, cell, tumor and/or disease. Administration of nitric oxide mimetics, such as low doses, is sufficient to increase, restore or maintain nitric oxide-mediated signaling in cells so that malignant cell phenotypes, cells, tumors and/or diseases are inhibited or prevented. These methods and formulations are particularly useful in treating and preventing cancer in animals.

Abstract: The invention relates methods of reducing the risk or preventing the occurrence of an adverse event (AE) or a serious adverse event (SAE) associated with a medical treatment comprising inhalation of nitric oxide.

Abstract: A new class of anti-microbial agents and methods for preventing or reducing the risk of sexually transmitted infections and/or diseases is provided. Preferably, these anti-microbial agents are also contraceptive and, thus, also prevent or reduce the risk of unplanned pregnancies. The anti-microbial agents comprise a delivery vector having anti-microbial activity (and preferably contraceptive activity) coupled with a nitric oxide donor moiety.

Abstract: There is provided novel amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one amino acid ester compound comprising at least one nitric oxide releasing group, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. Also provided are compositions for increasing nitric oxide physiological levels in a subject, methods for increasing nitric oxide physiological levels in a subject, methods for improving a subject's muscle strength, athletic performances and/or lean body mass gain and or performance in a subject.

Abstract: The present invention relates to pharmaceutical compositions comprising a ? (1-3) ? (1-4) glucan and a pharmaceutically active agent or a botanical extract. A method to extract and purify cereal ?-glucan is also described. The high purity of the cereal ?-glucan obtained according to the present invention allows for the preparation of clear, colourless viscous liquid preparations. These liquid preparations are stable to gelling effects when kept at ambient temperatures and low ash concentrations, and can be used to prepare the pharmaceutical compositions of the present invention.

Abstract: A composition suitable for the local delivery of cosmetic and/or pharmaceutical agents into the skin containing at least two biocompatible organic solvents, a polar lipid, a surfactant, water, urea and a thickener wherein the organic solvents include an ester and a dihydric and/or polyhydric alcohol is provided.

Abstract: The present invention relates to compositions comprising a nitric oxide releasing paracetamol and an anticonvulsant drug. The compositions of the invention can be used use in the treatment of neuropathic pain in particular diabetic neuropathic pain, painful post-infarct syndrome, pain caused by chemotherapeutic treatment or pain arising from infections by viral agents.

Abstract: The present invention claims and discloses a pharmaceutical composition suitable for oral administration, in form of an emulsion pre-concentrate, comprising (i) a compound of the formula (I) (ii) one or more surfactants; (iii) optionally an oil or semi-solid fat; said composition forming an in-situ oil-in-water emulsion upon contact with aqueous media such as gastrointestinal fluids. The composition may optionally also comprise one or more short-chain alcohols. The pharmaceutical composition is useful in the treatment of pain and inflammation.

Abstract: The present invention relates to the use of 4-(nitrooxy)-butyl-(S)-2-(6-methoxy-2-naphthyl)-propanoate (naproxcinod) for the treatment of pain and/or inflammation in patients with hypertension treated with renin-angiotensin system blocking agents.

Abstract: A pharmaceutical preparation containing the active substance glyceryl trinitrate having improved storage stability in a container. The improved storage stability is achieved by the addition of a proton-absorbing substance either as part of the preparation as placed into the container or applied to the surface of the preparation's storage container before the remaining components of the preparation are placed into the container. The preparation can preferably be filled into a plastic bottle having a spray pump.

Abstract: The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macromer or oligomer comprises of repeat units derived from safe and biocompatible molecules such as glycolic acid, lactic acid, caprolactone and p-dioxanone. Furthermore, the present invention relates to controlled release of nitric oxide (NO) and/or drug molecule from a NO and drug releasing macromer or oligomer. Moreover, the present invention also relates to medical devices, medical device coatings and therapeutic formulations comprising of nitric oxide and drug releasing macromers and oligomers of the present invention.

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 present invention relates to nitrooxyderivative of antioxidant compounds of formula (I) and pharmaceutically acceptable salts or stereoisomers thereof for the treatment of chronic pain, in particular chronic neuropathic pain. The invention also describes composition comprising a nitrooxyderivative of a antioxidant compound of formula (I) and an analgesic drugs.

