Abstract: A method of reducing the liver toxicity of a liver-damaging agent is disclosed. The method comprises administering to the subject: (i) the liver-damaging agent; and (ii) an agent which alters the circadian rhythmicity of microbes of the gut microbiome of the subject.

Abstract: The present invention relates to a pharmaceutical composition containing, as an active ingredient, niclosamide or pharmaceutically acceptable salts thereof, for treating or preventing disease related to Axin-GSK3 interaction, such as familial adenomatosis polyposis (FAP). According to the present invention, familial adenomatosis polyposis (FAP) which causes pain due to lack of specific treatment methods, can be effectively treated using niclosamide, which is a safe drug approved by the FDA.

Abstract: The present disclosure provides stabilized sulforaphene compositions and uses thereof. The compositions include a stabilized sulforaphene, such as sulforaphene-cyclodextrin complex, that increases the efficacy, biological activity and stability of isolated sulforaphene. The present disclosure also includes pharmaceutical and nutraceutical compositions and methods for the treatment of mitochondrial disorders and muscular disorders. In addition, methods for increasing ATP and/or FAD production in cells by the administration of a stabilized sulforaphene are provided.

Abstract: An aqueous ibuprofen and paracetamol composition has a pH 6.3-7.3. The composition can be used as a medicament, especially for the treatment of pain and/or inflammation. The composition can be formulated for intravenous injection.

Abstract: The present invention relates to crystalline polymorphic forms of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate (“SNAC”), including two hydrates, a methanol solvate, and an ethanol solvate, of SNAC. More specifically, the present invention provide six polymorphic forms of SNAC (hereafter referred to as Forms I-VI). The present invention also provides an amorphous form of SNAC.

Abstract: The present invention relates to controlled release pharmaceutical compositions comprising fumaric acid ester(s) as active substance(s). The compositions are suitable for use in the treatment of e.g. psoriasis or other hyperproliferative, inflammatory or autoimmune disorders and are designated to release the fumaric acid ester in a controlled manner so that local high concentrations of the active substance within the gastrointestinal tract upon oral administration can be avoided and, thereby, enabling a reduction in gastro-intestinal related side-effects.

Abstract: In various embodiments, the present invention provides methods of reducing the risk of a cardiovascular event in a subject on statin therapy and, in particular, a method of reducing the risk of a cardiovascular event in a subject on statin therapy having a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of eicosapentaenoic acid ethyl ester or a derivative thereof.

Abstract: The present invention provides compositions comprising a poorly water soluble pharmaceutical agent, a carrier protein, and an antimicrobial agent, wherein significant microbial growth is inhibited in the composition. The amount of the antimicrobial agent in the composition may be below the level that induces a toxicological effect or at a level where a potential side effect can be controlled or tolerated. Also provided are compositions comprising a poorly water soluble pharmaceutical agent, a carrier protein, a sugar, and optionally an antimicrobial agent. Methods of using the compositions are also provided.

Abstract: The disclosed subject matter provides methods of using nitroxyl donating compounds and pharmaceutical compositions comprising such compounds in a dose escalation regimen.

Abstract: A topical composition and method comprising administering physiological effective amounts of at least two active components forskolin combined with one or more lubricating base components. Active components may include one or more of L-arginme free base, hydrochloride salt, ethyl ester or combinations thereof.

Abstract: A therapeutic compound has a modified phenolic compound of the general formula (I) wherein at least one of R, R1, R2, R3, and R4 is an electrophilic group chosen from halogen, aldehyde, haloalkane, alkene, butyryl, flurophenol, sulfonamide, flurophenol sulfoxide and the remaining R, R1, R2, R3, and R4 is are each independently hydrogen, a hydroxyl group, an alkoxy group, a rutinosyl group, a carboxyl group, chromone, benzopyran, a rhamnosyl group, a substituted alkoxy group or a substituted acyloxy group wherein the substituent is chosen from hydroxyl, alkoxy, aryloxy, phenyl, halogen, and amido group. The compound can be used in a therapeutic treatment of inflammatory related diseases and condition.

