Abstract: The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives of Formula I as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 (“mGluR2”). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.

Abstract: Disclosed are a preparation method of an orexin receptor antagonist compound 5-3, Crystalline forms I-IV of an orexin receptor antagonist compound 5-3 are provided. Also provided are processes of the preparing the orexin receptor antagonist compound 5-3 and its crystalline forms, as well as methods of using the crystalline forms I-IV for treating an orexin-related disease.

Abstract: The present invention provides compounds of Formula (I), as defined in the specification, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders, cough, or itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract: Embodiments of the invention find application in the field of cancer therapy. Receptor protein kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets.

Abstract: A pharmaceutical composition including neptinib is provided. The composition includes neptinib or a pharmaceutically acceptable salt thereof, and an excipient at a low risk of compatibleness. Furthermore, the pharmaceutical composition of the present invention may also include pharmaceutically acceptable organic acid or inorganic acid as a stabilizer. The content of impurity A maintains a non-significant increase in the long-term and accelerated stability investigation for the pharmaceutical composition.

Abstract: The present application relates to novel substituted (aza)pyridopyrazolopyrimidinones and indazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired bleeding disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of menorrhagia, postpartum hemorrhage, hemorrhagic shock, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: The present invention relates to a pharmaceutical composition comprising linagliptin or a pharmaceutically acceptable salt thereof as active ingredient, wherein the pharmaceutical composition does not comprise a binder and wherein the pharmaceutical composition is obtained by direct compression.

Abstract: The specification describes the use of selected DPP IV inhibitors for the treatment of physiological functional disorders and for reducing the risk of the occurrence of such functional disorders in at-risk patient groups. In addition, the use of the above-mentioned DPP IV inhibitors in conjunction with other active substances is described, by means of which improved treatment outcomes can be achieved. These applications may be used to prepare corresponding medicaments.

Abstract: A compound represented by the following general formula (I) [the symbol in the formula are as defined in the description], a salt thereof, or the like is a RET inhibitor or RET tyrosine kinase inhibitor that can be used as an agent for the prevention or treatment of disorders including cancers and cancer metastasis having mutations in RET.

Abstract: The invention relates to a method of modeling K-Ras proteins with one or more mutations that result in constitutive activity, and identifying compounds that inhibit interactions among activated K-Ras proteins and their upstream and downstream effectors.

Abstract: The invention relates to a pharmaceutical composition comprising a combination of a compound of formula (I) or a pharmaceutically acceptable salt thereof, and at least one second agent selected from the group consisting of signal transduction pathway inhibitors, tumour immunotherapeutics, agents inhibiting the BCL2 family of proteins, agents inhibiting Mcl-1, proteasome Inhibitors, poly (ADP-ribose) polymerase (PARP) Inhibitors, aromatase inhibitors, conventional cytotoxic agents or a miscellaneous agent selected from abiraterone, ARN-509 and MYC inhibitors.

Abstract: Embodiments provided herein relate to methods and compositions for treating mesothelioma and/or a small cell lung cancer that express midkine.

Abstract: The present disclosure provides a composition consisting of ceftriaxone sodium and sulbactam sodium, a pharmaceutical formulation comprising the same and the application thereof. The composition is characterized by having an X-ray powder diffraction pattern with peaks at specific angles. The pharmaceutical formulation according to the present disclosure have better antibacterial activity and stability compared with known compositions, and are thus very suitable for the treatment of bacterial infections, especially for the treatment of refractory urogenital system infections caused by Neisseria gonorrhoeae which has drug-resistance to a variety of antibiotics (?-lactams, tetracyclines, macrolides, fluoroquinolones and aminoglycosides).

Abstract: Use of (pyrophosphato)platinum(II) or (pyrophosphato)platinum(IV) complexes (“phosphaplatin compounds”), especially (R,R)-1,2-cyclohexanediamine-(dihydrogen pyrophosphato)platinum(II) (or “PT-112”), as therapeutic agents for treatment of bone and blood cancers, or cancers that metastasize to bones, and methods thereof, are disclosed.

