Organic Nitrite Stability via De-aeration and NO Saturation
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Solution Overview
Problem
Current NO-donating compounds, such as organic nitrites, face issues with stability, side effects, and tolerance development, particularly when administered as infusions, leading to problems like methemoglobin production and unsatisfactory storage properties due to impurities and degradation.
Innovation Solution
Development of novel organic nitrites with improved stability and storage forms, using de-aerated and NO-saturated vehicles to prevent decomposition, and formulation methods that maintain NO equilibrium, ensuring non-enzymatic release and reduced methemoglobin formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional organic nitrites are used as NO-donating compounds, then NO release is achieved, but stability and storage properties deteriorate due to impurities and degradation
Solution Approach 1:
The patent changes the chemical parameters of the organic nitrite compounds by introducing specific molecular structures (formula I and II) with improved stability. The compounds are synthesized through controlled reactions with specific reagents and conditions, creating nitrites that resist degradation and maintain stability during storage and administration.
Solution Approach 2:
The patent employs inert atmosphere techniques during synthesis and storage to prevent oxidation and degradation of the organic nitrites. The compounds are handled in oxygen-free environments, and the formulation includes measures to maintain an inert atmosphere throughout storage and administration, preventing unwanted chemical reactions.
2Reliability
If organic nitrites are administered as infusions, then therapeutic effect is achieved, but side effects and tolerance development increase
Solution Approach 1:
The patent converts the potentially harmful rapid release of NO into a beneficial controlled release mechanism. The novel organic nitrites are designed to release NO gradually and non-enzymatically, transforming the harmful effect of rapid NO release (which causes side effects) into a beneficial sustained release that maintains therapeutic levels without tolerance development.
Solution Approach 2:
The patent employs transient, short-lived organic nitrite compounds that rapidly decompose to release NO and then disappear from the system. This disposable approach ensures that the compounds provide therapeutic effect without accumulating or causing long-term side effects, as the compounds are metabolized and eliminated quickly.
3Stability of the object's composition
If de-aerated and NO-saturated vehicles are used, then storage stability is improved, but formulation complexity increases
Solution Approach 1:
The patent performs preliminary actions during formulation by pre-deaerating the vehicle and pre-saturating it with NO gas before adding the organic nitrite compound. This preliminary preparation prevents oxidation and degradation during storage, maintaining stability without requiring complex ongoing control systems.
Solution Approach 2:
The patent introduces NO gas as an intermediary substance that serves multiple functions: it saturates the vehicle to prevent oxidation, maintains equilibrium during storage, and ensures stable release during administration. This intermediary approach simplifies the overall formulation by using a single additive to achieve multiple stability goals.
Data Source
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AI summary
Organic nitrites can be produced from a compound which is a mono/polyhydric alcohol or an aldehyde- or ketone-derivate thereof after de-aeration of the same, using NO gas, and stored in an environment saturated with gaseous NO. Organic nitrites produced according to the invention exhibit less impurities and improved storage stability compared to conventionally produced nitrites. The organic nitrites of the invention can easily be formulated into pharmaceutical compositions and have utility for the treatment of various conditions.