The present disclosure relates to methods for treating type 1 diabetes (T1D) using a glucagon receptor blocking agent. More specifically, the present disclosure relates to methods for treating T1D using substantially lower doses of insulin supple-mentation, or even in the absence of insulin supplementation, using antigen binding and antagonizing proteins, e.g., fully human antibodies that specifically bind to and antagonize the function of the human glucagon receptor.

In order to provide a prophylactic and/or therapeutic agent for Trk-related diseases, the present invention provides a compound which has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and in addition thereto, is excellent in solubility and absorbability against free bases. The compound of the present invention has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and is excellent in solubility and absorbability against free bases, and is therefore useful as a prophylactic and/or therapeutic agent for Trk-related diseases.

The invention provides novel, multiply-substituted 1-aryl-3-azabicyclo[3.1.0]hexanes, and related processes and intermediates for preparing these compounds, as well as compositions and methods employing these compounds for the treatment and/or prevention of central nervous system (CNS) disorders, including depression and anxiety.

Certain tetrahydro-pyrimidoazepine compounds are described, which are useful as TRPV1 modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by TRPV1. Thus, the compounds may be administered to treat, e.g., pain, itch, cough, asthma, or inflammatory bowel disease.

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

The present invention provides methods for cellular seeding onto three-dimensional fibroblast constructs, three-dimensional fibroblast constructs seeded with muscle cells, and uses therefore.

The present invention relates to the use of an additive in a transdermal therapeutic system with an active agent-containing layer in the form of a biphasic layer having a hydrophilic inner phase and a hydrophobic outer phase, in which the inner phase includes the additive and an active agent dissolved therein. The additive has a higher affinity to water than to the active agent and controls the permeation rate of the active agent in a manner which is independent from its concentration in the biphasic layer, with the maintenance of the permeation rate being proportional to the amount of active agent in the biphasic layer.

Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-{4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4′-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid.

Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-{4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4′-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.