A topical cyclooxygenase (COX) inhibitor formulation comprising an inhibitor of COX-1 and/or COX-2, one or more long chain monounsaturated fatty acids, long chain monounsaturated fatty alcohols, terpenes, or combinations thereof; and a solvent mixture comprising ethanol, propylene glycol, 2-(2-Ethoxyethoxy)ethanol, and optionally dimethylsulfoxide.

This disclosure relates to the field of therapeutic protein kinase inhibitors, in particular receptor-interacting protein kinase 1 (“RIPK1”) inhibitor for treatment of subjects with conditions involving systemic hyperinflammatory responses, such as Cytokine Release Syndrome (CRS), or Systemic Inflammatory Response Syndrome (SIRS), sepsis, organ damage, or hyperinflammatory state associated with infectious diseases.

This disclosure relates to the field of therapeutic protein kinase inhibitors, in particular receptor-interacting protein kinase 1 (“RIPK1”) inhibitor for treatment of subjects with conditions involving systemic hyperinflammatory responses, such as Cytokine Release Syndrome (CRS), or Systemic Inflammatory Response Syndrome (SIRS), sepsis, organ damage, or hyperinflammatory state associated with infectious diseases.

Ready to use liquid formulations of diclofenac potassium are disclosed which are particularly well suited for packaging in stick-packs.

Ready to use liquid formulations of diclofenac potassium are disclosed which are particularly well suited for packaging in stick-packs.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

Compositions comprising an aqueous medium, lipids and nonionic surfactants and methods of their use in preventing skin damages, such as in subjects exposed to radiation, are provided.

Compositions comprising an aqueous medium, lipids and nonionic surfactants and methods of their use in preventing skin damages, such as in subjects exposed to radiation, are provided.

In a delayed release formulation comprising a core containing a drug and a delayed release coating for providing intestinal release, release of the drug in the colon is accelerated by including an isolation layer between the core and the delayed release coating. The delayed release coating comprises an inner layer and an outer layer. The outer layer comprises a pH dependently soluble polymeric material which has a pH threshold at about pH 5 or above. The inner layer comprises a soluble polymeric material which is soluble in intestinal fluid or gastrointestinal fluid, said soluble polymeric material being selected from the group consisting of a polycarboxylic acid polymer that is at least partially neutralised, and a non-ionic polymer, provided that, where said soluble polymeric material is a non-ionic polymer, said inner layer comprises at least one additive selected from a buffer agent and a base.