Abstract: Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric form of Nicotine, nicotinic acid analogs thereof, their combination with or without other pro-angiogenesis factors, vasodilator, or other therapeutic modalities to promote angiogenesis in the subject. This is composition and combination thereof is applicable to improving wound healing, erectile dysfunction, improving collateral or blood supply in patients with myocardial infarction, stroke, peripheral artery diseases, and other vascular disorders as disclosed.

Abstract: The present invention refers to a process for preparing a compound of general formula (A), as reported in the description, wherein R is a radical of a drug and R1-R12 are hydrogen or alkyl groups, m, n, o, q, r and s are each independently an integer from 0 to 6, and p is 0 or 1, and X is O, S, SO, SO2, NR13 or PR13 or an aryl, heteroaryl group, said process comprising reacting a compound of formula (B) R—COOZ (B) wherein R is as defined above and Z is hydrogen or a cation selected from: Li+, Na+, K+, Ca++, Mg++, tetralkylammonium, tetralkylphosphonium, with a compound of formula (C), as reported in the description, wherein R1-R12 and m, n, o, p, q, r, s are as defined above and Y is a suitable leaving group.

Abstract: There is provided novel amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one amino acid ester compound comprising at least one nitric oxide releasing group, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. Also provided are compositions for increasing nitric oxide physiological levels in a subject, methods for increasing nitric oxide physiological levels in a subject, methods for improving a subject's muscle strength, athletic performances and/or lean body mass gain and or performance in a subject.

Abstract: The present invention relates to methods and formulations for inhibiting, treating and preventing a malignant cell phenotype, cell, tumor and/or disease. Administration of nitric oxide mimetics, such as low doses, is sufficient to increase, restore or maintain nitric oxide-mediated signaling in cells so that malignant cell phenotypes, cells, tumors and/or diseases are inhibited or prevented. These methods and formulations are particularly useful in treating and preventing cancer in animals.

Abstract: The invention relates to a method of treatment for muscular dystrophies, including Duchenne, Becker, limb-girdle, facioscapulohumeral, congenital muscular dystrophies and the like using a combination of nitric oxide-releasing and anti-inflammatory compounds.

Abstract: Use for the treatment of diseases having an inflammatory basis of compounds or salts thereof, Having the following general formula (I): A—X1—L—(W)p—NO2 wherein A contains the radical of a drug, X1 and W are bivalent radicals, L is a covalent bond or oxygen, sulphur, NR1e wherein R1e is H or a C1-C5 linear or branched alkyl.

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: 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, Formula (I). The invention also encompasses certain pharmaceutical compositions and methods for treating cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula 1. 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: The present invention relates to improved therapies for the treatment of heart disease, particularly the improved delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method of treating or preventing a cardiovascular disease by transfecting cardiac cells of a large mammal, the method comprising, identifying a mammal in need of treatment or prevention of heart disease, supplying NO to the coronary circulation prior to, and/or during the infusion of a therapeutic polynucleotide into a blood vessel of the coronary circulation in vivo, where the therapeutic polynucleotide is infused into the blood vessel over a period of at least about three minutes, where the coronary circulation is not isolated or substantially isolated from the systemic circulation of the mammal; and where the therapeutic polynucleotide transfects cardiac cells of the animal resulting in the treatment or prevention of the heart disease.

Abstract: The formulation provides a method of treating headaches, neck, joint and inflammatory-type pain in a mammalian subject by administering to the subject a therapeutically effective amount of a nitrate-containing compound and a therapeutically effective amount of a selenium-containing compound. The formulation also provides kits and systems for practicing the subject methods.

Abstract: The present invention is directed to methods and compositions which include nitrate amino acid chelates that can increase the metabolic activity or metal concentration in animals and that can increase metabolic activity and nitrogen content in plants. In one embodiment, a nitrate-complexed amino acid composition can comprise a metal, an amino acid ligand, and a nitrate, wherein the amino acid ligand is chelated to the metal forming an amino acid chelate and the nitrate is complexed to the amino acid chelate. In another embodiment, a nitrate-chelated amino acid composition can comprise a metal, an amino acid ligand, and a nitrate, wherein the amino acid ligand and the nitrate are chelated to the metal forming a nitrate-chelated amino acid chelate.

