Nitrosylated Propanediol Compositions for Stable NO Delivery
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Solution Overview
Problem
Current methods for preparing nitric oxide (NO)-delivering compounds face issues such as undesired side-effects, impurities, degradation, and inefficiencies, particularly in the preparation and administration of organic nitrites, leading to complications like methemoglobin production and complex handling requirements.
Innovation Solution
A process involving the reaction of propanediols with a source of nitrite in specific solvent conditions, either organic or bi-phasic, to produce mono- and bis-nitrosylated propanediols, minimizing impurities and enabling stable, non-aqueous compositions for convenient handling and administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to prepare organic nitrites, then nitric oxide delivering compounds can be obtained, but undesired side effects occur including methemoglobin production and impurities
Solution Approach 1:
The patent changes the chemical structure parameters by introducing a propanediol backbone with specific hydroxyl group positions, and controls the degree of nitrosylation (mono- or bis-nitrosylated) to optimize therapeutic safety. This structural parameter change eliminates the harmful methemoglobin production while maintaining NO-delivering capability
Solution Approach 2:
The patent converts the potential harm of nitrite-based synthesis into a benefit by carefully controlling the reaction conditions and selecting specific propanediol isomers, transforming a method that traditionally produces impurities into one that yields high-purity, safe therapeutic compounds
2Ease of operation
If aqueous compositions are used for NO-delivering compounds, then administration is simplified, but storage and transportation require complex handling due to degradation
Solution Approach 1:
The patent changes the physical state parameter from aqueous to non-aqueous form, which fundamentally improves chemical stability during storage and transportation. The non-aqueous environment prevents hydrolysis and degradation while maintaining the compound's ability to deliver nitric oxide when administered
Solution Approach 2:
The patent creates a stable formulation that can be stored for extended periods without degradation, eliminating the need for complex cold chain storage or short shelf-life handling requirements
3Quantity of substance
If high concentrations of NO-delivering compounds are prepared, then therapeutic efficacy is improved, but handling and storage become more difficult
Solution Approach 1:
The patent changes the solvent system parameter to non-aqueous media, which enables the preparation of high-concentration stable formulations. This parameter change allows high concentrations to be achieved without the degradation and handling difficulties associated with traditional aqueous systems
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 process results in high-concentration, chemically stable compositions with reduced storage and transportation needs, minimizing side effects and facilitating safe, efficient therapeutic use.
Implementation Method 1
A process involving the reaction of propanediols with a source of nitrite in specific solvent conditions, either organic or bi-phasic, to produce mono- and bis-nitrosylated propanediols
Data Source
AI summary
Described is a process for the synthesis of mono- and bis-nitrosylated propanediols, as well as compositions and pharmaceutical formulations that includes the compounds. The process proceeds by reacting a corresponding propanediol that is not nitrosylated with a source of nitrite, optionally in the presence of a suitable acid. When the source of nitrite is an organic nitrite, reacting step is performed in a suitable organic solvent, and when the source of nitrite is an inorganic nitrite, the reacting step is performed in a bi-phasic solvent mixture comprising an aqueous phase and a non-aqueous phase. Also disclosed are methods of treating a condition wherein administration of nitric oxide (NO) has a beneficial effect by administering said compounds, compositions or formulations.