Abstract: The invention relates to the isolation or extraction of exosomes.

Abstract: A method is provided to prevent and to treat Macular Degeneration by using Calcium Channel Blockers, Angiotensin-Converting Enzyme (ACE) Inhibitors, or Angiotensin Receptor Blockers (ARB), and more particularly, to a method to prevent and treat Macular Degeneration by using Calcium Channel Blockers, Angiotensin-Converting Enzyme Inhibitors, or Angiotensin Receptor Blockers that are not taken orally, but administered by ophthalmic preparation directly onto or into the eye where Macular Degeneration is formed, to increase the capillary network and blood supply to the retinal macula.

Abstract: A method of preventing or treating a subject suffering from a flavivirus infection by administering an effective amount of berbamine or its analogue to the subject, berbamine has a structure of Formula (I), wherein the flavivirus infection is caused by Japanese encephalitis virus, Zika virus or Dengue virus. A method of inhibiting the entry of a flavivirus, an enterovirus and/or a lentivirus into host cells includes contacting the host cells with an effective amount of berbamine of its analogue, berbamine has a structure of Formula (I), wherein the flavivirus is Japanese encephalitis virus, Zika virus or Dengue virus.

Abstract: This disclosure provides methods for the treatment of disease by administering pharmaceutical compounds. In particular, the disclosure relates to the treatment to improve memory or cognition, or to treat a memory or cognitive disorder, or to treat cognitive symptoms of a disease or condition by administering a T-type calcium channel antagonist.

Abstract: A method of preventing COVID-19 infection in an individual, the method comprising the steps of providing an individual that is not infected with COVID-19; administering four antimicrobials to the individual, wherein the antimicrobials comprise: hydroxychloroquine; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19. A method of treating an individual infected with COVID-19, the method comprising the steps of: providing an individual infected with COVID-19; administering five antimicrobials to the individual, wherein the antimicrobials comprise: hydroxychloroquine; azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

Abstract: A method of treating an individual infected with COVID-19, the method comprising the steps of: providing an individual infected with COVID-19; administering five antimicrobials to the individual, wherein the antimicrobials comprise: hydroxychloroquine; azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

Abstract: A method for healing a hard-to-heal wound including the steps of: topically administering a wound healing composition to a wounded area, wherein the wound healing composition includes, at least one of: (a) a medicament characterized as a calcium channel blocker or pharmaceutically acceptable salts or solvates thereof; (b) a medicament characterized as an alpha-adrenergic antagonist or pharmaceutically acceptable salts or solvates thereof; (c) a medicament characterized as a direct vasodilator or pharmaceutically acceptable salts or solvates thereof; and (d) a medicament characterized as a phosphodiesterase type five inhibitor or pharmaceutically acceptable salts or solvates thereof; and (e) a hemorrheologic agent or pharmaceutically acceptable salts or solvates thereof; (f) a primary dermal penetrating agent or pharmaceutically acceptable salts or solvates thereof: and (g) a topical stimulating agent or pharmaceutically acceptable salts or solvates thereof.

Abstract: A composition of botulinum toxin is claimed which can penetrate into the ocular surface inclusive of a penetration through a conjunctiva, cornea, and other structures. This composition allows for a maximal penetration of a topical preparation of botulinum toxin which serves to reduce the need for frequent allergy drops for the treatment of ocular surface disease and other conditions causing ocular surface inflammation or deep ocular inflammation. No puncture of the needle is necessary for the administration. Herein describes a novel composition using several principles based on composition, method of application, which enhances the effectiveness of the penetration.

Abstract: Methods are provided for treating conditions including chronic pelvic pain, in which there are palpable trigger points of local areas of muscle restriction and spasticity that recreate or refer pain of patients complaints upon palpation, chronic pelvic pain syndrome, pelvic floor myalgia, pelvic floor dysfunction, interstitial cystitis, levator ani syndrome, coccygodynia, prostatodynia, piriformis syndrome, anal sphincter pain, bowel movement pain, post bowel movement pain, ejaculatory pain, post ejaculatory pain, sitting pain, post bowel movement pain, rectal pain, tailbone pain, urinary frequency, urinary urgency, urinary hesitancy, post urinary pain, overactive bladder, perineal pain, penile pain, vaginismus, anismus, sexual dysfunction, reduced level of ejaculate or reduced penile erection, myofascial pain in muscle tissue of a patient who has one or more trigger points in the muscle tissue, or the pain/sensitivity of pelvic floor muscle trigger points and specific areas of myofascial restriction detected

Abstract: Disclosed are non-ionic surfactant vesicle formulations of calcium channel blockers, such as diltiazem, and methods of using the formulations for treating anal disorders.

