Stiripentol for Hyperammonemia Treatment

Solution Overview

Problem

Current treatments for hyperammonemia, such as sodium phenylbutyrate and glycerol phenylbutyrate, require frequent administration and are associated with significant side effects, including nausea, vomiting, and the risk of overdosing, which can lead to serious metabolic side effects and death.

Innovation Solution

The compound stiripentol, or its pharmaceutically acceptable salt, hydrate, or solvate, is used to reduce methionine sulfoximine-induced hyperammonemia and associated seizures, potentially in combination with other drugs like sodium benzoate or lactulose, for the prevention or treatment of hyperammonemia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments such as sodium phenylbutyrate and glycerol phenylbutyrate are used to reduce ammonia levels, then hyperammonemia is treated, but frequent administration is required and significant side effects occur including nausea, vomiting, and risk of overdosing

Engineering Contradiction:

Improveeffectiveness of hyperammonemia treatmentVSAvoidfrequency of administration and side effects

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of existing phenylbutyrate derivatives to create stiripentol and related compounds. This structural modification changes the pharmacokinetic parameters of the drug, resulting in extended half-life and sustained ammonia-lowering effects that last throughout the dosing interval, thereby reducing administration frequency from multiple times daily to once daily or less frequent dosing

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention implements periodic action through the design of long-acting compounds that maintain therapeutic ammonia levels throughout extended dosing intervals. The modified compounds provide sustained drug action that covers the entire dosing period, eliminating the need for frequent re-administration while maintaining reliable hyperammonemia control

Inventive Principle:

Principle #19Periodic action

2Reliability

If current treatments are administered frequently to maintain ammonia control, then hyperammonemia is managed, but the risk of overdosing increases leading to serious metabolic side effects and death

Engineering Contradiction:

Improveammonia level controlVSAvoidrisk of overdosing and metabolic side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of existing phenylbutyrate derivatives to create stiripentol and related compounds. This structural modification changes the pharmacokinetic parameters of the drug, resulting in extended half-life and sustained ammonia-lowering effects that last throughout the dosing interval, thereby reducing administration frequency from multiple times daily to once daily or less frequent dosing

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention implements beforehand cushioning by designing compounds with extended half-life and sustained action that provide a buffer against ammonia level fluctuations. This pharmacokinetic cushioning effect maintains stable therapeutic levels throughout the dosing interval, preventing both under-dosing and overdosing scenarios that could lead to metabolic side effects or death

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS20240207221A1Treatment of hyperammonemia

Publication Date: 2024.06.27 BIOCODEX INC

AI summary

The present invention relates to a compound of the following formula (I):or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the prevention or treatment of hyperammonemia in an individual.