A method and a non-rate controlled, monolithic, subsaturated patch for transdermally administering fentanyl and analogs thereof, for analgetic purposes, to a subject through skin over an extended period of time are disclosed.

Microneedle arrays for introducing an active ingredient through a skin surface of a patient can include a base layer, a plurality of microneedles projecting from the base layer, and a shell layer having an active ingredient. Each of the microneedles includes an elongate body having a proximal portion and a distal portion, in which the proximal portion is attached to the base layer. Each of the microneedles can also include at least one dissolvable polymer. The active ingredient is incorporated in the shell layer, which extends around at least a portion of the elongate body.

Pharmaceutical formulations with a tropomyosin-related kinase inhibitor (Trk inhibitor) are disclosed. The pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine in microcrystalline suspension formulations in its monohydrate form, which shows improved characteristics over the anhydrate form, and in extended release formulations. The extended release pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine-loaded microspheres.

The invention is concerned with the compounds of formula I or II:

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and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

The invention provides stable, aqueous capsaicin injectable formulations, a unit dose containing such injectable formulations, medical kits, and methods for using such injectable formulations and unit doses to treat patients suffering from pain, such as osteoarthritic knee pain. The stable, aqueous capsaicin injectable formulations may contain, for example, capsaicin, a solubilizing agent (e.g., a polyethylene glycol ester of a (C.sub.15-C.sub.25) hydroxyalkanoic acid), an antioxidant, and water.

A method is disclosed of treating pain with senicapoc, a potent Ca.sup.2+-activated K.sup.+ channel, K.sub.Ca3.1 antagonist in CNS-resident microglia. Senicapoc is shown to cause in a decrease of IL-1 and NO release from microglia cells vivo and in vitro. Because of contribution of K.sub.Ca3.1 to neuropathological processes, senicapoc is useful in the treatment of chronic, neuropathic, visceral, and inflammatory pain and the reversal of tactile allodynia.

A method is disclosed of treating pain with senicapoc, a potent Ca.sup.2+-activated K.sup.+ channel, K.sub.Ca3.1 antagonist in CNS-resident microglia. Senicapoc is shown to cause in a decrease of IL-1 and NO release from microglia cells vivo and in vitro. Because of contribution of K.sub.Ca3.1 to neuropathological processes, senicapoc is useful in the treatment of chronic, neuropathic, visceral, and inflammatory pain and the reversal of tactile allodynia.

The present disclosure relates to the composition of one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for upregulating production of DNAse1 or a sub-peptide of DNAse1. Embodiments of the present disclosure can be used as a therapy or a treatment of a conditions including acute single organ injury including drug induced liver failure, aging, atelectasis, autism, cardiovascular disease, inflammatory autoimmune conditions including sarcoidosis, rheumatoid arthritis, lupus erythematosus, and granulomatosis, patients in ICU with any pathology, and systemic inflammatory response syndrome including conditions such as sepsis and those resulting from acute tissue injury such as trauma and acute myocardial infarction.

The present disclosure relates to the composition of one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for upregulating production of DNAse1 or a sub-peptide of DNAse1. Embodiments of the present disclosure can be used as a therapy or a treatment of a conditions including acute single organ injury including drug induced liver failure, aging, atelectasis, autism, cardiovascular disease, inflammatory autoimmune conditions including sarcoidosis, rheumatoid arthritis, lupus erythematosus, and granulomatosis, patients in ICU with any pathology, and systemic inflammatory response syndrome including conditions such as sepsis and those resulting from acute tissue injury such as trauma and acute myocardial infarction.

The present invention relates to compounds, and pharmaceutically acceptable salts thereof, comprising a vascular disrupting agent (VDA) associated and a MMP proteolytic cleavage site. The compounds are useful in the treatment of cancer.