Methods and compositions for treating conditions associated with an abnormal inflammatory response

Inventors

Glick, Gary D. • Franchi, Luigi • Santus, Giancarlo

Assignees

Entero Therapeutics Inc

Abstract

This disclosure features chemical entities (e.g., a compound exhibiting activity as a mitochondrial uncoupling agent or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as niclosamide or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as a niclosamide analog, or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof) that are useful, e.g., for treating one or more symptoms of a pathology characterized by an abnormal inflammatory response (e.g., inflammatory bowel diseases) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

Core Innovation

The invention describes a method for treating colitis by administering, by enema, an effective amount of a formulation prepared by mixing a first component comprising a solid pharmaceutical composition and a second component comprising one or more liquids and optionally one or more other pharmaceutically acceptable excipients forming a liquid carrier. The solid pharmaceutical composition comprises an inner phase and an external phase, and the inner phase is a wet granulated solid preparation comprising niclosamide, or a pharmaceutically acceptable salt thereof, together with one or more disintegrants, one or more diluents, and one or more binders.

The external phase comprises one or more glidants and/or one or more lubricants, providing a defined two-phase solid composition structure for combination with the liquid carrier. The document further characterizes niclosamide and niclosamide analogs as chemical entities including salts, hydrates, and cocrystals, and associates their use with treating symptoms of inflammatory pathologies with abnormal inflammatory responses.

The mechanism is proposed as mitochondrial uncoupling in pathogenic T cells leading to T-cell death, and the document emphasizes local administration to reduce systemic toxicity. Colitis treatment is described for inflammatory bowel disease such as ulcerative colitis and Crohn’s disease.

Claims Coverage

The independent claim coverage centers on a colitis treatment method with enema administration of a two-component formulation built from a wet-granulated niclosamide solid inner phase, an external phase, and a liquid carrier. Across the input items, three inventive features are consistently present.

Overall, the claim coverage is anchored on enema delivery of a formulation that combines a wet-granulated inner phase containing niclosamide or a pharmaceutically acceptable salt with defined disintegrants, diluents, and binders, an external phase containing glidants and/or lubricants, and a liquid carrier made from one or more liquids and optional pharmaceutically acceptable excipients.

Stated Advantages

Documented Applications