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 invention relates to extended release dosage forms of metoprolol or salts thereof comprising a water insoluble and non-swellable inert core and one or more pharmaceutically acceptable excipients. The invention also relates to processes for the preparation of an inert core and extended release dosage forms.

Abstract: Controlled release preparations and soft capsules are provided. Also provided are emulsions and suspensions, including compositions and methods of manufacturing controlled release soft capsules, where the fill contains a suspension and/or an emulsion.

Abstract: Cosmetic skin and hair care compositions for enhancing the growth and appearance of mammalian hair in an individual are provided, which compositions comprise a dose of an L-type calcium channel blocker effective to promote anagen phase of the hair cycle. As shown herein, anagen phase promotion can result in more rapid hair growth.

Abstract: To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating.

Abstract: The present invention discloses method to treat infections caused by filovirus. Such a method comprises blocking the PI3 kinase pathway or the calcium-associated pathway at the gene or protein level. Also disclosed herein are the compounds useful in the treatment of filoviral infection.

Abstract: A method and composition are provided for the treatment of an anorectal disorder and for controlling the pain associated therewith. The method comprises administering to a subject in need of such treatment therapeutically effective amounts of a calcium channel blocker either alone or together with a nitric oxide donor. Amlodipine, anipamil, barnidipine, benidipine, bepridil, darodipine, diltiazem, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, lidoflazine, manidipine, mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tiapamil, verapamil and pharmaceutically acceptable salts thereof, are suitable calcium channel blockers.

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: The present invention relates to new biphenyl-3-carboxylic acid modulators of beta-3-adrenoceptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Disclosed are sustained release oral solid dosage forms comprising a therapeutically effective amount of a medicament having a solubility of more than about 10 g/l; a pH modifying agent; and a sustained release matrix comprising a gelling agent, said gelling agent comprising a heteropolysaccharide gum and a homopolysaccharide gum capable of cross-linking said heteropolysaccharide gum when exposed to an environmental fluid, said dosage form providing a sustained release of said medicament after oral administration to human patients.

Abstract: Compositions and methods for treating systemic diseases by intravenous administration of formulations of synthesized curcumin (diferuloylmethane) and concomitantly a calcium channel blocker to human subjects with neoplastic and neurodegenerative diseases are disclosed herein. The diseases are treated by prolonged administration of sub-optimal doses of liposomal curcumin or polymeric nanocurcumin or the sustained release curcumin from PLGA nanocurcumin at dosages below systemic hemolytic thresholds concomitantly with or without calcium channel blockers.

Abstract: A method for determining the risk, severity or progression of cardiovascular disease, such as cardiac heart failure. A method for determining the likelihood of admission to the hospital for cardiac heart failure. The methods include determining the concentration of ET-1 and the concentration of one or more of biomarkers selected from the group consisting of cardiac troponin (e.g., cTnI, cTnT), VEGF, BNP, NT-proBNP, and IL-6 in a blood, serum or plasma sample from the patient.

Abstract: The invention relates to compositions, methods, and kits for treating subjects infected by or at risk of infection with a DNA virus (e.g., a JC Virus or a BK virus). Aspects of the invention are useful to prevent or treat DNA virus associated conditions (e.g., PML) in subjects that are immunocompromised. Compositions are provided that inhibit intracellular replication of DNA viruses.

Abstract: A controlled release diltiazem dosage formulation comprising a plurality of diltiazem pellets and a gel-forming material where the time of maximum diltiazem blood plasma levels occurs more than 8 hours after administration and preferably more than 10 hours after administration.

