GUCY2C Agonist and SCFA Composition to Reduce GI Side Effects
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Solution Overview
Problem
Current treatments for colorectal tumorigenesis, carcinogenesis, chronic intestinal inflammation, and cystic fibrosis-related gastrointestinal manifestations have limited efficacy and are associated with significant side effects, particularly diarrhea and dehydration, necessitating a more effective and side-effect-reduced therapeutic approach.
Innovation Solution
A pharmaceutical composition combining a guanylate cyclase C (GUCY2C) agonist with a short-chain C2 to C5 fatty acid or its salt or prodrug, administered in a therapeutically effective amount, to synergistically prevent and treat these conditions while reducing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a GUCY2C agonist is administered to treat colorectal tumorigenesis and chronic intestinal inflammation, then therapeutic efficacy is improved, but side effects such as diarrhea and dehydration increase
Solution Approach 1:
The patent combines a GUCY2C agonist with a short-chain fatty acid (SCFA) or its salt/prodrug into a single pharmaceutical composition. This merging of two therapeutic agents allows the SCFA to counteract the diarrhea-induced by the GUCY2C agonist through its independent mechanism of action on colonic epithelial cells, thereby maintaining therapeutic efficacy while reducing harmful side effects
Solution Approach 2:
The short-chain fatty acid acts as an intermediary substance that mediates between the GUCY2C agonist's therapeutic effect and its harmful side effects. The SCFA provides a protective effect on the intestinal mucosa and regulates colonic function, thereby mitigating the diarrhea and dehydration caused by the GUCY2C agonist without interfering with its antitumorigenic and anti-inflammatory actions
2Reliability
If dietary fiber is supplemented to provide butyrate, then CRC prevention is improved, but effects diverge due to different fiber types and gut microbiota composition
Solution Approach 1:
The patent changes the parameter of butyrate delivery from indirect (via fiber fermentation dependent on microbiota) to direct (via SCFA supplementation). This parameter change ensures consistent butyrate levels in the colon regardless of individual variations in gut microbiota composition or fiber type, providing reliable and reproducible CRC prevention effects
Solution Approach 2:
The patent extracts the active beneficial component (butyrate/SCFA) from the complex fiber fermentation process and delivers it directly. This extraction eliminates the variability introduced by different fiber types and microbiota compositions, ensuring consistent therapeutic effects while maintaining the core benefit of butyrate-mediated CRC prevention
Data Source
AI summary
A pharmaceutical composition includes a combination of a guanylate cyclase C (GUCY2C) agonist and a short-chain C2 to C5 fatty acid and/or a salt and/or a prodrug thereof in a therapeutically effective amount and one or more pharmaceutically acceptable excipients as well as to a method of preventing and/or treating colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations by administering to a patient, who has developed or is at risk to develop colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations, a therapeutically effective amount of a combination of a GUCY2C agonist and a short-chain C2 to C5 fatty acid or a salt or a prodrug thereof.