Abstract: The present invention relates to methods of treating SD associated with hypertension and another condition by administering a pharmaceutical combination of an angiotensin receptor blocker with either an anti-hypertensive drug or an HMG-CoA reductase inhibitor.

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: Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (½ to {fraction (1/20)}) of those known to induce vasodilation in “normal” circulations.

Abstract: There is disclosed pharmaceutical compositions and methods useful in obviating or mitigating tolerance during organic nitrate therapy. The compositions and methods comprise compounds selected from the group comprising a folate compound, a folate derivative compound, tetrahydrobiopterin and mixtures thereof.

Abstract: A device for providing pharmaceutical doses comprising a container, filled with a pharmaceutical composition including a pharmaceutically active agent in a solution of liquified 1,1,1,2-tetrafluoroethane (HFC-134a), or 1,1,1,2,3,3,3 heptafluoropropane (HFC-227) and a carrier. The carrier can be a pharmaceutically acceptable alcohol, polyol, (poly)alkoxy derivative, fatty acid alkyl ester, polyalkylene glycol, or dimethyl sulphoxide. The device includes a valve arranged for delivering aerosol doses of said pharmaceutical composition to the exterior of the container, and at least a portion of the device is formed from a polyester.

Abstract: Methods for enhancing the therapeutic and adjuvant use of IL-12 by reducing unwanted transient immunosuppression caused by IL-12 or by high doses thereof involve co-administering IL-12 with an effective amount of an agent that inhibits or neutralizes nitric oxide (NO) in vivo. Enhanced vaccine therapy involves co-administering the IL-12 adjuvant, a selected vaccine antigen and the NO inhibiting/neutralizing agent. Additionally, the toxicity of IL-12 treatment may be reduced by co-administering IL-12 with an effective amount of the NO inhibiting or neutralizing agent. A therapeutic composition characterized by reduced toxicity in mammals contains IL-12, preferably a low dose thereof, and an NO inhibiting or neutralizing agent in a pharmaceutically acceptable carrier. A vaccine composition contains an effective adjuvanting amount of IL-12, an effective amount of an NO inhibiting or neutralizing agent, and an effective protective amount of a vaccine antigen in a pharmaceutically acceptable carrier.

Abstract: Compositions and methods for the treatment of anorectal disorders are provided in which certain combinations of NO donors, PDE inhibitors, superoxide (O2−) scavengers, &bgr;-adrenergic agonists, cAMP-dependent protein kinase activators, &agr;1-adrenergic antagonists, L-type Ca2+ channel blockers, estrogens, ATP-sensitive K+ channel activators and smooth muscle relaxants are used.

Abstract: A method of treating congestive heart failure in a subject suffering therefrom, comprising administering erythropoietin and intravenously administering an intravenously administrable iron compound to the subject. The iron is preferably administered in the form of a complex of a ferric hydroxide with erythropoietin.

Abstract: Cold storage solutions for the preservation of organs and biological tissues prior to implantation, including a prostaglandin having vasodilatory, membrane stabilizing, platelet aggregation prevention upon reperfusion, and complement activation inhibitory properties, a nitric oxide donor, and a glutathione-forming agent.

Abstract: Nutritional or therapeutic compositions are provided for increasing ketone body levels in the blood of mammals by providing a source of ketone bodies in the form of linear or cyclic oligomers and/or derivatives of 3-hydroxyacids. The 3-hydroxyacid can be in the form of a linear oligomer of 3-hydroxyacids other than linear homo-oligomers of 3-hydroxybutyric acid if administered in combination with acetoacetate, cyclic oligomers of 3-hydroxyacids, esters of the linear or cyclic oligomers, esters of 3-hydroxyacids other than 3-hydroxybutyric acid, and combinations thereof. An oligomer generally refers to a polymer of three or more hydroxyacids. Preferred 3-hydroxyacids include 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, and 3-hydroxyheptanoate. Oligomers of odd-carbon number 3-hydroxyacids such as 3-hydroxyvalerate have advantages since they have a higher energy content than oligomers of 3-hydroxyacids having an even-number of carbons.

Abstract: The present invention provides methods for reducing pain associated with chronic anal fissures with reduced side effects, comprising: contacting an anal area with a composition comprising an effective amount of nitroglycerin, thereby relieving pain associated with anal fissures. It also provides a extremely stable pharmaceutical composition comprising nitroglycerin, propylene glycol, and a non-ionic surfactant, as well as kits.

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 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 relates to a pharmaceutical composition comprising a nitrate vasodilator and a compound of formula I.

