GC-C Agonist Peptides for Opioid-Induced Bowel Dysfunction
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Solution Overview
Problem
Opioids used for pain management often cause debilitating adverse effects such as opioid-induced bowel dysfunction, respiratory depression, and esophageal dysfunction, for which effective treatments are lacking.
Innovation Solution
The use of guanylate cyclase C (GC-C) agonists, specifically peptides with defined amino acid sequences, to prevent or alleviate opioid-induced dysfunctions by enhancing fluid secretion and gastrointestinal motility, potentially combined with opioids and cGMP-dependent phosphodiesterase inhibitors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If opioids are administered for pain management, then pain relief is achieved, but opioid-induced bowel dysfunction and other adverse effects occur
Solution Approach 1:
The patent introduces GC-C agonists as intermediary substances that mediate between the harmful effects of opioids and the desired pain relief. The GC-C agonist acts as a separate therapeutic agent that counteracts opioid-induced bowel dysfunction through a different mechanism (guanylate cyclase activation) without interfering with opioid analgesic effects, thus resolving the contradiction by adding a mediator rather than modifying the opioid itself
Solution Approach 2:
The patent changes the therapeutic parameter by introducing a second agent (GC-C agonist) with different pharmacological properties. Instead of trying to modify opioid parameters to reduce side effects, the solution changes to a combination therapy where the GC-C agonist operates through a separate pathway (increasing cGMP, stimulating chloride secretion) to counteract bowel dysfunction while allowing opioid pain relief to continue
2Ease of operation
If conventional laxatives are used to treat opioid-induced constipation, then bowel movement is stimulated, but they are ineffective for severe cases
Solution Approach 1:
The patent changes the pharmacological parameter from conventional laxative mechanisms to GC-C agonist mechanism. The GC-C agonist works by activating guanylate cyclase C receptors, increasing intracellular cGMP, and stimulating chloride secretion through CFTR channels - a fundamentally different parameter pathway than conventional laxatives, which explains its superior effectiveness in severe cases while maintaining ease of administration
Solution Approach 2:
The patent segments the treatment approach by separating the pain management function (opioid) from the bowel dysfunction treatment function (GC-C agonist). This segmentation allows each agent to optimize its specific function without the limitations of conventional combined approaches, where the GC-C agonist specifically targets the bowel dysfunction pathway independent of opioid dosage
3Reliability
If GC-C agonists are combined with opioids, then bowel dysfunction is alleviated, but drug interaction complexity increases
Solution Approach 1:
The GC-C agonist serves as an intermediary therapeutic agent that bridges the gap between opioid administration and bowel function restoration. By acting through a completely different receptor system (GC-C rather than opioid receptors), it mediates bowel dysfunction relief without complex pharmacokinetic interactions, simplifying the combination therapy compared to agents that might compete for the same metabolic pathways
Solution Approach 2:
The patent extracts the bowel dysfunction treatment function from the opioid therapy itself, creating a separate, independent therapeutic pathway. The GC-C agonist is extracted as a distinct agent with its own mechanism of action, allowing it to be added to the regimen without complicating the opioid's primary pain relief function, thus managing complexity by separation rather than integration
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 GC-C agonists effectively alleviate opioid-induced bowel dysfunction by stimulating chloride currents and activating PKG-II, leading to improved gastrointestinal transit and fecal output, while also being compatible with opioid administration.
Implementation Method 1
guanylate cyclase C (GC-C) agonists, specifically peptides with defined amino acid sequences, to prevent or alleviate opioid-induced dysfunctions by enhancing fluid secretion and gastrointestinal motility
Implementation Method 2
The GC-C agonists effectively alleviate opioid-induced bowel dysfunction by stimulating chloride currents and activating PKG-II
Implementation Method 3
The composition may further comprise an opioid and/or a cGMP-dependent phosphodiesterase inhibitor
Data Source
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Figure 3A~3B
AI summary
This invention provides a method to prevent, control, and/or treat opioid induced dysfunctions comprising administering to a patient in need a guanylate cyclase receptor agonist (GCRA) peptide. Compositions comprising guanylate cyclase receptor agonist (GCRA) peptides, methods of making, and methods of treatment are also disclosed.