Abstract: The present invention provides a pharmaceutical composition comprising: a) a therapeutically effective amount of at least one cannabinoid receptor binding ligand, and b) a liquid vehicle comprising at least one semifluorinated alkane; as well as the use of such pharmaceutical compositions as a medicament.

Abstract: Provided herein is a method of treating, preventing, or alleviating one or more symptoms of Chagas disease in a subject, comprising administering to the subject (i) ascorbic acid, or a single enantiomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and (ii) a quinone compound, or a single enantiomer, a mixture of enantiomers, or a mixture of diastereomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

Abstract: An object of the present invention is to provide a pharmaceutical composition comprising 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof at a high concentration, with a characteristic bitter taste masked, and a manufacturing method thereof. The present invention provides a pharmaceutical composition comprising fine granules having a core comprising 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof, and a binder; and a polymer layer with which a surface of the core is coated, wherein the fine granules have a roundness of 0.8 or more and a content of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or the salt thereof in the fine granules is 30 to 90% by mass.

Abstract: An object of the present invention is to provide a composition for external use having an improved skin permeability of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof. The present invention provides a composition for external use comprising 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof, one or more solvents selected from the group consisting of alcohols, sulfoxides and amides, and a permeation enhancer.

Abstract: Substituted phenylpyrrolecarboxamide compounds such as those represented by Formula A can be used in the treatment of HIV infection and related conditions.

Abstract: Described herein are methods for treating one or more skin conditions by administering, via the sublingual or buccal route, a composition comprising substituted or unsubstituted diindolylmethane. In particular, methods are provided for improving the bioavailability and pharmacokinetic parameters of substituted or unsubstituted diindolylmethane following a sublingual or buccal administration, relative to an oral administration.

Abstract: Polymorph forms of 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2(1H)-yl)-benzamide are disclosed as well as their methods of synthesis and pharmaceutical compositions.

Abstract: A method for suppressing a plasma concentration of an asenapine metabolite includes applying to a subject a patch comprising a support layer and an adhesive agent layer, the adhesive agent layer includes asenapine and/or a pharmaceutically acceptable salt thereof, and an adhesive base agent.

Abstract: The present invention provides means to affect the dynamics of actomyosin network in natural killer (NK) cells, and thereby to confer selective control on killing efficiencies of NK cell populations. Compositions and methods of the present invention, particularly those using small molecules, provide a powerful tool for controlling NK cell activation and function in various conditions, in health and disease, most notably in viral infections, autoimmunity, immunodeficiency, GVHD and cancer.

Abstract: The present invention is directed to cell-protective, in particular, cardio- and renal-protective organic compounds, preferably to organic compounds that inhibit substrate phosphorylation by the G-protein-coupled receptor kinase 2 (GRK2, ADRBK1). Preferably, the organic compounds inhibit the GRK2-mediated phosphorylation of serine/arginine-rich splicing factor 1 (SRSF1, ASF-1, SF2) and/or phosducin for treating hypertension, heart diseases, heart dysfunction or failure and heart disease-associated pathologies, e.g. cardiomyocyte necrosis, ischemic cardiac disease and/or ischemic heart damage or ageing. Furthermore, the present invention is directed to a method for the identification of inhibitors of the (GRK2)-mediated phosphorylation of (SRSF1) and/or phosducin.

Abstract: In one embodiment, the present invention provides a combination of a Type I protein arginine methyltransferase (Type I PRMT) inhibitor and an immuno-modulatory agent selected from: an anti-PD-1 antibody or antigen binding fragment thereof, an anti-PDL1 antibody or antigen binding fragment thereof, and an anti-OX40 antibody or antigen binding fragment thereof. In another embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a Type I protein arginine methyltransferase (Type I PRMT) inhibitor and a second pharmaceutical composition comprising a therapeutically effective amount of an immuno-modulatory agent selected from: an anti-PD-1 antibody or antigen binding fragment thereof, an anti-PDL1 antibody or antigen binding fragment thereof, and an anti-OX40 antibody or antigen binding fragment thereof.

