Abstract: Methods for treating a demyelinating condition in a subject in need of treatment are provided. In some aspects the methods encompass administering to the subject an amount of a Ca2+-channel blocker effective to treat the demyelinating condition. In other aspects, the methods encompass administering to the subject an amount of a glutamate inhibitor effective to treat the demyelinating condition. In additional aspects, the methods encompass administering to the subject a Ca2+-channel blocker in combination with a glutamate inhibitor, in amounts effective to treat the demyelinating condition. In still other aspects, the methods encompass administering to the subject a Ca2+-channel blocker in combination with a hypertensive agent, in amounts effective to treat the demyelinating condition. Also provided are pharmaceutical compositions having a Ca2+-channel blocker, a glutamate inhibitor, and a pharmaceutically-acceptable carrier.

Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and an antihypertensive agent, a prodrug thereof or a pharmaceutically acceptable salt of said antihypertensive agent or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy.

Abstract: The present invention comprises methods and compositions for use in inhibiting egg production by parasitic trematode worms comprising administering to an individual in need thereof an effective amount of an agent which transiently inhibits the influx of calcium through a cell membrane calcium channel. Inhibition of egg production in the worms ameliorates many of the symptoms and pathology related to infection by trematode related diseases, including Schistosomiasis. The methods can also effect disease transmission by reducing the number of eggs released into the environment available to continue the worm life cycle.

Abstract: The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing lidocaine, verapamil, diltiazem, isometheptene, or lisuride that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of lidocaine, verapamil, diltiazem, isometheptene, or lisuride. In a method aspect of the present invention, one of lidocaine, verapamil, diltiazem, isometheptene, or lisuride is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of lidocaine, verapamil, diltiazem, isometheptene, or lisuride, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal.

Abstract: Compounds of formula (I) are antibacterial agents wherein: R3 and R4, taken together with the carbon atoms to which they are respectively attached, form an optionally substituted saturated carbocyclic or heterocyclic ring of 5 to 16 atoms, which may be benz-fused or fused to a second optionally substituted saturated carbocyclic or heterocyclic ring of 5 to 16 atoms; and R1 and R2 are as defined in the specification.

Abstract: A once-a-day controlled release drug delivery system of diltiazem hydrochloride is provided, which is bioequivalent in plasma profile of Cardizem CD. The fast, medium, and slow release fractions are prepared using various compositions and weight gains. The individual fill weights are computed and then are filled into the same capsule using specialized encapsulation equipment using a triple-filling process. A preferred membrane dispersion that is used for preparing the fast release fraction contains 0.2% of sodium lauryl sulfate along with 20% of water soluble plasticizer (triethyl citrate), and 2% silicone dioxide, based on quaternary polymethacrylate on the weight basis. This combination provides an initial pulsatile burst after a lag time of 2 hours, leading to in-vivo bioequivalence. The preferred membrane dispersion that is used for preparing the medium release and the slow release fractions contain 16% of water soluble plasticizer along with 5% silicone dioxide, based on quaternary polymethacrylate.

Abstract: Novel forms of sustained-release microgranules (LP) containing diltiazem are disclosed. The microgranules consist of a neutral granular carrier coated with an active layer including diltiazem or a pharmaceutically acceptable salt thereof as the active principle, a surfactant and a binder, and an outer layer providing sustained release of the active principle (layer LP).

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: Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: The invention is of a non-invasive, topical medicament and associated methodology for use thereof, through the use of which existing scars may be effectively, cost effectively, and painlessly treated. One or more calcium channel blocker agents serve as the primary active ingredient of the present compositions and transdermal penetration agents or carriers are included to facilitate topical delivery of the active ingredient(s) to the intended, sub-dermal treatment site.

Abstract: The invention is of a topical medicament and associated methodology for use thereof, through the use of which sub-dermal, aberrant fibrotic tissue masses are “remodeled” through the topical, non-invasive, transdermal application of the calcium channel blocker diltiazem.

Abstract: Methods for the simple, reliable application and local controlled release of selected anti-arrhythmia drugs from a hydrogel applied to or polymerized on the tissues of the heart or its vessels, especially in conjunction with cardiac bypass or other cardiac surgery, have been developed. The anti-arrhythmia drugs are incorporated into hydrogels that biodegrade and adhere to the tissues to which the anti-arrhythmic drugs are to be delivered. The hydrogels may be formed in vitro or in vivo. In a preferred embodiment, the drugs are effective to lengthen atrial effective refractory period. A particularly preferred drug is amiodarone.

Abstract: The invention is of a topical medicament and associated methodology for use thereof, through the use of which fibrosis of the elastic tissues and muscles of the human penis is reduced, thereby improving erectile function and/or reversing erectile dysfunction. One or more calcium channel blocker agents serve as the primary active ingredient of the present compositions, with carrier agents facilitating non-invasive transdermal delivery of the calcium channel blocker(s) to fibrotic tissues of the penis.

Abstract: A sustained release pharmaceutical formulation is disclosed. The formulation comprises a water soluble medicament and a polymer mixture comprising a first component of about 80 weight percent polyvinylacetate combined with about 20 weight percent polyvinyl pyrrolidone, of the total weight of the first component, combined with a second component of a cellulose ether polymer.

Abstract: The present invention comprises methods and compositions for use in inhibiting egg production by parasitic trematode worms comprising administering to an individual in need thereof an effective amount of an agent which transiently inhibits the influx of calcium through a cell membrane calcium channel. Inhibition of egg production in the worms ameliorates many of the symptoms and pathology related to infection by trematode related diseases, including Schistosomiasis. The methods can also effect disease transmission by reducing the number of eggs released into the environment available to continue the worm life cycle.

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 pharmaceutical combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents, kits containing such combinations and methods of using such combinations to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. This invention also relates to additive and synergistic combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents whereby those synergistic combinations are useful in treating subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and those subjects presenting with symptoms of cardiac risk, including humans.

Abstract: The present invention relates to compounds of formula I, 1

Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and an antihypertensive agent, a prodrug thereof or a pharmaceutically acceptable salt of said antihypertensive agent or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy.

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 regime or regimen for loosening/slackening and/or relaxing cutaneous and/or subcutaneous human skin tissue, advantageously for cosmetically/therapeutically treating skin wrinkles and fine lines, comprises administering to a candidate subject in need of such treatment, a thus-effective amount of at least one inhibitor of at least one calcium channel.

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 invention is of a novel, noninvasive method for treating cellulite involving the topical application of one or more calcium channel blocker agents suspended in one or more carriers with penetration enhancing agent's to effect transdermal delivery of the calcium channel blocker agent(s). Periodic, topical application of the medicaments taught here in will effect, usually within a few months, a substantial reduction or elimination of palpable cellulite.

Abstract: A pharmaceutical composition comprising as its active ingredients one or more drugs selected from the group consisting of angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, and one or more insulin resistance improving agents exhibits excellent arteriosclerotic progress inhibitory effects, and is useful as a drug, particularly as a drug for the prevention or treatment of arteriosclerosis. The invention also provides a method for the treatment or prophylaxis of arteriosclerosis by administering in combination (i) at least one of said angiotensin II receptor antagonists or angiotensin converting enzyme inhibitors and (ii) one or more insulin resistance improving agents to a mammal suffering from or susceptible to arteriosclerosis.

Abstract: The present invention provides an osmotic device containing controlled release diltiazem in the core in combination with a rapid release ACE inhibitor, or diuretic, in an external coat. The delivery device of the invention can also be a chronotherapeutic osmotic device that provides a delayed and controlled release of diltiazem and a delay and rapid release of an ACE inhibitor or diuretic. A wide range of ACE inhibitors or diuretics can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. One specific embodiment of the osmotic device includes an external coat that has been spray coated rather than compression coated onto the device. The device with spray coated external core is smaller and easier to swallow than the similar device having a compression coated external coat. The device is useful for the treatment of blood pressure or hypertension related disorders.

Abstract: A method of treating hyperproliferation diseases in mammals in need of such treatment which method includes administering to said mammal a therapeutically effective amount of a compound of the formula: or a pharmaceutically acceptable salt, hydrate or prodrug thereof, wherein R1, R2, R3, R4, W, X, Y, Z and t are as defined herein.

Abstract: A method of treating pulmonary hypertension in a subject in need of such treatment comprises inhibiting EMAP II activity in the subject by an amount effective to treat the pulmonary hypertension in the subject (e.g., in the lungs and more particularly in the pulmonary vasculature). Pharmaceutical formulations useful for carrying out such methods (e.g., an antibody that specifically binds to EMAP II in a pharmaceutically acceptable carrier) and screening techniques useful for identifying additional compounds that can be used for carrying out such methods are also disclosed.

Abstract: This invention provides a method of treating an animal with pyrophosphate gout or osteoarthritis comprising administering an effective amount of a calcium antagonist, thereby reducing calcium pyrophosphate crystal deposition in the animal.