Abstract: Prostamide-containing biodegradable intraocular implants, prostamide compounds, prostamide-containing pharmaceutical compositions, and methods for making and using such implants and compositions for the immediate and sustained reduction of intraocular pressure and treatment of glaucoma in an eye of a patient are described.

Abstract: Disclosed herein is, among other things, a soft gel vaginal pharmaceutical composition and dosage form containing solubilized estradiol for the treatment of vulvovaginal atrophy (VVA) and female sexual dysfunction (FSD).

Abstract: Provided is a pharmaceutical composition which contains fulvestrant in an amount of 4.5% by mass to 10.0% by mass with respect to the entire mass of the pharmaceutical composition, at least one kind of polyhydric alcohol selected from propylene glycol or 1,3-butylene glycol in an amount of 8% by mass to 23% by mass with respect to the entire mass of the pharmaceutical composition, benzyl alcohol in an amount of 5% by mass to 24% by mass with respect to the entire mass of the pharmaceutical composition, benzyl benzoate in an amount of 8% by mass to 19% by mass with respect to the entire mass of the pharmaceutical composition, and castor oil, and in which a content of ethanol is less than 1% by mass with respect to the entire mass of the pharmaceutical composition, and a content of benzoic acid is less than 1% by mass with respect to the entire mass of the pharmaceutical composition.

Abstract: The present invention relates to lower dosage strength pernasal testosterone gel formulations for intranasal administration and treatment methods for using the lower dosage strength pernasal testosterone gel formulations for treating a female subject with anorgasmia and/or hypoactive sexual desire disorder.

Abstract: Compositions and methods for making a pharmaceutical dosage form include making a pharmaceutical composition that includes one or more active pharmaceutical ingredients (API) with one or more pharmaceutically acceptable excipients by thermokinetic compounding into a composite. Compositions and methods of preprocessing a composite comprising one or more APIs with one or more excipients include thermokinetic compounding, comprising thermokinetic processing the APIs with the excipients into a composite, wherein the composite can be further processed by conventional methods known in the art, such as hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.

Abstract: The invention relates to a capsule consisting of a shell and a filling, which contains plant sterol ester and/or plant stanol ester and emulsifier. The capsule is suitable for lowering serum LDL cholesterol level.

Abstract: In one aspect, the invention relates to methods for treating muscle atrophy by providing to an animal in need thereof an effective amount of a compound. The compound can modulate the expression levels of multiple mRNA of a muscle atrophy signature. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: This invention relates to the use of the combination of 25-hydroxyvitamin D3 (“25-OH D3”) and antioxidants/anti-inflammatories (ascorbic acid, vitamin E and at least one carotenoid) to make a pharmaceutical, nutraceutical or food supplement which can ameliorate various problems observed in humans connected with polycystic ovarian 5 syndrome and cardiovascular diseases. Pharmaceuticals, nutraceuticals and food supplements containing the 25-OH D3 and antioxidants/anti-inflammatories and premixes are also provided.

Abstract: The method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient's normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient's normal historical physiological range between doses of Vitamin D hormone replacement therapies.

Abstract: Disclosed are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof, and in particular, provided are a compound of formula (I), and an isomer, a pharmaceutically acceptable salt, a hydrate and a solvate thereof, and the corresponding pharmaceutical composition. The present invention also provides uses of the present compounds, alone or in combination with other antiviral drugs, in the treatment of the diseases caused by hepatitis B virus (HBV), hepatitis D virus (HDV) and human immunodeficiency virus (HIV).

Abstract: To provide a multidrug-resistant Gram positive bacteria antibacterial agent containing as an active ingredient a novel component to which multidrug-resistant bacteria are not resistant, and an external agent containing the same. The multidrug resistant Gram-positive bacteria antibacterial agent according to the present invention contains an amphipathic compound having an HLB value of greater than 9.5 and 20 or less and an acyl group as an active ingredient. The external agent according to the present invention contains the multidrug resistant Gram-positive bacteria antibacterial agent.

