Edaravone Borneol Composition ALS Treatment Synergy

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Solution Overview

Problem

Current treatments for amyotrophic lateral sclerosis (ALS) do not effectively address the progressive muscular atrophy and respiratory failure associated with the disease, with existing therapies showing limited efficacy in clinical trials.

Innovation Solution

A composition comprising 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) and natural borneol, in a specific mass ratio, is used to treat ALS, potentially offering synergistic benefits in improving motor function, survival time, and memory impairment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If edaravone is used alone to treat ALS, then it provides free-radical scavenging effects, but clinical trials show it does not significantly improve ALSFRS-R scores or reach primary endpoints

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidclinical trial success rate
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent combines edaravone with borneol to create a composite therapeutic formulation. This merging of two distinct compounds with different mechanisms of action (edaravone for free-radical scavenging and borneol for neuroprotection and anti-excitotoxicity) aims to overcome the limitations of edaravone monotherapy and achieve synergistic therapeutic effects in ALS treatment.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite pharmaceutical composition consisting of edaravone and borneol. This composite approach integrates multiple active ingredients that target different pathological pathways in ALS, including oxidative stress, excitotoxicity, and neuronal protection, thereby enhancing overall therapeutic efficacy compared to single-agent therapy.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If borneol is used to improve intestinal absorption and blood-brain barrier permeability, then it enhances drug delivery, but its individual neuroprotective effects are insufficient for ALS treatment

Engineering Contradiction:
Improvedrug absorptionVSAvoidtherapeutic efficacy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

Borneol serves as an intermediary substance that facilitates the delivery of edaravone to the central nervous system by improving intestinal absorption and blood-brain barrier permeability. Simultaneously, borneol provides complementary neuroprotective effects, creating a dual-function formulation that addresses both drug delivery and therapeutic efficacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If the composition of edaravone and borneol is used, then synergistic effects are achieved in extending survival time and improving motor function, but the device complexity increases

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent optimizes the formulation by establishing specific mass ratio parameters (1:4 to 4:1, preferably 1:2 to 2:1) for edaravone and borneol. This parameter optimization ensures synergistic therapeutic effects while maintaining formulation simplicity and manufacturability, balancing efficacy with practical considerations.

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 composition significantly extends survival time and improves motor function in transgenic mice models of ALS, demonstrating superior efficacy compared to edaravone or borneol alone, with a synergistic effect confirmed by statistical analysis.

Implementation Method 1

3-methyl-l-phenyl-2-pyrazolin-5-one (edaravone), as a new potent free-radical scavenger, may scavenge hydroxyl radical (OH), nitric oxide radical (NO·), peroxynitrite ion (ONOO-)

Methodology Applied
Scientific EffectFree-radical scavenging: Oxidation

Implementation Method 2

borneol is capable of improving intestinal absorption, blood-brain barrier

Methodology Applied
Scientific EffectPermeability enhancement: Permeation

Data Source

PatentEP3308783B1Edaravone and borneol for treating amyotrophic lateral sclerosis
Publication Date: 2021.03.03 JIANGSU SIMCERE PHARMA CO LTD
  • EP3308783B1 patent drawingFigure 1~2
  • EP3308783B1 patent drawingFigure 3~4
  • EP3308783B1 patent drawingFigure 5~6

AI summary

The present invention relates to the use of a composition for preparing a medicament for the treatment of amyotrophic lateral sclerosis and associated disorders. The composition comprises 3-methyl-1-phenyl-2-pyrazoline-5-one or pharmaceutically acceptable salts thereof and borneol. The medicament is a drug used for delaying the occurrence time of amyotrophic lateral sclerosis and extending the survival time, and for improving memory function defect of amyotrophic lateral sclerosis.