Abstract: The present disclosure is directed to, inter alia, methods of treating a subject suffering from or diagnosed with depression, comprising administering to a subject in need of such treatment an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 to R4 are described herein and wherein the compound is administered prior to sleep.

Abstract: Disclosed herein are methods for treating conditions and/or disorders related to hyperglycemia. Such conditions and/or disorders related to hyperglycemia include, but are not limited to, type I, II diabetes mellitus, gestational diabetes, other forms diabetes, and disorders related thereto. In particular, the present invention relates to methods of using (R)-(+)-verapamil or a pharmaceutically acceptable salt thereof in the treatment of conditions and/or disorders related to hyperglycemia.

Abstract: The present invention relates generally to the use of compounds to treat a variety of disorders, diseases and pathologic conditions and more specifically to the use of substituted indol-5-ol derivatives to modulate protein kinases and for treating protein kinase-mediated diseases.

Abstract: The present invention relates to an industrially feasible and economically viable process for the preparation of fluvoxamine maleate of formula I.

Abstract: An object of the present invention is to develop a method of enhancing the cognitive ability of a brain to fundamentally cure a disease. It has been found out that, by using a medicament for treating or preventing a disease including a combination of a major tranquilizer, and vitamin C or a salt thereof and, if necessary, drip infusion, an antidepressant and an iron agent, the cognitive ability of a brain is enhanced, thus, an arbitrary disease including various cancers can be treated. The present invention also provides a method for treating or preventing a disease including a step of administering a major tranquilizer, and vitamin C or a salt thereof to a subject suffering from the disease.

Abstract: A method of treating a subject at risk of or suspected of having Fragile X syndrome or autism spectrum disorder associated with abnormalities of ERK includes administering to the subject a therapeutically effective amount of at least one ERK inhibiting compound that prevents abnormalities in neuronal connectivity, a prodrug thereof that is metabolisable to form the compound, or a pharmaceutically acceptable salt thereof.

Abstract: A composition, use of and a method of removing a hyperplastic skin lesion on a mammal comprising administering to the lesion or locus thereof a therapeutically effective amount of a composition comprising a blocker selected from the group consisting of a calcium channel blocker, a metabolite thereof, a calmodulin blocker and a metabolite thereof and a pharmaceutically acceptable diluent or carrier.

Abstract: A pharmaceutical composition for treating disorders associated with insulin resistance is disclosed, and the composition comprises at least one inhibitor which is an effective agent to suppress endothelin-1-stimulated resistin gene expression through decreasing the endothelin-1-stimulated phosphorylation of proteins downstream of endothelin type A receptor, wherein the downstream signaling molecules comprise ERK1/2, JNKs, AKT, and STAT3 proteins, and wherein the inhibitor is selected from at least one antagonist of the endothelin type A receptor or downstream signaling proteins.

Abstract: Disclosed are compounds of formulae (I), (III), (IV), (VII), (X), (XI), (XII), (XIII) and (XIV), wherein the variables are as defined in the claims, and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: Compounds of formula (I) wherein the symbols have the meaning given in the specification, as well as processes for preparing the compounds (I), pesticidal compositions and synergistic mixtures comprising compounds (I), methods for the control of insects, acarids or nematodes by contacting the pests or their food supply, habitat or breeding grounds with a pesticidally effective amount of compounds formula (I), and a method for treating, controlling, preventing or protecting animals against infestation or infection by parasites which comprises orally, topically or parenterally administering or applying to the animals a parasiticidally effective amount of compounds of formula (I).

Abstract: The invention relates to a dosage form comprising a physiologically effective amount of a physiologically active substance (A), a synthetic, semi-synthetic or natural polymer (C), optionally one or more physiologically acceptable auxiliary substances (B) and optionally a synthetic, semi-synthetic or natural wax (D), wherein the dosage form exhibits a resistance to crushing of at least 400 N and wherein under physiological conditions the release of the physiologically active substance (A) from the dosage form is at least partially delayed.

Abstract: Anti-cancer compositions and methods are described herein. In particular, compositions including one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described. Methods for treatment of pathological conditions particularly cancer, in a subject using one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described herein.

Abstract: A drug delivery system for sustained delivery of bioactive agents, the system includes a matrix including nanofibrillated cellulose derived from plant based material and at least one bioactive agent, and at least one support selected from synthetic polymers, bio compounds and natural polymers. Also, methods for the manufacture of the system and methods of using it.

Abstract: The invention relates to a liquid vehicle that can be used to create suspensions and/or solutions of liquid or powdered medications. The vehicle is thixotropic and has improved stability and rheologic characteristics. Vehicles of the invention include an aqueous medium and a suspending agent comprising a polysaccharide having at least 50% glucose repeating saccharide units and at least 90% alpha linkages. The polysaccharide can be a starch, modified starch, or glycogen. The aqueous medium and individual components of the vehicle provide a palatable and easily ingested drug preparation. The invention also provides a vehicle containing an aqueous medium, suspending agent comprising a polysaccharide having at least 50% glucose repeating saccharide units and at least 90% alpha linkages, buffer, and artificial sweetener, the combined suspending vehicle having a pH of about 3 to about 10 and an osmolality of 300 mOmsol or less.

Abstract: A pharmaceutically delivery system is described comprising a pharmaceutically active agent and acidified nitrite as an agent to produce local production of nitric oxide at the skin surface. The dosage form may be in any pharmaceutically acceptable carrier means and comprises an acidifying agent adapted to reduce the pH at the environment. In one embodiment, a barrier consisting of a membrane allows diffusions of the anaesthetic and nitrite ions while preventing direct contact of the skin and acidifying agent.

Abstract: Compositions and method for stimulating and controlling arteriogenesis and lymphatic vasculature by preventing and/or reducing the cellular interaction between RAF1 and AKT have been developed. The compositions include molecules that increase the bioavailability of non-phosphorylated RAF1, for example, the RAF1 Ser259 to Ala259 mutant in (RAF1 S259A), and AKT1 inhibitory molecules. Defects, disorders or diseases of insufficient blood or lymphatic vasculature are treated by administering to a patient in need thereof, a pharmaceutical composition comprising a molecule specifically blocking RAF1-AKT crosstalk in a pharmaceutically acceptable carrier or excipient in an amount effective to enhance the growth of blood or lymphatic vasculature in the patient.

Abstract: The present invention relates to compositions for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery composition for delivering a drug having potential for dose dumping in alcohol, related methods of preparing these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compositions to the patient. Most preferably, the dosage form includes verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding.

Abstract: The present invention relates to controlled porous osmotic pump tablets of high permeable drugs and the preparation process thereof. The controlled porosity osmotic pump tablets do not need to be drilled by laser, but provides controlled porosity for drug release by adding a suitable quantity of pore-forming agents into the semipermeable membrane. In specific embodiments, the present invention relates to controlled porous osmotic pump tablets comprising venlafaxine or metoprolol or pharmaceutically acceptable salts thereof.

Abstract: The invention relates to a dosage form comprising a physiologically effective amount of a physiologically active substance (A), a synthetic, semi-synthetic or natural polymer (C), optionally one or more physiologically acceptable auxiliary substances (B) and optionally a synthetic, semi-synthetic or natural wax (D), wherein the dosage form exhibits a resistance to crushing of at least 400 N and wherein under physiological conditions the release of the physiologically active substance (A) from the dosage form is at least partially delayed.

Abstract: This disclosure relates to compounds and compositions for forming bone and methods related thereto. In certain embodiments, the disclosure relates to methods of forming bone comprising implanting a bone graft composition comprising a growth factor such as BMP in a subject at a site of desired bone growth or enhancement in combination with a JAB1 blocker.

Abstract: The present invention provides methods for the prevention, treatment and/or amelioration of fibrosis or fibrotic conditions. The present invention further provides small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling to prevent, treat and/or ameliorate fibrosis or fibrotic conditions. Kits comprising small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling and methods of identifying small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling are also provided.

Abstract: A method and composition for treating osteoarthritis with ion-channel regulators is disclosed. The ion-channel regulators are used alone or in combination with other osteoarthritis treatment agents, including but not limited to injectable agents such as viscosupplements and steroids. A composition comprising one or more ion-channel regulator(s) and one or more osteoarthritis treatment agent(s) is also disclosed.

Abstract: Disclosed herein are methods and composition for treating a disease or condition related to orexin receptor 1, orexin receptor 2, somatostatin receptor 2 or dopamine D2L receptor. The method comprises administering a composition comprising an effective amount of verapamil and a pharmaceutically acceptable excipient to a subject, wherein the verapamil is capable of binding to at least one of a receptor selected from the group consisting of orexin receptor 1, orexin receptor 2, somatostatin receptor 2 and dopamine D2L receptor of the subject.