Abstract: Nitric oxide donor compounds of the formula: 1

Abstract: A method and a pharmaceutical composition for inhibiting premature rapture of the fetal membranes, ripening of the uterine cervix and preterm labor of female mammals including human. The method includes the step of administering compounds for reversing at least two biochemical conditions being associated with the above processes. The pharmaceutical composition includes compounds for reversing at least two biochemical conditions being associated with the above processes.

Abstract: There is provided a pharmaceutical composition comprising isosorbide dinitrate, wherein said composition is in the form of an aqueous gel containing not more than about 15 wt.% of a water-soluble lipophilic substance. Optionally, the gel may comprise a calcium channel blocker as an additional active ingredient. A composition comprising diisosorbide dinitrate and nifedipine is also disclosed. There is also provided a method for treating anal fissure, comprising applying to a locus in need of such treatment an efficacious amount of a composition according to the invention.

Abstract: The present invention provides compositions useful for the treatment of inflammation in humans, and related methods of treatment for the same.

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 invention provides methods and compositions for promoting neural cell growth and/or regeneration. The general methods involve contacting with an activator of a cyclic nucleotide dependent protein kinase a neural cell subject to growth repulsion mediated by a neural cell growth repulsion factor. The activator may comprise a direct or an indirect activator of the protein kinase; the repulsion factor typically comprises one or more natural, endogenous proteins mediating localized repulsion or inhibition of neural cell growth; and the target cells are generally vertebrate neurons, typically injured mammalian neurons. The subject compositions include mixtures comprising a neural cell, an activator of a cyclic nucleotide dependent protein kinase and a neural cell growth repulsion factor.

Abstract: The present invention relates to fireproof, non-explosive solids mixtures containing nitroglycerin and anhydrous lactose that do not have to be classified as an explosive in accordance with ADR/RID, IATA, IMCO and/or UN guidelines, to methods for the preparation of such solids mixtures and to the use of anhydrous lactose for the preparation of fireproof, non-explosive solid mixtures containing nitroglycerin and lactose that do not have to be classified as an explosive in accordance with ADR/RID, IATA, IMCO and/or UN guidelines.

Abstract: Nitric oxide scavengers, such as dithiocarbamate-containing compounds, are used to reduce side effects caused by therapeutic administration of nitric oxide sources by administering the nitric oxide scavenger(s) to the subject after the therapeutic effect of the nitric oxide source has been achieved. For example, the nitric oxide source can be coadministered with the nitric oxide scavenger, with the latter formulated in a time release vehicle selected to delay release of the scavenger for a period of time sufficient to ensure that the therapeutic goal of the nitric oxide source has been achieved before release of the scavenger. Formulations and kits, including a bubble pack with pairwise arrangement of unit doses of a desired nitric oxide source and nitric oxide scavenger, are also provided.

Abstract: The invention describes the regulation of cervical dilatation and extensibility by the use of nitric oxide donors and/or substrates or nitric oxide inhibitors. There can be used either (a) at least one nitric oxide donor and/or substrate for manufacture of a medicament to be administered locally intracervically or intravaginally for induction of cervical ripening or (b) at least one nitric oxide inhibitor for manufacture of a medicament to be administered locally intracervically or intravaginally for treatment of cercvical insufficiency or preterm labor.

Abstract: Wound healing is impaired in many diabetics, who suffer increased risk of chronic foot ulceration and amputation. Diabetic patients with poor healing ability were found to possess significantly lower fasting urinary nitrate levels than diabetic patients with normal healing ability or non-diabetic controls, implicating decreased endogenous nitric oxide activity as the mediator of diabetes-impaired wound healing. Methods and kits are provided for predicting the wound healing ability of diabetic patients and patients with venous stasis ulceration or another disease or condition characterized by chronically impaired cutaneous wound healing in some patients based on the levels of nitric oxide related products such as nitrate or nitrite in urine or other specimens. Methods are also provided for treating non-wound healing patients and monitoring diabetic ulcer treatment.

Abstract: The present invention describes rapid noninvasive methods for measuring vasodilation or changes in blood flow in a patient following administration of 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 vasoactive agent. The method comprises the administration of 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 vasoactive agent to the patient followed by monitoring the temperature change of an area of interest using infrared thermography.

Abstract: A pharmaceutical composition contains a nitric oxide donor and advantageously an optional corticosteroid and/or topical anesthetic. The composition is useful in a method for treating anal disorders such as anal fissure, anal ulcer, hemorrhoidal disease, levator spasm, and so forth, by topical application to or proximate the affected area.

Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine and enamine derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.

Abstract: Compositions and methods for the treatment of anorectal disorders are provided in which certain combinations of NO donors, PDE inhibitors, superoxide (O2−) scavengers, &bgr;-adrenergic agonists, cAMP-dependent protein kinase activators, &agr;1-adrenergic antagonists, L-type Ca2+ channel blockers, estrogens, ATP-sensitive K+ channel activators and smooth muscle relaxants are used.

Abstract: New camitine derivatives of general formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease.

Abstract: The present invention relates to a pharmaceutical composition comprising a nitrate vasodilator and a compound of formula I:

Abstract: Compounds of the general formula A—X1—NO2, or their pharmaceutical compositions, wherein A contains a prostaglandin residue, X1 is a bivalent connecting bridge.

Abstract: The invention describes novel compounds derived from pentaerythritol of general formula I, XIV, XVI, XIX and XXII, the substituents being as defined in the description, which can be used as pharmaceutical active substances, especially for the treatment of cardiovascular diseases.

Abstract: Liver diseases, such as cirrhosis of the liver, toxic and medicamentary liver damage, a liver-parenchymic disorder or hepatitis, are treated by administering to a human or animal subject in need thereof a therapeutically active or prophylactically effective low dose amount of a vasodilating agent which selectively increases the supply of oxygenated blood to the liver by increasing hepatic arterial inflow; Suitable vasodilating agents include calcium blockers, such as a benzothiazepine derivative, nifedipine, felodipine or verapamil.

Abstract: A method of treating a subject for an unwanted epidermal or dermal condition comprising administering to the subject, a treatment which modulates the level of nitric oxide (NO) in the skin.

Abstract: Compounds and their compositions, of general formula: A--X.sub.1 --NO.sub.2 are used as medicaments wherein: A=R(COX).sub.t t=0 or 1; X=O and the remaining substituents are defined in the specification.

Abstract: A method is provided for the improvement of implantation rates and/or pregnancy rates in a female mammal, comprising administering to a female mammal in whom pregnancy is desired an effective amount of(a) a nitric oxide synthase substrate, a nitric oxide donor, or both, optionally in combination with(b) a progestin, and,(c) optionally, in further combination with an estrogen.A method is also provided for fertility control for a female mammal, comprising administering to a female mammal in whom pregnancy is not desired and at risk for becoming pregnant an effective amount of nitric oxide synthase inhibitor in combination with an antiprogestin. Pharmaceutical compositions are also provided.

Abstract: Compounds of formula (I): in which:R.sub.a and R.sub.b, identical or different, represent hydrogen or alkyl or together form a bond,R.sub.C represents hydroxyl optionally substituted alkoxy, or optionally substituted amino,R.sub.1 represents hydrogen or --O--NO.sub.2, --O--NO, or --S--NO,R.sub.2 and R.sub.3, identical or different, represent hydrogen, alkyl, or optionally substituted phenyl,X represents oxygen or --NH--CO--,m represents 0 or 1,n represents an integer such that 0.ltoreq.n.ltoreq.6,p represents 0 or 1,R.sub.4 represents hydrogen, optionally substituted alkyl, optionally substituted phenyl, or a group as defined in the description,R.sub.5 represents hydrogen or alkyl,R.sub.6 represents hydrogen or alkyl,or R.sub.5 and R.sub.6 together form a chain --(CH.sub.2).sub.t -- in which t represents 1 or 2,q represents 0, 1, or 2,r represents an integer such that 0.ltoreq.r.ltoreq.6,R.sub.d and R.sub.

Abstract: Disclosed are nitrosated and nitrosylated .alpha.-adrenergic receptor antagonists, compositions of an .alpha.-adrenergic receptor antagonist (.alpha.-antagonist), which can optionally be substituted with at least one NO or NO.sub.2 moiety, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.cndot.); and uses for each of them in treating human impotence or erectile dysfunction.

Abstract: This invention relates to methods of treating or controlling a disease or stress condition such as laminitis in a non-human mammal by topically applying to the limb of the mammal a nitrovasodilator and a protective covering dressing in the form of a cuff, sleeve, or boot.

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 PGI.sub.2 -mimetic, a thromboxane (TXA.sub.2) inhibitor, a compound possessing TXA.sub.2 -agonistic and TXA.sub.2 -inhibiting properties, a compound possessing TXA.sub.2 -antagonistic and PGI.sub.2 -memetic activities, and a TXA.sub.2 antagonist.

