Methods and compositions for oral administration of insulin

Inventors

Kidron, Miriam • Arbit, Ehud

Assignees

Entera Bio Ltd

Abstract

This invention provides compositions comprising a protein, an absorption enhancer, a protease inhibitor, methods for treating diabetes mellitus, comprising administering same, and methods for oral administration of a protein with an enzymatic activity, comprising orally administering same.

Core Innovation

The invention provides a single, solid oral pharmaceutical composition comprising insulin, a protease inhibitor, and a compound in an effective amount to synergistically increase the bioavailability of the insulin. The protease inhibitor is selected from aprotonin and soy bean trypsin inhibitor (SBTI), and the compound is selected from N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC), N-(10-[2-hydroxybenzoyl]amino)decanoate (SNAD), a salt of SNAC or SNAD, or a combination thereof.

A specific formulation is described as protecting insulin from intestinal degradation and increasing bioavailability by combining an absorption enhancer (SNAC/SNAD and related enhancers) with a protease inhibitor. The disclosed approach is aimed at addressing degradation in the intestine while achieving improved insulin bioavailability after oral dosing.

The document further includes embodiments in which additional agents are optionally present, including omega-3 fatty acid and EDTA or salts thereof, and optionally a coating that inhibits digestion in a stomach of a subject. In human Example 1, an oral dosage form containing insulin with SNAC and a protease inhibitor (SBTI) is reported to lower blood glucose and reduce C-peptide, and is described as showing unexpected or synergistic effects versus single-agent protease inhibitor or SNAC alone.

Claims Coverage

Two independent claims define single solid oral pharmaceutical compositions in which insulin bioavailability is synergistically increased using a protease inhibitor and a SNAC/SNAD-type compound, with optional inclusion of additional agents and optional digestion-inhibiting coatings.

Across the independent claims, the core coverage is directed to single, solid oral compositions that synergistically increase insulin bioavailability by combining insulin with a protease inhibitor selected from aprotonin or SBTI and a compound selected from SNAC, SNAD, salts of SNAC/SNAD, or combinations, with optional omega-3 fatty acid and/or EDTA (or salts) and optionally a stomach-digestion-inhibiting coating.

Stated Advantages

Documented Applications