Abstract: The present invention relates to, among other things, methods for treating trigeminal cephalgias such as migraine and migraine like headaches and other cerebrovascular conditions associated with pain and or inflammation. When non-steroidal anti inflammatory drugs (NSAIDs), such as ketoprofen, are applied locally using specific topical formulations immediate relief of pain is obtained. Intense pain is typically reduced to mild pain or no pain within 30 minutes of application of the topical formulation. The NSAID may be given in combination with other pharmacological agents, such as vasoconstrictors, opioids, decongestants and/or non-opioid migraine drugs, such as triptans and ergots and agents that affect serotonin receptors as agonists, antagonists or partial agonists.

Abstract: A liposome including a lipid bilayer, an elastin-like polypeptide (ELP) conjugated to a hydrophobic moiety; a chemosensitizer; and an anticancer agent, a pharmaceutical composition including the same, and a method of delivering a chemosensitizer and an anticancer agent to a target site of a subject by using the liposome.

Abstract: Methods described herein relate to mitochondria and their role in Human immunodeficiency virus type 1 (HIV-1) infection and cell-to-cell HIV-1 transmission and compositions and methods for modulating mitochondrial mediated cell-to-cell transmission of HIV-1. Methods for screening to identify inhibitors of mitochondrial mediated cell-to-cell transmission of HIV-1 are also envisioned herein.

Abstract: The present invention provides methods of killing, inhibiting the growth, and/or inhibiting the reproduction of kinetoplastid or apicomplexan protozoan with tyrosine kinase inhibitors.

Abstract: A solid dosage form suitable for forming a tablet for the containment and delivery of medicament is provided wherein the matrix forming material is a pressure sensitive adhesive, present in the amount from about 0.1 to about 40 weight %, based on the total weight of the composition. The dosage form is comprised of the medicament and a water-insoluble polymer silicone pressure sensitive adhesive and allows release of the medicament in a controlled fashion depending on simple parameters such as weight percent of the polymer silicone adhesive. A sustained release dosage form is provided for delivery of medicament wherein the release rate of medicament does not depend on the dissolution medium of the pH. Another aspect of invention is formation of solid tablets of poorly compressible material and the method for making the solid composition. The dosage form for this invention s particularly suitable for oral dosage forms.

Abstract: The present invention relates to the treatment and prevention of vasospasm. The present invention provides a system for treating a cerebral vasospasm in a human utilizing a pharmaceutical composition and administrating a therapeutically effective amount of the pharmaceutical composition to a predetermined location in close proximity to a cerebral artery within a subarachnoid space wherein the pharmaceutical composition produces a localized pharmacologic effect thereby treating the cerebral vasospasm.

Abstract: In one aspect, the present invention is concerned with a treatment where it is desired that an active agent is designed to be released in a prolonged manner at a time point some time after administration of the active agent. The present invention is particularly suited to administering an agent which may be released whilst a subject is sleeping, shortly before waking and continues to administer the drug during the early waking hours. As well as treating certain conditions by a particular regime, the invention also provides novel formulations for a delayed, followed by a prolonged release of drug.

Abstract: Disclosed are nitrile derivatives and pharmaceutical compositions comprising nitrile derivatives. The pharmaceutical compositions comprise compounds of the formula I and the pharmaceutically acceptable salts of such compounds. Also disclosed are processes for the preparation of such compounds, intermediates used in the preparation of such compounds, and the uses of such compounds in treating hyperproliferative diseases, inflammatory diseases and viral and bacterial infections and inducing apoptosis in cancer cells.

Abstract: The present invention relates to the field of therapeutic methods to screen for compounds on the basis of their ability to influence Wnt activity. The screening process is applied to both a physical library of a series of compounds and a virtual library of compounds that affect Wnt activity. In one aspect, the virtual screening process could be carried out where a permutational library of small peptides is substituted for the small organic molecules. The inventive methods may be used to empirically test for effects on Wnt activity and may also be applied to any pair of proteins involved in protein-protein interactions.

Abstract: The present invention relates to biphenyl-based renin inhibitor compounds having amino-terminal groups, and their use in treating cardiovascular events and renal insufficiency.

Abstract: A method and composition for treating osteoarthritis with ion-channel regulators is disclosed. The ion-channel regulators are used alone or in combination with other osteoarthritis treatment agents, including but not limited to injectable agents such as viscosupplements and steroids. A composition comprising one or more ion-channel regulator(s) and one or more osteoarthritis treatment agent(s) is also disclosed.

Abstract: A method and composition for treating osteoarthritis with ion-channel regulators is disclosed. The ion-channel regulators are used alone or in combination with other osteoarthritis treatment agents, including but not limited to injectable agents such as viscosupplements and steroids. A composition comprising one or more ion-channel regulator(s) and one or more osteoarthritis treatment agent(s) is also disclosed.

