Modified Peptide Permeation Enhancer for Mucous Membranes
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current permeation enhancers for mucous membranes, such as peptides and proteins, face challenges with physicochemical stability and toxicity, and often require adjuvants or additives, limiting their effectiveness in enhancing drug bioavailability through mucous membrane permeability.
Innovation Solution
A peptide with an amino acid sequence of Phe-Cys-Ile-Gly-Arg-Leu, where the carboxyl group of Leucine at the terminal end is modified to -CONH2, acts as a permeation enhancer, opening tight junctions between mucous membrane cells to facilitate drug passage without the need for adjuvants or additives, thereby enhancing bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides or proteins are used as permeation enhancers to enhance mucous membrane permeability, then the permeation of drugs is improved, but the peptides or proteins display low physicochemical stability depending on pH value
Solution Approach 1:
The patent modifies the amino acid sequence parameters of the peptide, specifically incorporating amino acids with specific properties (e.g., Arginine at positions 3-5, Leucine at position 6) to optimize both stability across different pH values and permeation enhancement capability. The modified peptide sequence (e.g., FCIGRL) demonstrates improved physicochemical stability while maintaining permeation enhancer function.
2Reliability
If peptides or proteins are used as permeation enhancers, then the permeation of drugs is improved, but they are likely to be toxic to the cells
Solution Approach 1:
The patent applies local quality by modifying specific regions of the peptide molecule while maintaining the overall structure. The N-terminal region (Phe-Cys-Ile-Gly-Arg) and C-terminal region (Leu) are optimized with specific amino acid compositions that provide permeation enhancement while reducing cytotoxicity. The modified peptide shows reduced hemolysis and cell toxicity compared to conventional peptides.
3Reliability
If conventional peptides are used as permeation enhancers, then the permeation function is achieved, but adjuvants or additives like carrageenan are required, complicating the preparation
Solution Approach 1:
The patent extracts and eliminates the need for adjuvants and additives by incorporating all necessary functional properties directly into the peptide molecule itself. The modified peptide sequence (FCIGRL) provides both permeation enhancement and stability functions internally, removing the requirement for external stabilizers like carrageenan and simplifying the formulation to essentially just the peptide and drug.
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 modified peptide significantly increases the permeability of drugs through mucous membranes, including the nasal and small intestinal routes, leading to improved bioavailability and therapeutic effects of active components like insulin and paclitaxel.
Implementation Method 1
the permeation enhancer promotes the transfer of drugs passing through the paracellular route, that is, the intercellular space between the mucous membrane cells
Data Source
Figure 1
AI summary
The present invention modifies the carboxyl-terminal end of a peptide used as a permeation enhancer to enhance the function of the peptide to boost the mucous membrane permeation, thereby noticeably increasing the bioavailability of a drug that is administered together with the peptide.