Cannabinoid Compositions Counteract Bile Acid-Induced DNA Damage
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Solution Overview
Problem
Current therapies are inadequate for suppressing malignant transformation and development of esophageal adenocarcinoma (EAC) associated with acid-biliary reflux, as bile acids like deoxycholic acid induce DNA damage and oxidative stress in esophageal cells.
Innovation Solution
A pharmaceutical composition comprising a cannabinoid represented by Formula (I) combined with a compound of Formula (II) or a terpene, such as cannabigerol (CBG) and phytol, is administered to counteract deoxycholic acid-mediated mitochondrial and DNA damage, reduce cell proliferation, and mitigate reactive oxygen species in esophageal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If bile acids like deoxycholic acid are present in refluxate, then gastroesophageal reflux disorder (GERD) and Barrett's Esophagus conditions occur, but DNA damage and oxidative stress are induced in esophageal cells
Solution Approach 1:
The patent applies this principle by using deoxycholic acid (a harmful substance) in a controlled in vitro system to study its effects, while simultaneously developing cannabinoid compositions that counteract its harmful effects. The harmful bile acid exposure is converted into a research opportunity to identify protective therapeutic agents.
Solution Approach 2:
The patent introduces cannabinoid compositions as intermediary substances that mediate between the harmful bile acids and esophageal cells. These cannabinoids act as protective intermediaries that reduce DNA damage and oxidative stress caused by bile acid exposure.
2Reliability
If current therapies are used for GERD and Barrett's Esophagus, then some symptoms may be managed, but malignant transformation and development of esophageal adenocarcinoma are not effectively suppressed
Solution Approach 1:
The patent applies parameter changes by modifying the chemical composition parameters of therapeutic agents. Specifically, it uses cannabinoid compositions with specific molecular structures (Formula I) and combinations (Formulas II and III) that have demonstrated efficacy in preventing malignant transformation, thereby changing the pharmacological parameters of available therapies.
3Productivity
If deoxycholic acid is exposed to esophageal cells, then cellular proliferation may be stimulated, but mitochondrial damage and DNA double-strand breaks occur
Solution Approach 1:
The patent applies preliminary anti-action by administering cannabinoid compositions before or during bile acid exposure to prevent mitochondrial damage and DNA breaks. The cannabinoids act in advance to protect cellular structures from the harmful effects of deoxycholic acid, countering the damage before it fully manifests.
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 effectively reverses mitochondrial depolarization, DNA damage, and oxidative stress induced by deoxycholic acid, thereby reducing the risk of esophageal adenocarcinoma development and associated conditions like Barrett's Esophagus and GERD.
Implementation Method 1
bile acids, such as deoxycholic acid (DCA), enter the esophagus during an episode of reflux, and are thought to promote cancer development. Patients with GERD and BE show high concentrations of DCA in their refluxate, which has cytotoxic effects and can induce DNA damage through a process that involves induction of reactive oxygen species (ROS)
Data Source
AI summary
Compositions comprising a cannabinoid and other compounds, such as terpenes, and methods of using such compositions. The disclosed compositions can be useful in, for example, treating and preventing esophageal adenocarcinoma and related diseases such as esophageal dysplasia, esophageal metaplasia, Barrett's Esophagus, gastroesophageal reflux disorder (GERD), or conditions associated with acid-biliary reflux.