Ketone Ester Administration for CNS Oxygen Toxicity Seizure Prevention

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Solution Overview

Problem

Current methods for preventing central nervous system oxygen toxicity (CNS-OT) seizures are ineffective, as they lack a reliable mitigation strategy, and existing treatments like ketogenic diets and ketone supplements fail to provide sustained therapeutic ketosis, leading to incomplete seizure prevention.

Innovation Solution

Administration of R,S-1,3-butanediol acetoacetate diester (BD-AcAc2), a ketone ester, which induces rapid and sustained elevation of blood ketones, specifically acetoacetate and acetone, delaying the onset of CNS-OT seizures by mimicking the metabolic effects of starvation or a ketogenic diet without the dietary restrictions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ketogenic diets or ketone supplements are used to prevent CNS-OT seizures, then seizure prevention is improved, but the duration of therapeutic ketosis is insufficient

Engineering Contradiction:

Improveseizure prevention effectivenessVSAvoidduration of therapeutic ketosis

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The invention changes the chemical parameter of ketone administration by using ketone esters (specifically R,S-1,3-butanediol acetoacetate diester) instead of traditional ketone supplements. This chemical form transformation enables sustained release of ketone bodies, maintaining therapeutic ketosis levels for several hours and providing reliable seizure prevention during hyperbaric oxygen exposure

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The ketone ester is administered before hyperbaric oxygen exposure to pre-establish therapeutic ketosis. This preliminary action ensures that ketone bodies are already elevated in the blood before the oxidative stress of HBO2 begins, providing immediate protective effect that lasts throughout the exposure period

Inventive Principle:

Principle #10Preliminary action

2Reliability

If starvation or ketogenic diet is used to induce ketosis, then seizure protection is achieved, but the method is impractical for clinical application

Engineering Contradiction:

Improveseizure protectionVSAvoidpracticality of administration

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The ketone ester serves as an intermediary substance that bridges the gap between starvation-induced ketosis and practical clinical application. It is metabolized to produce ketone bodies (acetoacetate and acetone) in the same way starvation does, but without requiring dietary restriction or prolonged fasting, making it easy to administer and suitable for clinical use

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces the mechanical/behavioral system of dietary restriction and starvation with a chemical system (ketone ester administration). This substitution maintains the metabolic effect of ketosis while eliminating the practical difficulties of implementing starvation or ketogenic diets in clinical settings

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Power

If hyperbaric oxygen therapy is administered at high pressure, then therapeutic benefit is increased, but the risk of CNS-OT seizures increases

Engineering Contradiction:

Improvetherapeutic benefit of HBO2VSAvoidCNS-OT seizure risk

Core Design Contradiction:

PowerVSObject-affected harmful factors

Solution Approach 1:

The ketone ester is administered before hyperbaric oxygen exposure to pre-establish a protective metabolic state. This preliminary anti-action creates resistance to the harmful effects of high-pressure oxygen by shifting brain metabolism to ketone utilization, which is more resistant to oxidative stress, thereby allowing safe administration of high-pressure HBO2 therapy

Inventive Principle:

Principle #9Preliminary anti-action

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 ketone ester significantly delays the latency to seizure by 574% compared to controls, providing a novel therapeutic strategy for CNS-OT and seizure disorders by maintaining elevated ketone levels for several hours, effectively preventing seizures in rats exposed to hyperbaric oxygen.

Implementation Method 1

Administration of R,S-1,3-butanediol acetoacetate diester (BD-AcAc2), a ketone ester, which induces rapid and sustained elevation of blood ketones

Methodology Applied

Scientific EffectMetabolic conversion:

Data Source

PatentUS10842767B2Use of ketone esters for prevention of CNS oxygen toxicity

Publication Date: 2020.11.24 UNIV OF SOUTH FLORIDA

AI summary

The present invention demonstrates the therapeutic use of ketone esters for seizure disorders, Alzheimer's disease and malignant brain cancer, which are associated with metabolic dysregulation. The administration of ketone esters resulted therapeutic ketosis and neuroprotection against seizures resulting from CNS oxygen toxicity. Supplemental ketones were also found to reduce superoxide production in cultured cortex neurons exposed to hyperbaric oxygen and Aβ-42, and to decrease proliferation and viability in U87 glioma cells. These observations support the therapeutic effect of ketones for seizure disorders, Alzheimer's disease and malignant brain cancer. The ketone esters may be derived from acetoacetate and can include R,S-1,3-butanediol acetoacetate monoester, R,S-1,3-butanediol acetoacetate diester, or a combination of the two.