AC-Aa-NS Oral Peptide Composition for Stable Bioavailability
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Solution Overview
Problem
Current peptide and protein therapies face challenges in oral delivery due to low bioavailability, variability, slow solubilization, and aggressive absorption, particularly for non-cyclic or non-pegylated peptides and small cyclic peptides, with existing cyclic non-pegylated peptides, with existing cyclic non-pegylated proteins, with existing cyclic non-pegylated peptides, with existing cyclic non-acylated or non-pegylated materials, with Rybelsus® as marketed peptide product, which has drawbacks like low bioavailability, great variability, and slow solubilization.
Innovation Solution
A composition comprising an acylated amino acid (AC-aa-NS) as a permeation enhancer, formulated with a peptide or protein, improves bioavailability and reduces variability by providing a solid oral dosage form that includes AC-aa-NS, a protease inhibitor, and optionally a lubricant or pH modifier, with specific alkyl and amino acid side chain configurations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If peptides or proteins are administered orally, then patient comfort and treatment compliance improve, but bioavailability remains low and highly variable
Solution Approach 1:
The invention uses a composite formulation containing acylated amino acids (such as sodium caprate, sodium caprylate, or sodium salicylate) combined with the peptide or protein therapeutic. This composite approach allows the peptide to be delivered orally while the acylated amino acid enhances intestinal absorption, achieving both patient convenience and reliable bioavailability
Solution Approach 2:
The invention modifies the chemical parameters of the formulation by using acylated amino acids with specific chain lengths (C6-C12) and structures. These parameter changes in the formulation enable the peptide to withstand gastric conditions and achieve consistent absorption in the intestine, resolving the bioavailability variability issue
2Reliability
If a permeation enhancer is used to improve oral absorption, then bioavailability increases, but solubilization speed decreases
Solution Approach 1:
The invention selects acylated amino acids with optimal chain lengths (C6-C12) and structures that balance permeation enhancement with solubilization properties. This parameter optimization allows the formulation to achieve both improved bioavailability and adequate dissolution rate in the gastrointestinal tract
Solution Approach 2:
The acylated amino acid provides localized enhancement at the intestinal absorption site without requiring rapid system-wide solubilization. The formulation can use slower-dissolving excipients elsewhere in the formulation while the active permeation enhancer works locally at the absorption interface
3Duration of action of moving object
If short acting APIs are used, then rapid therapeutic effect is achieved, but variability in absorption leads to inconsistent dosing
Solution Approach 1:
The acylated amino acid formulation creates a feedback mechanism where the enhanced and consistent absorption ensures that the short-acting peptide delivers its rapid therapeutic effect with predictable dosing. The formulation absorbs the variability that would otherwise affect the short-acting API, providing both speed and consistency
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The AC-aa-NS composition enhances bioavailability and absorption, reducing variability and providing a stable, effective oral delivery system for peptides and proteins, including therapeutic peptides and proteins, with improved half-life and reduced absorption window variability.
Implementation Method 1
The present invention concerns composition comprising a permeation enhancer, said permeation enhancer being an acylated aminoacid substituted on the amine function
Implementation Method 2
the applicant found an unexpected property of acylated aminoacid AC-aa-NS, or a salt thereof, as these compounds are protease inhibitors
Data Source
AI summary
The invention relates to a composition, in particular solid, comprising a permeation enhancer, said permeation enhancer being an acylated aminoacid substituted on the amine function, also called AC-aa-NS, said composition comprising in particular a peptide or a protein, the AC-aa-NS compounds, their methods of preparation and their use in medicine.