Peptide Tight Junction Antagonists for Tissue Permeability Control
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Solution Overview
Problem
Current treatments for conditions characterized by excessive or undesirable permeability of tissues containing tight junctions, such as autoimmune diseases and inflammatory bowel diseases, lack effective solutions to manage and prevent tissue permeability issues.
Innovation Solution
Development of peptide tight junction antagonists that can bind to specific receptors to inhibit the opening of tight junctions, thereby reducing permeability and addressing conditions like Celiac disease, inflammatory bowel diseases, and respiratory distress syndrome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If tight junctions are opened to increase permeability for therapeutic agent delivery, then absorption of drugs improves, but tissue barrier integrity is compromised leading to excessive permeability
Solution Approach 1:
The patent applies preliminary action by pre-administering tight junction opening agents (like ZOT or zonulin) before administering therapeutic agents. This temporary opening of tight junctions facilitates enhanced absorption of subsequently administered drugs, while the effect is transient and reversible, allowing barrier integrity to be restored afterward. This resolves the contradiction by achieving improved drug delivery without permanent compromise of tissue barrier function.
Solution Approach 2:
The patent employs periodic action through controlled, temporary opening of tight junctions using agents that induce transient permeability changes. The tight junctions are opened periodically to allow drug passage, then close to restore barrier function. This cyclical opening and closing mechanism enables repeated therapeutic agent delivery while maintaining overall tissue integrity between treatment periods.
2Adaptability or versatility
If tight junction permeability is increased to treat diseases like Celiac disease, then therapeutic access improves, but harmful factors can more easily penetrate tissues
Solution Approach 1:
The patent uses tight junction opening agents (ZOT, zonulin) as intermediaries that temporarily modify barrier permeability to allow therapeutic agent passage. These intermediaries act as controlled mediators that facilitate drug delivery while their effects are transient and reversible, preventing permanent compromise of barrier function that would otherwise allow harmful substances to penetrate.
Solution Approach 2:
The patent applies parameter changes by temporarily altering the permeability parameter of tight junctions through pharmacological agents. This dynamic modification allows the barrier to transition between closed (protective) and open (permeable) states, enabling therapeutic access when needed while maintaining protective function at other times, thus preventing continuous penetration of harmful factors.
Data Source
AI summary
The present invention provides novel peptides that inhibit and/or reduce the opening of mammalian tight junctions, i.e. peptide tight junction antagonists. The present invention also provides methods for the treatment of excessive or undesirable permeability of a tissue by administering to a subject suffering from such a condition a composition comprising a peptide tight junction antagonist of the invention.