Abstract: The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

Abstract: Disclosed herein are topical formulations comprising about 0.001 to about 3 wt % detomidine or a salt thereof; and, a carrier that is suitable for topical administration to a subject's skin, wherein the carrier optionally comprises a water-miscible solubilizer that is present in an amount of up to 40% by weight of the formulation; wherein the formulation has a pH of 4.5 to 9, and, wherein the formulation provides prolonged, substantially non-systemic treatment for pain. Also provided are methods for providing prolonged, non-systemic treatment for pain in a subject in need thereof comprising topically administering to the subject the presently disclosed topical formulations.

Abstract: The disclosure includes the use of cenicriviroc or a salt or solvate thereof and pharmaceutical compositions containing the same in the treatment of inflammation and connective tissue diseases and disorders, such as fibrosis, peritonitis, and liver injury.

Abstract: The present invention is directed to a combination comprising a proteasome inhibitor and a compound of formula I or a pharmaceutically acceptable salt thereof: to a pharmaceutical composition and to a kit both comprising said combination, to the combination, composition or kit for use in the treatment of cancer, and to a method of treatment of cancer in a patient in need thereof comprising administering to said patient an effective amount of said combination, composition or kit.

Abstract: For the prevention of parasite infestation of animals, an isoxazoline can be administered by drinking water route. However the inventors have found that when the drinking water is sanitized, for instance by using hypochlorite, the isoxazoline becomes degraded. Surprisingly, the isoxazoline can be protected from degradation by the use of a vitamin E. A pharmaceutical composition can now be prepared containing a concentrated solution of the isoxazoline in a solvent and co-solvent, with vitamin E. The composition can be diluted in drinking water, even when sanitized, to prepare medicated drinking water for animals. This way an anti-parasitic treatment can be mass-administered, leading to a highly effective reduction of the parasite infestation of an animal, and its surroundings.

Abstract: The present invention is directed to methods of treating, preventing, and/or ameliorating systemic sclerosis, by administration of a therapeutically effective amount of ifetroban or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to methods of treating hepatorenal syndrome by administration of a therapeutically effective amount of a thromboxane A2 receptor antagonist to a patient in need thereof. The present invention is also directed to methods of treating hepatic encephalopathy and cerebral edema by administration of a therapeutically effective amount of a thromboxane A2 receptor antagonist to a patient in need thereof.

Abstract: In an aspect, the invention relates to compositions and methods for treating sepsis, including but not limited neonatal sepsis and sepsis related to infection. In an aspect, the invention relates to compositions and methods for attenuating adverse conditions of sepsis resulting from enterovirus infection. In an aspect, the invention relates to improved formulations of antiviral agents such as pleconaril for the treatment, alleviation and prevention of conditions associated with sepsis.

Abstract: The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt(s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).

Abstract: The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various CNS diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3?,5?-monophosphate (cGMP) or both, or an upregulation of the NO pathway is desirable.

Abstract: Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

Abstract: The present invention provides crystalline forms of Deutetrabenazine. Specific crystalline forms provided by the present invention include Deutetrabenazine Form APO-I, a co-crystal of Deutetrabenazine and quercetin, and Deutetrabenazine Form APO-II, a co-crystal of Deutetrabenazine and luteolin. Also provided are pharmaceutical compositions including the Deutetrabenazine crystalline forms, and the use of these forms in the treatment of tardive dyskinesia and chorea associated with Huntington's disease.

Abstract: The present invention provides a pharmaceutical composition containing an inhibitor selected from the group consisting of an EZH1 inhibitor, an EZH2 inhibitor and an EZH1/2 dual inhibitor as an active ingredient, for use in treating HTLV-1-associated myelopathy. The present invention provides a pharmaceutical composition for use in treating HTLV-1-associated myelopathy, containing a 1,3-benzodioxole derivative or a pharmaceutically acceptable salt thereof.

Abstract: Provided is a method of treating or lessening the severity of pain in a subject, comprising administering to the subject a compound of formula (I), defined as described herein, or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are pharmaceutical compositions that are useful for the treatment of hypertension comprising an angiotensin II receptor blocker, a diuretic, and a calcium channel blocker.

