Methods and compositions for oral administration

Inventors

Kidron, Miriam • Arbit, Ehud

Assignees

Entera Bio Ltd

Abstract

This invention provides compositions comprising a protein, an absorption enhancer, a protease inhibitor, method 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 is directed to a pharmaceutical composition for oral administration that includes a protein having a molecular weight of up to 150,000 Daltons, a protease inhibitor, and a compound selected from N-(8-[2-hydroxybenzoyl]amino) caprylate (NAC), N-(10-[2-hydroxybenzoyl]amino)decanoate (NAD), a salt of said NAC or said NAD, and combinations thereof. The compound is present in an amount in a range of from 70% to 99.4% by weight. In the described composition, the protease inhibitor is a serpin, and the serpin is a trypsin inhibitor.

In at least one described composition context, the protein is PTH, and the specific formulation includes a defined trypsin-inhibiting serpin protease inhibitor together with the selected NAC/NAD compound. The disclosed framework reflects combining an absorption enhancer function from NAC or NAD with protease inhibition from a trypsin-inhibiting serpin to support oral delivery of an enzymatically active protein.

The document reports oral delivery of enzymatically active proteins and describes human subject data for insulin formulations that combine SNAC with the trypsin inhibitor SBTI and/or with aprotinin, including unexpected or synergistic effects such as significant reductions in blood glucose and C-peptide levels compared with controls. The same overall concept is extended to additional formulation components, including omega-3 fatty acids and/or EDTA or Na-EDTA, and to digestion-inhibiting coatings such as enteric, gelatin, and microencapsulation approaches.

Claims Coverage

One independent claim is identified (clm-00001). It specifies three principal inventive ingredients and constraints: (i) an oral protein with a defined molecular-weight limit, (ii) a serpin trypsin inhibitor protease inhibitor, and (iii) a specific hydroxybenzoyl caprylate/decanoate absorption-related compound (NAC/NAD or salts) present at a specified high weight fraction.

Across the identified independent claim, the coverage is centered on an oral pharmaceutical composition combining a molecular-weight constrained protein up to 150,000 Daltons, a serpin trypsin inhibitor protease inhibitor, and NAC/NAD or salts at 70% to 99.4% by weight, with PTH as an example protein.

Stated Advantages

Documented Applications