Hypnotic Agent Combination for Sleep Quality and Maintenance

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Solution Overview

Problem

Current treatments for insomnia and obstructive sleep apnea often come with significant side effects and limited efficacy, with short-acting hypnotic agents primarily inducing sleep but risking next-day dysfunction, and long-acting agents struggling to enhance slow-wave sleep, which is crucial for restorative sleep and daytime function.

Innovation Solution

A combination of short-acting and long-acting hypnotic agents with a sleep aid, formulated for immediate or delayed release, that includes specific compounds with structures allowing for synergistic effects on sleep quality and maintenance without negative impacts on waking phases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If short-acting hypnotic agents are used to induce sleep, then sleep onset is improved, but next-day dysfunction and daytime sedation occur

Engineering Contradiction:

Improvesleep onset inductionVSAvoidnext-day dysfunction

Core Design Contradiction:

Duration of action of moving objectVSObject-generated harmful factors

Solution Approach 1:

The patent combines short-acting hypnotic agents with long-acting hypnotic agents in a single formulation. The short-acting component addresses sleep onset while the long-acting component maintains sleep continuity and reduces awakenings, thereby eliminating the need for high doses of short-acting agents that cause next-day dysfunction.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent modifies the temporal profile of hypnotic agent delivery by using a combination of short- and long-acting agents with different half-lives. This parameter change in drug duration profile allows the short-acting agent to work during sleep onset without persisting into the next day, thus avoiding daytime sedation.

Inventive Principle:

Principle #35Parameter changes

2Duration of action of stationary object

If long-acting hypnotic agents are used to enhance slow-wave sleep, then sleep maintenance is improved, but efficacy in enhancing restorative sleep is limited

Engineering Contradiction:

Improvesleep maintenanceVSAvoidefficacy in enhancing slow-wave sleep

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent merges long-acting hypnotic agents with specific 5HT2A receptor antagonists. The long-acting agent provides sustained sleep maintenance while the 5HT2A antagonist selectively enhances slow-wave sleep architecture, creating a synergistic effect that improves both duration and quality of sleep.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a composite pharmacological formulation combining hypnotic agents with 5HT2A receptor antagonists. This composite approach leverages the different mechanisms of action to achieve both prolonged sleep maintenance and enhanced slow-wave sleep, addressing the limitations of single-agent therapies.

Inventive Principle:

Principle #40Composite materials

3Object-affected harmful factors

If benzodiazepines are used to treat insomnia, then sedation effect is improved, but adverse effects including cognitive impairment and motor coordination loss occur

Engineering Contradiction:

Improvesedation effectVSAvoidcognitive impairment

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent replaces long-acting benzodiazepines with a combination of short-acting hypnotic agents and 5HT2A receptor antagonists. This substitution uses shorter-acting compounds that provide necessary sedation during sleep without persisting into daytime hours, thus avoiding cognitive impairment and motor coordination loss.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the pharmacokinetic parameters of the treatment regimen by using agents with shorter half-lives and different mechanisms of action. This parameter change in drug duration and mechanism reduces the accumulation effect that causes daytime cognitive impairment while maintaining adequate nighttime sedation.

Inventive Principle:

Principle #35Parameter changes

4Reliability

If pharmacological agents are used to treat obstructive sleep apnea, then ventilatory support is improved, but ventilatory depressant action and other side effects occur

Engineering Contradiction:

Improveventilatory supportVSAvoidventilatory depressant action

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent utilizes 5HT2A receptor antagonists, which have been shown to have ventilatory stimulant effects, to treat obstructive sleep apnea. This converts the potential harmful effect of respiratory depression into a beneficial ventilatory support effect, while the hypnotic component addresses sleep maintenance.

Inventive Principle:

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

Data Source

PatentEP1928442B1Combination of a hypnotic agent and substituted bis aryl and heteroaryl compound and therapeutic application thereof

Publication Date: 2009.11.04 AVENTIS PHARMACEUTICALS INC

AI summary

The invention concerns the combination of a short-acting hypnotic agent and a compound of formula (I). Wherein X,Y,Z,A,B,D,Ar, R1 and R2 are as defined herein. The combination of this invention is useful in treating a variety of sleep disorders.