Abstract: There is provided compositions and methods for the treatment of respiratory conditions such as pulmonary hypertension and sickle-cell disease in a patient in need thereof. The composition and method are for treating a patient in need thereof by inhalation of a composition containing amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutical 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: Disclosed herein are compositions that are useful in effecting the transdermal delivery of therapeutic agents. More particularly, the disclosed transdermal compositions may include a fatty alcohol (for example, octanol), a terpene (for example, limonene), and an active agent comprising an amine moiety.

Abstract: The present invention provides methods and compositions for modulating certain metabolic processes and for treating a variety of disorders associated with metabolic syndrome, including insulin related disorders, ischemia, oxidative stress, atherosclerosis, hypertension, obesity, abnormal lipid metabolism, and stroke by administering an effective dose of a chloroquine compound. The invention also provides methods and compositions relating to administering an effective dose of a chloroquine compound in combination with at least a second pharmaceutically active ingredient or compound including an antihyperglycemic diabetes treatment, an antihypertensive agent, an antithrombotic agent, and/or an inhibitor of cholesterol synthesis or absorption.

Abstract: The present invention relates to the prevention of cardiovascular and central nervous system side effects in mammals who receive transfusions of hemoglobin based oxygen carriers (HBOC) or stored blood products containing a concentration of hemoglobin sufficient to induce vasoconstriction, by adding a vasoactivity reducing effective amount of one or more phosphodiesterase inhibitors in combination with a calcium channel blocker and/or an alpha agonist, to the circulation, or alternatively to the HBOC or stored blood, thereby preventing the manifestation of vasoactivity attributable to the presence of free tetrameric hemoglobin (Hb).

Abstract: Provided herein are methods and compositions for the treatment of motor neuron diseases including, for example, amyotrophic lateral sclerosis. Suitable therapeutic agents include, for example, agents that up-regulate the expression IGF-II or guanine deaminase in a cell.

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: The present invention relates to the use of a substance with the core structure of formula (I), or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the manufacture of a composition for the treatment of insulin resistance or diseases associated with insulin resistance, preferably in human subject in a daily dosage in a range of from about 5 mg to about 1500 mg. The invention furthermore relates to a method of treating insulin resistance or diseases associated with insulin resistance in a mammal, said method comprises administering to said mamma, preferably a human subject, a substance with the core structure of formula (I), preferably in a daily dosage in a range from about 5 mg to about 1500 mg. The substance is preferably isosteviol or steviol, or pharmaceutically acceptable salts, solvates or prodrugs thereof. Examples of diseases associated with insulin resistance and e.g.

Abstract: The present invention relates to short-acting calcium channel blocking compounds and their use to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension in general, hypertension been.) fore, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

Abstract: The invention relates to compositions, methods, and kits for treating subjects infected by or at risk of infection with a DNA virus (e.g., a JC Virus or a BK virus). Aspects of the invention are useful to prevent or treat DNA virus associated conditions (e.g., PML) in subjects that are immunocompromised. Compositions are provided that inhibit intracellular replication of DNA viruses.

Abstract: A buccal delivery system is disclosed suitable for delivery of a therapeutic agent to the oral cavity of a patient. The delivery system comprises a matrix for containing and releasing the therapeutic agent into the oral cavity and an alkyl N,N-disubstituted amino acetate in said matrix. A particularly preferred delivery system comprises a matrix containing an effective amount of therapeutic agent together with an alkyl N,N-disubstituted amino acetate, such as dodecyl 2-(N,N-dimethylamino) propionate salt.

Abstract: Preferred embodiments of the present invention are related to novel therapeutic drug combinations and methods for treating and/or preventing pulmonary arterial hypertension and/or stable angina. More particularly, aspects of the present invention are related to therapeutic combinations comprising a Rho-kinase inhibitor, such as fasudil, and one or more additional compounds selected from the group consisting of prostacyclins, such as iloprost, endothelin receptor antagonists, PDE inhibitors, calcium channel blockers, 5-HT2A antagonists, such as sarpogrelate, selective serotonin reuptake inhibitors, such as fluoxetine, statins, and vascular remodeling modulators, such as Gleevec.

