Methods and compositions for oral administration
Inventors
Assignees
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Publication Number
US-10420721-B2
Publication Date
2019-09-24
Expiration Date
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 relates to an oral pharmaceutical composition for oral administration that is a solid composition comprising a protein having a molecular weight of up to 100,000 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 protease inhibitor is a serpin, and the serpin is a trypsin inhibitor.
The problem addressed is improving oral protein delivery by protecting a protein from intestinal cleavage and increasing absorption/bioavailability through the intestinal mucosa. The system uses a compound selected from NAC and NAD (or salts) as an absorption enhancer together with a protease inhibitor that is a serpin trypsin inhibitor to support delivery of proteins following oral administration.
Embodiments described include using specific proteins and absorption-enhancer/protease-inhibitor combinations for diabetes treatment, including insulin, Exenatide, and GLP-1 or GLP-2-related proteins. Additional embodiments include optional additives and delivery forms such as enteric/gelatin coatings intended to inhibit digestion in the stomach, and microencapsulation-related embodiments, as well as optional components including EDTA/Na-EDTA and omega-3 fatty acid.
Human subject data are provided showing a synergistic effect on blood glucose and C-peptide when the absorption enhancer is used together with the protease inhibitor, where the combined approach is reported to reduce blood glucose and C-peptide beyond use of a single protease inhibitor alone.
Claims Coverage
The independent claims explicitly cover an oral solid pharmaceutical composition with a protein of molecular weight up to 100,000 Daltons, a serpin that is a trypsin inhibitor, and a selected absorption-enhancer compound from NAC/NAD, including salt forms. Dependent claims refine inhibitor selection, enhancer salt forms, optional additives, digestion-inhibiting coatings, an oral administration to a subject aspect, and synergy to increase protein bioavailability.
Oral solid composition with protein up to 100,000 Daltons plus serpin trypsin inhibitor and NAC/NAD enhancer
A pharmaceutical composition for oral administration that is a solid composition comprising a protein having a molecular weight of up to 100,000 Daltons; a protease inhibitor that is a serpin and a trypsin inhibitor; and a compound selected from NAC, NAD, a salt of said NAC or said NAD, and combinations thereof.
Oral administration to a subject with protein molecular-weight ceiling
A method aspect of orally administering to a subject a pharmaceutical composition containing a protein having a molecular weight of up to 100,000 Daltons.
Across the independent-claim coverage, the core inventive concept is an oral solid pharmaceutical composition that combines a protein, a serpin trypsin inhibitor protease inhibitor, and an absorption-enhancer compound selected from NAC/NAD, including salts, with refinements in dependent claims selecting specific serpin/trypsin inhibitors, defining NAC/NAD salt forms, optionally adding omega-3 fatty acid and EDTA/salt, and optionally using digestion-inhibiting enteric/gelatin coatings.
Stated Advantages
Increases protein bioavailability.
Synergistically reduces blood glucose and C-peptide when the absorption enhancer is used together with the protease inhibitor.
Documented Applications
Oral administration of the composition for diabetes treatment, with human subject data including blood glucose and C-peptide outcomes.
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