Abstract: This invention relates to the field of biologically active compounds and specifically to closthioamides, pharmaceutical compositions comprising these compounds, and their use as antibiotic, antifungal, and/or cytotoxic agent.

Abstract: In the broadest aspect, the invention provides a composition for and a method of prophylactic and/or therapeutic treatment of a animal/mammal for any viral disease, mixed bacterial and viral infections, bacterial infections, bacterial endotoxins, bacterial exotoxins, autoimmune diseases, and cellular or humoral mediated allergic conditions that is caused by any virus that relies on the maintenance of specific calcium ion concentrations for the post ribosomal RNA synthesis processing of viral protein translation, transportation and processing of viral structural components by utilizing a therapeutic amount of a blocker selected from the group consisting of a calcium channel blocker, a metabolite thereof, a calmodulin blocker and a metabolite thereof, and a pharmaceutical acceptable diluent or carrier; and/or is caused by damage to the animal/mammal by a pathological immune response to antigens.

Abstract: The invention relates to the use of at least on inhibitor selected from the group consisting of raf-, protein kinase C (PKC)-, MEK1/2-, or ERK1/2-inhibitors, for the manufacturing of a medicament to be administrated from 1 up to 12 hours after initiation of an ischemic disease.

Abstract: Methods for concomitant administration of colchicine together with one or more second active agents, e.g., verapamil, are disclosed. Such methods reduce the dangers commonly associated with such concomitant administration and provide additional benefits. Methods of notifying health care practitioners and patients regarding appropriate dosing for concomitant administration of colchicine together with second active agents are also provided.

Abstract: A process for preparing pellets by high shear granulation containing a pharmaceutical active ingredient with a pH dependent water solubility, the pellets obtained with said process and pharmaceutical oral dosage forms comprising said pellets.

Abstract: Disclosed are nitrile derivatives and pharmaceutical compositions comprising nitrile derivatives. The pharmaceutical compositions comprise compounds of the formula I and the pharmaceutically acceptable salts of such compounds. Also disclosed are processes for the preparation of such compounds, intermediates used in the preparation of such compounds, and the uses of such compounds in treating hyperproliferative diseases, inflammatory diseases and viral and bacterial infections and inducing apoptosis in cancer cells.

Abstract: The invention provides compounds, compositions, methods, and kits for the treatment of neurogenic inflammation.

Abstract: A pH dependent drug delivery system comprising a pH sensitive graft copolymer, a therapeutically active agent and other pharmaceutically acceptable ingredients. More specifically, a composition which is capable of suppressing the drug release in the acidic pH prevalent in the stomach and releasing the drug over an extended period of time at pH prevalent in the intestinal region.

Abstract: Novel derivatives of ?-cyano-?-naphthyl acrylates, sunscreen compositions including one or more ?-cyano-?-naphthyl acrylate derivatives are described herein. Also disclosed are methods for stabilizing a sunscreen composition and methods of filtering out ultra-violet light from a substrate by the addition of one or more of the foregoing ?-cyano-?-naphthyl acrylate derivatives.

Abstract: The present invention provides new tyrphostin derivatives acting as protein tyrosine kinase (PTK) inhibitors and receptor tyrosine kinase (RTK) inhibitors, and/or which directly or indirectly affect proteins in the PTK-mediated signal transduction pathway, methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for preventions and treatments of PTK and RTK related disorders such as metabolic, fibrotic, and cell proliferative disorders, in particular psoriasis and cancer.

Abstract: The present disclosure relates to the regulation and function of the Wnt/?-catenin signaling pathway and the ERK signaling pathway. The disclosure provides methods of treatment for melanoma by administering both an inhibitor of ERK signaling and an activator of Wnt/?-catenin signaling. These methods may be used alone or in combination with other strategies targeting melanoma cell survival. The disclosure also provides diagnostic methods for predicting a patient's clinical response to inhibitors of ERK signaling.

Abstract: Disclosed are compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically related to GPR35, and/or GPR35-hERG signaling complex. For example, disclosed are compounds for preventing and/or treating diseases which are pathophysiologically related to GPR35 in a subject.

Abstract: A composition, use of and a method of removing a hyperplastic skin lesion on a mammal comprising administering to the lesion or locus thereof a therapeutically effective amount of a composition comprising a blocker selected from the group consisting of a calcium channel blocker, a metabolite thereof, a calmodulin blocker and a metabolite thereof and a pharmaceutically acceptable diluent or carrier.

Abstract: The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.

Abstract: The present invention relates to biphenyl-based renin inhibitor compounds having amino-terminal groups, and their use in treating cardiovascular events and renal insufficiency.