IBAT Inhibitors for Targeted Bile Acid Reabsorption Control

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Solution Overview

Problem

Existing treatments for liver diseases related to high bile acid concentrations in serum and liver organs do not effectively address the underlying mechanism of bile acid re-absorption, leading to persistent liver damage.

Innovation Solution

Development of specific IBAT inhibitors, represented by compounds of formula (I), which block the ileal bile acid transporter mechanism to reduce bile acid concentrations in the liver and improve liver health by reducing serum amino transferases, hydroxyproline content, and infiltrating neutrophils and proliferating hepatocytes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If IBAT mechanism is blocked to reduce bile acid concentration, then liver function is improved, but bile acid re-absorption is inhibited

Engineering Contradiction:

Improveliver functionVSAvoidbile acid re-absorption

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of excessive bile acid re-absorption into a beneficial therapeutic effect by using IBAT inhibitors to block the transporter. This prevents harmful bile acid accumulation in the liver while maintaining physiological bile acid levels in the intestine through controlled inhibition, thus transforming a pathological process into a therapeutic mechanism

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the parameter of bile acid concentration by introducing IBAT inhibitors that specifically block the ileal bile acid transporter. This alters the bile acid re-absorption rate parameter, reducing hepatic bile acid concentration from pathological levels to therapeutic levels, thereby improving liver function without complete elimination of bile acid recycling

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If existing treatments are used for liver diseases, then some symptoms are relieved, but the underlying mechanism of bile acid re-absorption is not addressed

Engineering Contradiction:

Improveliver damageVSAvoidunderlying mechanism

Core Design Contradiction:

Object-affected harmful factorsVSLoss of information

Solution Approach 1:

The patent extracts and targets the specific underlying mechanism of bile acid re-absorption through the IBAT transporter, separating this pathogenic mechanism from other liver disease factors. By specifically inhibiting IBAT rather than using general liver protective agents, the treatment addresses the root cause of bile acid-mediated liver damage while maintaining other physiological functions

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces IBAT inhibitors as intermediary substances that specifically mediate between bile acid molecules and the IBAT transporter. These inhibitors bind to the transporter and prevent bile acid re-absorption without directly affecting hepatocytes or other liver components, thereby treating the underlying mechanism while preserving normal liver physiology

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250326789A1IBAT inhibitors for the treatment of liver diseases

Publication Date: 2025.10.23 ALBIREO

AI summary

The present invention regards specific IBAT inhibitors useful in the prophylaxis and/or treatment of a liver disease. It also relates to compositions comprising these IBAT inhibitors, a method for treatment of the disorders and a kit comprising the substances or the compositions.