Abstract: The present invention relates to methods of treating infectious, inflammatory and post-traumatic disorders by administering various compounds newly discovered to have TLR4 inhibitory activity. In addition to methods of treatment, the present invention further provides for pharmaceutical compositions comprising said compounds, together with a suitable pharmaceutical carrier.

Abstract: The present invention relates to a method for treating a cancer with the combination of a topoisomerase II inhibitor (TOP2 inhibitor) and a histone deacetylation inhibitor (HDACi), provides synergistic cancer cell-killing effects, and prolonged overall survival, especially when the expression of checkpoint kinase 1 (CHK-1) is low.

Abstract: Provided herein are alpha2-selective Na,K-ATPase inhibitors and prodrugs thereof, characterized by having a cyclic moiety attached to a digoxin or digitoxin derivative, as well as uses thereof in lowering intraocular pressure and in treating glaucoma and heart conditions.

Abstract: Pharmaceutical compositions comprising a first anti-acne compound, a second anti-acne compound, and an anti-photoaging compound are described. Methods for the treatment of acne and photoaging using the compositions are also described.

Abstract: The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

Abstract: A composition for the enhancement of free testosterone is provided, the composition comprising: vitamin B6; vitamin B12; zinc; L-citrulline; fenugreek seed extract; an adenosine triphosphate (ATP) stimulating component, comprising: ancient peat extract, and apple fruit extract; eurycoma root extract; and boron. A method of increasing free testosterone is provided, the method comprising administering to an individual an effective dose of a composition comprising: vitamin B6; vitamin B12; zinc; L-citrulline; fenugreek seed extract; an adenosine triphosphate (ATP) stimulating component, comprising: ancient peat extract, and apple fruit extract; eurycoma extract; and boron.

Abstract: Oral sorbent compositions that bind small and charged toxins and methods of use.

Abstract: The present invention provides methods and compositions for treating and preventing conditions characterized by infection and/or inflammation, especially of the eyes, ears, nose, and/or throat. The methods of the invention involve administering hypohalous acid to the patient, such as in the form of a composition described herein.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: Compositions and methods of promoting wound healing in a human by administering to the human mesenchymal stem cells in an effective amount.

Abstract: This application discloses alginate microencapsulation-mediated differentiation of embryonic stem cells and use of the stem cell differentiation method for the development of effective treatment of various diseases and disorders. The microencapsulation of embryonic stem (ES) cells results in decreased cell aggregation and enhanced neural lineage differentiation through incorporating the soluble inducer retinoic acid (RA) into the permeable microcapsule system. This differentiation process can be augmented by differentiation pathway regulators such as PPAR agonists.

Abstract: Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Abstract: Methods and therapeutics are provided for treating metabolic disorders by increasing activation of brown adipose tissue. Generally, the methods and therapeutics can increase activation of brown adipose tissue to increase energy expenditure and induce weight loss. In one embodiment, a method for increasing activation of brown adipose tissue includes modifying brown adipocytes to express a gene that activates brown adipocytes, such as uncoupling protein 1. In another embodiment, a method for increasing brown adipose tissue activation includes increasing the number of brown adipocytes. This can be accomplished by inducing proliferation of adipocytes in vivo or expanding adipocytes ex vivo, transplanting adipocytes into brown adipose tissue depots or elsewhere and inducing differentiation of adipocyte progenitor cells, such as MSCs, adipocyte progenitor cells, pre-adipocytes and adipocyte precursor cells.