Abstract: Dysmenorrhea, disfunctional uterine bleeding, preterm labor and postpartum labor in female mammals are treated by inhibiting uterine contractility by administering thereto a nitric oxide synthase substrate, a nitric oxide donor or both, optionally in combination with one or more of a prostaglandin inhibitor, a prostacyclin-mimetic, a progestin, an oxytocin antagonist or a .beta.-agonist in an amount effective to ameliorate the symptoms thereof; and inadequate menses treated and induction of abortion or stimulation of labor in a pregnant female is achieved by uterine contractility stimulation by administering thereto a nitric oxide inhibitor, either alone or optionally in a combination of progesterone antagonist, an oxytocin or oxytocin analogue antagonist or a prostaglandin.

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 PGI.sub.2 -mimetic, a thromboxane (TXA.sub.2) inhibitor, a compound possessing TXA.sub.2 -agonistic and TXA.sub.2 -inhibiting properties, a compound possessing TXA.sub.2 -antagonistic and PGI.sub.2 -memetic activities, and a TXA.sub.2 antagonist.

Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.

Abstract: Aliphatic nitrate esters having a sulfur or phosphorus atom .beta. or .gamma. to a nitrate group and their congeners having efficacy as neuroprotective agents are described. Preferred nitrate esters may be synthesized by nitration of a 3-bromo-1,2-propanediol, and subsequent reaction to yield the desired mono-, di- or tetra-nitrate ester.

Abstract: New compounds and their compositions having anti-inflammatory, analgesic and anti-thrombotic activities, of the general formula: A--X.sub.1 --NO.sub.2 or their salts, wherein: A is R(COX.sub.u).sub.t, wherein t is zero or 1 and u is zero or 1; and X is O, NH or NR.sub.1C wherein R.sub.1C is C.sub.1 -C.sub.10 alkyl; and R is(Ia) wherein R.sub.1 is acetoxoy, preferably n ortho-position with respect to --CO-- and R.sub.2 is hydrogen; or derivatives of acetylsalylsalicyclic acid; and X.sub.1 is --YO-- wherein Y is C.sub.1 -C.sub.20 alkylene, C.sub.5 -C.sub.7 cycloalkylene, oxy-alkyl derivatives and oxy-methyl benzyl derivatives.

Abstract: The invention relates to new derivatives of acetylsalicylic acid (called ASA in the following), which contain an NO.sub.3 structure. They are therapeutically active either as the intact active compound molecule or after cleavage (NO release). The invention also relates to processes for their preparation and their use as medicaments, in particular for the alleviation of pain, inhibition of platelet aggregation, lowering of fever and for the prevention of cardiovascular disorders and oncoses.

Abstract: Aliphatic Nitrate esters having a sulfur or phosphorus atom .beta. or .gamma. to a nitrate group having efficacy as vasodilators are described. Preferred nitrate esters may be synthesized by nitration of a 3-bromo-1,2-propanediol, and subsequent reaction to yield the desired mono, di or tetra nitrate ester.

Abstract: A hydrophilic aqueous pump spray composition for treating angina pectoris comprising 0.15 to 0.50 weight/% of nitroglycerin, 24.50 to 24.85 weight/% of ethanol, 32.00 weight/% of 1,2-propyleneglycol and 43.00 weight/% of purified water and having a pH of 3 to 6; a method of producing the composition; and, a product comprising a container having the composition as a solution therein and provided with a dosage dispensing pump.

Abstract: An amino acid compound of the formula: R.sup.1 NH--CH(R.sup.2)--COHN--A--ONO.sub.2, wherein R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.7 alkanoyl group, a C.sub.1 -C.sub.6 alkoxycarbonyl group, a C.sub.6 -C.sub.10 arylcarbonyl group, a C.sub.7 -C.sub.13 aralkylcarbonyl group, a C.sub.7 -C.sub.13 aralkyloxycarbonyl group or a 5- or 6-membered aromatic heterocyclic carbonyl group; R.sup.2 represents a substituted C.sub.1 -C.sub.6 alkyl group; and A represents a C.sub.2 -C.sub.5 alkylene group; and pharmacologically acceptable salts thereof. The amino acid compound has an excellent vasodilator action for collateral vessels and is useful for treating angina pectoris.

Abstract: A stable, uniform, water-based topical cream containing nitroglycerin, a penetration enhancer, water, a thickener and an emulsifier is provided. Also provided are the method of preparing the cream and the use of the cream for treating male erectile dysfunction or female anorgasmia. The present invention also relates to treating patients suffering from microvascular diseases or from injured tissue.