Abstract: This application describes compounds that can act as opioid receptor ligands, which compounds can be used in the treatment of, for example, pain and pain related disorders.

Abstract: This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.

Abstract: The present disclosure relates to methods of treating prostate cancer by administering an effective amount of sirolimus locally to the prostate of a subject in need thereof. In particular, the present disclosure provides methods of treating prostate cancer by intratumoral injection of a liquid formulation comprising sirolimus in which the amount of sirolimus administered is well above the dosage used for preventing transplant rejection.

Abstract: Disclosed herein are methods for treating glaucoma and reducing intraocular pressure. Methods for treating glaucoma include administering a cannabinoid receptor antagonist to a subject in need thereof. Methods for reducing intraocular pressure include administering a cannabinoid receptor antagonist to a subject in need thereof. Methods for treating glaucoma also include administering a negative allosteric modulator of a cannabinoid CB1 receptor to a subject in need thereof. Methods for reducing intraocular pressure also include administering a negative allosteric modulator of a cannabinoid CB1 receptor to a subject in need thereof.

Abstract: In certain embodiments, the present disclosure is directed to methods and uses for treating seizure disorders in a human, wherein the methods and uses comprise orally administering a therapeutically effective amount of the voltage-gated potassium channel allosteric modulator, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (Compound A), to the human in need thereof, for example, under fed conditions. The present disclosure is further directed to various improved methods of therapy and administration of Compound A.

Abstract: Disclosed herein are methods for treating solid tumors by direct injection into the tumors of chemotherapeutic particles, methods for inhibiting tumor metastasis by administering chemotherapeutic particles to a subject having a tumor, and compositions that include chemotherapeutic particles, small amounts of a polysorbate, and a carrier.

Abstract: The present invention relates to the use of substituted quinoline compounds for treating immunoglobulin light chain (LC) amyloidosis (AL), especially cardiotoxicity associated with immunoglobulin LC AL. In particular, the substituted quinoline compounds useful in the treatment of cardiac LC amyloidosis are 5,7-dihalo-8-hydroxyquinoline derivatives, especially 5,7-dichloro-8-hydroxyquinoline derivatives.

Abstract: Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Abstract: The present invention relates to efflux inhibitor compounds, compositions, and methods of using the same. More specifically, the instant invention comprises deuterated analogs of tariquidar with superior pharmacokinetic properties such that it is now possible to facilitate accumulation and distribution of therapeutic agents to effective levels in cells or compartments protected by efflux transporter proteins such as P-Glycoprotein (P-GP) and Breast Cancer Resistance Protein (BCRP). Such pump protected compartments include brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, stem cells, and solid tumors. In other embodiments, the present invention comprises methods of using the instant deuterated analogs.

Abstract: Provided herein are Camptothecin Conjugates, Camptothecin-Linker Compounds, Camptothecin Compounds, intermediates thereof, and method of preparing the same. Also provided herein are methods of treating cancer and autoimmune diseases with the Conjugates described herein.

Abstract: The present invention relates to improved compositions and methods for the treatment or prevention of various diseases, including forms of depression, including, for example, breakthrough depression and treatment-refractory depression, and other mood disorders, as well as Parkinson's disease, bipolar disorder, bipolar disorder, attention deficit disorder (ADHD), Restless Leg Syndrome (RLS), and obesity. In some embodiments, the compositions and methods comprise low dose naltrexone or related opioid antagonists.

Abstract: The disclosure generally relates to tamper-resistant transdermal dosage forms. The dosage forms can comprise an active agent and more than one antagonist reservoir.

Abstract: The invention relates to new crystalline modifications of the hydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine, crystalline modification of the dihydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine and amorphous 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride which are suitable in particular for the preparation of solid medicaments for the treatment or prevention of depressive disorders, anxiety disorders, bipolar disorders, mania, dementia, substance-related disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleeping disorders, psychiatric disorders, cerebral infarct, tension, for the therapy of side-effects in the treatment of hypertension, cerebral disorders, chronic pain, acromegaly, hypogonadism, secondary amenorrhea, premenstrual syndrome and undesired puerperal lactation.