Morphinan Derivative Inhibits Sphincter of Oddi Contraction

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Solution Overview

Problem

Current therapeutic agents for biliary tract diseases, particularly those involving sphincter of Oddi contraction, lack effectiveness and often exacerbate conditions due to opioid receptor agonist activities, and there is a need for a compound with morphinan skeleton that inhibits sphincter of Oddi contraction.

Innovation Solution

A therapeutic or prophylactic agent comprising a morphinan derivative or its pharmaceutically acceptable acid addition salt, specifically (−)-17-(cyclopropylmethyl)-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan, which inhibits sphincter of Oddi contraction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If opioids are used to treat biliary tract diseases, then pain relief is achieved, but sphincter of Oddi contraction is exacerbated

Engineering Contradiction:

Improvepain relief effectivenessVSAvoidsphincter of Oddi contraction

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful μ-opioid receptor agonist activity into a beneficial effect by designing compounds that selectively activate κ-opioid receptors. This selective activation achieves the desired therapeutic effect (inhibition of sphincter of Oddi contraction and pain relief) while avoiding the harmful side effect (exacerbation of biliary tract diseases) associated with μ-opioid receptor activation.

Inventive Principle:

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

2Reliability

If conventional therapeutic agents are used to inhibit sphincter of Oddi contraction, then biliary tract disease symptoms are alleviated, but effectiveness is insufficient

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment efficacy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent changes the pharmacological parameter by introducing a novel mechanism of action through κ-opioid receptor agonism. This parameter change (selective κ-receptor activation) differentiates the invention from conventional agents and achieves superior therapeutic effectiveness in treating biliary tract diseases by directly addressing the underlying pathophysiology of sphincter of Oddi dysfunction.

Inventive Principle:

Principle #35Parameter changes

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 agent effectively inhibits sphincter of Oddi contraction, providing a therapeutic or prophylactic effect on biliary tract diseases such as biliary obstruction, gallbladder disorder, and primary biliary cirrhosis, as demonstrated by reduced perfusion pressure in rabbit models.

Implementation Method 1

Morphinan derivatives and pharmaceutically acceptable acid addition salts thereof, with their κ opioid receptor agonist activity

Methodology Applied

Scientific EffectOpioid receptor agonist activity:

Data Source

PatentUS10131672B2Therapeutic or prophylactic agent for biliary diseases

Publication Date: 2018.11.20 TORAY INDUSTRIES INC

AI summary

A therapeutic or prophylactic agent for biliary tract diseases includes as an effective component a specific compound having a morphinan skeleton represented by Compound 1, or a pharmaceutically acceptable acid addition salt thereof: