Peptide–Surfactant Compositions for Membrane Permeability and Absorption
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Solution Overview
Problem
Existing methods to enhance the membrane permeability and absorbability of peptide compounds, such as those containing N-substituted amino acid residues or combined with surfactants like lauroylcarnitine, have not been effectively addressed, particularly for peptide compounds with specific ClogP and solubility characteristics.
Innovation Solution
A composition comprising a peptide compound with ClogP between 4 and 25 and a surfactant with a carnitine residue, optionally including a solubility improver, enhances membrane permeability and absorbability by using a peptide compound with 9 to 15 amino acid residues and a surfactant like lauroyl-L-carnitine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the molecular weight of peptide compounds is increased to achieve desired pharmacological effects, then the therapeutic function is improved, but membrane permeability and absorbability deteriorate
Solution Approach 1:
The patent introduces lauroyl-L-carnitine as a surfactant intermediary that mediates between the peptide compound and biological membranes. This surfactant forms mixed micelles with the peptide, facilitating its transport across membranes without requiring structural modification of the peptide itself, thus resolving the contradiction between maintaining therapeutic function and improving permeability
Solution Approach 2:
The patent changes the physical-chemical parameters of the peptide compound by controlling its ClogP value (lipophilicity) within a specific range and adjusting its solubility characteristics. These parameter modifications enable the peptide to achieve both desired therapeutic function and improved membrane permeability when combined with the surfactant system
2Reliability
If the molecular weight of peptide compounds is increased to achieve desired pharmacological effects, then the therapeutic function is improved, but absorbability deteriorates
Solution Approach 1:
Lauroyl-L-carnitine serves as an absorption-promoting intermediary that forms complexes with medium molecular weight peptide compounds. This surfactant-peptide complex enhances intestinal absorbability through mechanisms such as micelle formation and interaction with transport proteins, allowing peptides with molecular weights of 500-2000 g/mol to achieve adequate absorption
Solution Approach 2:
The patent creates a composite system consisting of the peptide compound and surfactant in specific ratios. This composite formulation combines the therapeutic properties of the peptide with the absorption-enhancing properties of the surfactant, achieving both high therapeutic function and improved absorbability
3Object-affected harmful factors
If the structure of peptide compound is modified to improve membrane permeability, then membrane permeability is improved, but the function of peptide compound deteriorates
Solution Approach 1:
Instead of modifying the peptide structure directly, the patent uses lauroyl-L-carnitine as a structural intermediary that temporarily associates with the peptide during absorption. This approach improves membrane permeability while preserving the native structure and binding ability of the peptide to its target protein
Solution Approach 2:
The patent segments the absorption function from the therapeutic function by using a separate surfactant component for permeability enhancement. The peptide compound itself remains structurally intact for its therapeutic role, while the surfactant handles the permeability challenge, resolving the contradiction between structural modification and functional preservation
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 composition significantly improves the membrane permeability and absorbability of peptide compounds, as demonstrated by increased Caco-2 Papp values and solubility in phosphate buffer, facilitating better pharmaceutical applications.
Implementation Method 1
a surfactant having a carnitine residue, wherein the surfactant is lauroyl-L-carnitine
Data Source
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AI summary
[Problem to be Solved] To provide a composition containing a peptide compound and a surfactant, having enhanced membrane permeability and/or absorbability of the peptide compound. [Solution] A composition containing components (1) and (2) below: (1) at least one or more peptide compounds selected from the group consisting of (i), (ii), and (iii) below: (i) a peptide compound containing one or more N-substituted amino acid residues, (ii) a peptide compound having ClogP between 4 and 25, and (iii) a peptide compound having a solubility of 10,000 µg/mL or less and exceeds 0 µg/mL in 50 mM phosphate buffer (pH 6.5) under the conditions of 37°C, 1 atm; and (2) at least one or more surfactants selected from the group consisting of (iv) and (v) below: (iv) a surfactant having a linear alkylene structure and having carbon atoms between 5 and 13 in the linear alkylene structure, and (v) a surfactant having a carnitine residue.