Abstract: The invention provides a method of manufacturing a patch preparation comprising (a) pouring a composition for forming an adhesive layer into a container having a concave part with a shape corresponding to a patch preparation to be manufactured, wherein the composition contains a drug, an adhesive polymer, and an organic solvent; (b) removing the organic solvent from the composition through drying to form a drug-containing adhesive layer in the concave part; and (c) laminating a support on the drug-containing adhesive layer to provide the patch preparation comprising a support and the drug-containing adhesive layer formed on one surface of the support.

Abstract: A method and composition are provided for the treatment of an anorectal disorder and for controlling the pain associated therewith. The method comprises administering to a subject in need of such treatment therapeutically effective amounts of a calcium channel blocker either alone or together with a nitric oxide donor. Amlodipine, anipamil, barnidipine, benidipine, bepridil, darodipine, diltiazem, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, lidoflazine, manidipine, mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tiapamil, verapamil and pharmaceutically acceptable salts thereof, are suitable calcium channel blockers.

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: The present invention relates to new crystalline polymorphs of 6-(Piperidin-4-yloxy)-2H-isoquinolin-1-one hydrochloride, processes for their preparation and their use, in particular for the preparation of medicaments.

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 composition and method for the treatment of degenerative joint disease is disclosed. The composition includes a combination of a first ion-channel regulator, at least a second ion-channel regulator, and a pharmaceutically acceptable carrier suitable for intraarticular injection. Methods and kits for treating a degenerative joint disease are also disclosed.

Abstract: A method and composition are provided for the treatment of an anorectal disorder and for controlling the pain associated therewith. The method comprises administering to a subject in need of such treatment therapeutically effective amounts of a calcium channel blocker either alone or together with a nitric oxide donor. Amlodipine, anipamil, barnidipine, benidipine, bepridil, darodipine, diltiazem, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, lidoflazine, manidipine, mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tiapamil, verapamil and pharmaceutically acceptable salts thereof, are suitable calcium channel blockers.

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: Compositions and methods for treating type 2 diabetes and its sequelae by intravenous or subcutaneous administration of formulations of synthesized curcumin (diferuloylmethane) and concomitantly one or more anti-diabetic agents to human subjects are disclosed herein. The composition of the present invention may be used to: (i) treat patients with diabetes in advanced stages with evidence of any or all encephalopathy, retinopathy, nephropathy, pancreatitis or neoplasias; (ii) treat patients with diabetic disease status without symptomatic or pathologic evidence of associated sequelae but requiring better glycemic control than that offered by standard of care anti-diabetic; and (iii) patients with objective signs or symptoms of sequelae from diabetes of anti-diabetic drugs. One three-drug combination of the present invention includes a slow release PLGA-curcumin and an oral gliptin (DPP-4)-inhibitor or any incretin-mimetic and metformin.

Abstract: A method for the preparation of a bioadhesive compact matrix, which comprises the preparation of a uniform mixture of powders comprising one alkylcellulose or one hydroxy alkylcellulose and a non-water-soluble, water-swellable cross-linked polycarboxylic polymer; the preparation of compressed units starting from such powder mixture by direct compression and finally the heating of the compressed units thus obtained to a temperature in the range of 80-250° C. for a time of 1-60 minutes; the powder mixture can also comprise at least one active substance and the compressed units thus obtained are characterized by a prolonged release, and have a release kinetics of the active substance substantially of zero order in an aqueous solution at pH 4-8.

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: The present invention provides compositions and methods for using cardioprotective or hemodynamic drugs in combination with dichloroacetate enabling usage of cardioprotective or hemodynamic drugs at concentrations higher than used in normal clinical practice without increasing deleterious side effects normally associated with the cardioprotective or hemodynamic drug, thereby conferring added clinical benefit. The present invention teaches administration of DCA with cardioprotective or hemodynamic drugs as an adjunct therapy thereby conferring added clinical benefit to clinically recommended protocols.

Abstract: The invention relates to procedures and methods of determining a susceptibility to cardiac arrhythmia, including Atrial Fibrillation, Atrial Flutter and Stroke, by assessing the presence or absence of alleles at polymorphic markers found to be associated with risk of these conditions. The invention further relates to kits encompassing reagents for assessing such markers, and diagnostic 5 methods, uses and procedures for utilizing such susceptibility markers.

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.