Abstract: The present invention relates to a new process for the preparation of NO-donating compounds using a sulfonated intermediate. The invention relates to new intermediates prepared therein suitable for large scale manufacturing of NO-donating compounds. The invention further relates to the use of the new intermediates for the manufacturing of pharmaceutically active NO-donating compounds. The invention further relates to a substantially crystalline form of NO-donating NSAIDs, especially 2-[2-(nitrooxy)ethoxy]ethyl {2-[(2,6-dichlorophenyl)amino]phenyl}acetate, the preparation thereof and to pharmaceutical formulations containing said crystalline form and to the use of said crystalline form in the preparation of a medicament.

Abstract: The present invention relates to the use of the following compounds, their compositions, and their salts for the preparation of medicaments for the treatment of urinary incontinence and other diseases, the compounds having the general formula: A-X1—NO2 wherein: A=RCO(X)t, wherein t is the integer 0 or 1; X?O, NH, NR1C, wherein R1C is a linear or branched C1 to C10 alkyl group; when t=1, R= and X1=—YO—, wherein Y is a C1 to C20 alkylene, C5 to C7 cycloalkyl or oxyalkyl derivative.

Abstract: Use for the treatment of diseases having an inflammatory basis of compounds or salts thereof, having the following general formula (I): A-X1-L-(W)p-NO2 wherein A contains the radical of a drug, X1 and W are bivalent radicals, L is a covalent bond or oxygen, sulphur, NR1c wherein R1c is H or a C1-C5 linear or branched alkyl.

Abstract: The invention is directed to a method for treating a cyclooxygenase-2 mediated disease or condition in a mammalian patient at risk of a thrombotic cardiovascular event, wherein the patient is on aspirin therapy to reduce the risk of the thrombotic cardiovascular event, comprising orally concomitantly or sequentially administering to the patient a cyclooxygenase-2 selective inhibitor in an amount effective to treat the cyclooxygenase-2 mediate disease or condition, and a nitric oxide donating compound in accordance with Formula I or a pharmaceutically acceptable salt thereof, wherein the nitric oxide donating compound is administered in an amount effective to reduce the gastrointestinal toxicity caused by the combination of the cyclooxygenase-2 selective inhibitor and aspirin. Pharmaceutical compositions are also encompassed.

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. Formula (I). The invention also encompasses certain pharmaceutical compositions and methods for treating cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula 1. 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: Use for the treatment of diseases having an inflammatory basis of compounds or salts thereof, Having the following general formula (I): A-X1-L-(W)p—NO2 wherein A contains the radical of a drug, X1 and W are bivalent radicals, L is a covalent bond or oxygen, sulphur, NR1e wherein R1e is H or a C1-C5 linear or branched alkyl.

Abstract: Use for the diabetes treatment of compounds or salts thereof, having the following general formula (I): A-(B)b0—(C)c0—NO2 wherein A contains the radical of a drug having an antiinflammatory or analgesic activity, B is a bivalent linking group wherein the precursor must meet the tests described in the application, C is a a bivalent linking group as defined in the invention.

Abstract: The present invention provides methods for stabilizing, reducing or eliminating cancer cells. In particular, the present invention provides prophylactically and/or therapeutically effective regimens for the prevention, treatment and/or management of cancer, the regimens comprising administering one or more cancer therapies to a subject to reduce a cancer cell population. The therapy(ies) in the prophylactically and/or therapeutically effective regimen can be administered at a lower dose than currently used or known to one of skill in the art and/or for a longer period of time and/or more frequently than currently administered or known to one of skill in the art.

Abstract: A composition for topical application to a part of the body comprises a vasodilator, for example glyceryl trinitrate, as active ingredient dissolved in a blend of volatile and non-volatile solvents of different solvating capacities for the vasodilator. The vasoldator is present in the composition at a concentration at or slightly below saturation, whereby evaporation of the volatile solvent in use will maintain the vasodilator at saturated or super-saturated concentrations in the residue, whereby the vasodilator will become saturated or supersaturated in the solvent remaining and, as the active ingredient passes through the skin and is absorbed in the bloodstream, and thus becomes depleted in the residual composition, continuing evaporation of volatile solvent will maintain the active ingredient substantially at saturation or supersaturation level in the residual composition throughout the major part of the absorption phase, thereby maximising absorption levels but at a moderate dosage level.