Bile Acid Sequestrant Compositions for Esophageal Disorder Treatment

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Solution Overview

Problem

Current treatments for bile reflux are often ineffective and difficult to distinguish from acid reflux, leading to ongoing inflammation and increased risk of esophageal complications such as GERD, Barrett's esophagus, and esophageal cancer, with existing medications like PPIs exhibiting inter-patient variability and significant drug interactions.

Innovation Solution

Compositions containing bile acid sequestrants like colesevelam, colesevelam hydrochloride, or colestipol, alone or in combination with proton pump inhibitors, are used to inhibit gastric and bile acid secretion, providing a therapeutic approach for esophageal disorders including GERD, heartburn, and esophageal adenocarcinoma, while protecting the esophageal lining from injury.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If proton pump inhibitors are used to treat acid reflux, then acid secretion is inhibited, but inter-patient variability and significant drug interactions occur reducing treatment reliability

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidinter-patient variability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces bile acid sequestrants as intermediary substances that bind to bile acids in the gastrointestinal tract, preventing their harmful effects on the esophageal lining. This mediator approach addresses the reliability issue by providing a mechanism that works independently of the variable proton pump inhibitor responses across different patients.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs composite treatment formulations containing both proton pump inhibitors and bile acid sequestrants. This composite approach combines two different mechanisms of action to overcome the limitations of using either agent alone, particularly addressing the inter-patient variability problem by providing multiple pathways for treatment effectiveness.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If existing medications are used to manage bile reflux, then some symptom relief is achieved, but neither solution is uniformly effective leading to ongoing inflammation

Engineering Contradiction:
Improvesymptom managementVSAvoiduniform effectiveness
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent extracts and specifically targets bile acids as the harmful component causing reflux-related damage. By using bile acid sequestrants that selectively bind to bile acids, the treatment removes the specific offending substance without requiring uniform response to broad-spectrum medications, thereby achieving more reliable and uniform effectiveness across patients.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the therapeutic parameter from general acid suppression to specific bile acid binding. This parameter change allows for more predictable and uniform treatment effectiveness by targeting the specific mechanism of bile acid-mediated esophageal injury rather than relying on variable responses to proton pump inhibition.

Inventive Principle:
Principle #35Parameter changes

3Loss of time

If bile and acid reflux are not effectively treated, then ongoing inflammation occurs, but distinguishing bile reflux from acid reflux is difficult leading to delayed appropriate treatment

Engineering Contradiction:
Improvetime to diagnosisVSAvoiddifferentiation accuracy
Core Design Contradiction:
Loss of timeVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the treatment approach by introducing bile acid sequestrants as a distinct therapeutic category separate from proton pump inhibitors. This segmentation allows clinicians to target bile acid-specific pathology with a mechanism that is fundamentally different from acid suppression, enabling more precise diagnosis and treatment selection even when clinical differentiation is challenging.

Inventive Principle:
Principle #1Segmentation

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

These compositions effectively treat and prevent esophageal disorders by reducing bile and acid reflux, providing sustained relief and protecting the esophageal lining, thereby addressing the limitations of existing treatments and improving patient outcomes.

Implementation Method 1

The active ingredient in the dosage form is a bile acid sequestrant... Bile acid sequestrants are compounds that bind to bile acids in the gastrointestinal tract

Methodology Applied
Scientific EffectIon Exchange: Ion Exchange

Implementation Method 2

a gastric-retention vehicle composition that contains one or more hydrogels such that the dosage form expands upon contact with gastric fluid

Methodology Applied
Scientific EffectHydrogel swelling: Hydrogel

Data Source

PatentEP2124884B1Compositions comprising bile acid sequestrants for treating esophageal disorders
Publication Date: 2019.07.10 IRONWOOD PHARMACEUTICALS INC

AI summary

Disclosed herein are novel compositions for treating or preventing upper GI tract disorders and protecting stratified squamous epithelium against injury by a noxious substance. The pharmaceutical composition comprises at least one bile acid sequestrant, alone or in combination with at least one proton pump inhibitor, and optionally one or more agent chosen from antacids, histamine H2-receptor antagonists, -aminobutyricacid-b (GABA-B) agonists,, prodrugs of GABA-B agonists, and protease inhibitors.