Abstract: The present invention provides novel stem cell compositions having significant therapeutic and practical advantages, as well as methods of preparing and using such compositions for the treatment and prevention of injury and disease in patients. The invention may be applied to stem cell populations isolated from a wide variety of animals, including humans, and tissues. In particular applications, the invention is used to prepare a stem cell composition from a collagen-based tissue, such as adipose tissue, isolated from a patient, and the stem cell composition is subsequently provided to a site of actual or potential injury in the patient. The invention further includes related kits comprising the stem cell compositions, which are remarkably stable and retain viability and efficacy during storage and shipment.

Abstract: The invention relates to an encapsulating chamber for secreting cells, comprising a closed shell made of a semi-permeable membrane, said membrane comprising at least one layer of porous biocompatible polymer, and one layer of non-woven biocompatible polymer.

Abstract: Disclosed herein is a method for manufacturing a population of human insulin producing cells from non-pancreatic ?-cells, wherein the resulting insulin producing cells have increased insulin content, or increased glucose regulated secretion of insulin, or a combination of both.

Abstract: Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Abstract: A method of conditioning a subject in need of transplantation of progenitor cells in suspension of a tissue of interest is disclosed. The method comprising: (a) administering to a subject a therapeutically effective amount of an agent capable of inducing damage to the tissue of interest, wherein the damage results in proliferation of resident stem cells in the tissue; and subsequently (b) subjecting the subject to an agent which ablates the resident stem cells in the tissue. A method of transplanting progenitor cells in suspension of a tissue of interest to a subject in need thereof is also disclosed.

Abstract: Administering a pulmonary surfactant and a corticosteroid is effective for the treatment of evolving bronchopulmonary dysplasia (BPD) in preterm neonates.

Abstract: The present invention relates to treatment of pulmonary fibrosis with umbilical mesenchymal stem cell.

Abstract: The present invention provides formulation/composition comprising phytonutrients with natural chlorotoxins for targeting cancer, infection, inflammation and pain without any side effects and a method for synthesizing the same. The raw materials are cleaned and dried and to prepare coarse powder of 40 mesh size, extracted with solvent (comprising water:alcohol in a ratio of 40:60) in a ratio of 4:1 with overnight soaking. Prior to cold extraction, the mixture is macerated for 4 hours. The mixture is refluxed for 2 hours at 80° C. The addition of ethanol, maceration and refluxing steps are repeated three times and above solvent is added, if required. The residue is checked for complete extraction after every refluxing step. The extract/residue is filtered and concentrated under vacuum. The extract/residue is vacuum tray dried at 70-80° C. for 12 hours. The extract/residue is scraped and dried lumps of the extract/residue are milled. The extract/residue is sieved and packed.

Abstract: The present invention provides formulation/composition comprising phytonutrients with natural chlorotoxins for targeting cancer, infection, inflammation and pain without any side effects and a method for synthesizing the same. The raw materials are cleaned and dried and to prepare coarse powder of 40 mesh size, extracted with solvent (comprising water:alcohol in a ratio of 40:60) in a ratio of 4:1 with overnight soaking. Prior to cold extraction, the mixture is macerated for 4 hours. The mixture is refluxed for 2 hours at 80° C. The addition of ethanol, maceration and refluxing steps are repeated three times and above solvent is added, if required. The residue is checked for complete extraction after every refluxing step. The extract/residue is filtered and concentrated under vacuum. The extract/residue is vacuum tray dried at 70-80° C. for 12 hours. The extract/residue is scraped and dried lumps of the extract/residue are milled. The extract/residue is sieved and packed.

Abstract: Pharmaceutical compositions are disclosed that includes a therapeutically effective amount of a purified viable Gram negative bacteria and a pharmaceutically acceptable carrier. The pharmaceutical compositions are formulated for topical administration. Methods of treating atopic dermatitis using these pharmaceutical compositions are also disclosed.

Abstract: Disclosed is a stable probiotic composition containing Bacillus coagulans MTCC 5856 exhibiting increased viability over wide range of pH and the use of flow cytometry method to enumerate the viable count of Bacillus coagulans MTCC 5856 under various environmental conditions.