Nitric Oxide Generating System for Tuberculosis Treatment
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Solution Overview
Problem
Current methods for generating and delivering nitric oxide for therapeutic use face challenges in efficient production and delivery, particularly at physiologically tolerable pH levels, leading to inadequate yields and skin irritation issues.
Innovation Solution
A nitric oxide generating system using a nitrite salt and a proton source, such as organic carboxylic or non-carboxylic acids, in the presence of organic polyols, which allows for nitric oxide production at higher pH levels (5-8), enhancing reaction output and delivery efficacy while minimizing skin irritation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If nitric oxide is generated using conventional acidification methods at low pH levels, then the reaction yield is improved, but skin irritation and tissue damage occur
Solution Approach 1:
The patent changes the pH parameter from conventional low pH (below 4) to a higher physiological range (pH 5-8), specifically using buffers at pH 5.2-5.8. This parameter change allows the nitric oxide generating system to maintain effective antibacterial activity against M. tuberculosis while avoiding skin irritation and tissue damage associated with low pH formulations
Solution Approach 2:
The patent introduces an intermediary buffering system (phosphate buffer, citrate buffer, or HEPES buffer) that mediates between the acidification reaction and the biological tissue. This intermediary maintains the pH within the tolerable range of 5.2-5.8, allowing nitric oxide generation to proceed effectively while protecting skin and tissues from harmful low pH effects
2Object-affected harmful factors
If nitric oxide is generated at higher pH levels (5-8) to reduce skin irritation, then the physiological tolerability is improved, but the reaction yield and delivery efficacy decrease
Solution Approach 1:
The patent optimizes multiple parameters simultaneously: pH (5.2-5.8), temperature (37°C), and component concentrations (nitrite salt 0.1-10 mM, acid 0.1-10 mM, polyol 1-50%). These coordinated parameter changes enable effective nitric oxide generation at higher pH levels that would otherwise be non-productive
Solution Approach 2:
The patent employs organic polyols (glycerol, propylene glycol, ethylene glycol) that serve multiple functions: they act as reducing agents to enhance nitric oxide generation, serve as cosolvents to improve delivery efficacy, and contribute to the overall stability of the formulation. This self-service approach enables the system to maintain high productivity at physiological pH
3Ease of manufacture
If conventional nitric oxide generating systems are used, then the production process is simple, but the delivery period is short and therapeutic efficacy is limited
Solution Approach 1:
The patent creates a continuous nitric oxide generating system where the buffered acidification reaction proceeds steadily over an extended period. The buffering capacity maintains stable pH conditions that sustain the reaction, while organic polyols continuously reduce nitrite to nitric oxide, providing prolonged therapeutic action rather than a brief burst
Solution Approach 2:
The patent uses a composite formulation combining nitrite salt, organic acid, buffering agents (phosphate, citrate, or HEPES), and organic polyols. This composite material integrates multiple functional components that work synergistically to extend the delivery period while maintaining production simplicity and therapeutic efficacy
4Adaptability or versatility
If nitric oxide generating compositions are formulated for broad spectrum antimicrobial activity, then the versatility against multiple pathogens is improved, but the formulation complexity increases
Solution Approach 1:
The patent creates a universal nitric oxide generating formulation that functions against multiple pathogen types (bacteria including M. tuberculosis, viruses, fungi, and parasites) through a single mechanism. The core components (nitrite salt, organic acid, buffer, polyol) work together to generate nitric oxide, which provides broad-spectrum antimicrobial activity without requiring separate formulations for different pathogens
Solution Approach 2:
The patent optimizes the pH parameter to the physiological range of 5.2-5.8, which creates an environment that is both safe for human tissues and effective against diverse pathogens. This parameter optimization enables the formulation to maintain simplicity while achieving broad spectrum activity, as the same pH-optimized composition effectively targets multiple pathogen types
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 system achieves enhanced nitric oxide production and extended delivery periods, providing effective antimicrobial activity against M. tuberculosis and other pathogens, including viral and fungal infections, with reduced skin irritation and improved therapeutic applications.
Implementation Method 1
a nitrite salt and a proton source comprising one or more acid selected from organic carboxylic acids and organic non-carboxylic acids
Implementation Method 2
the antibacterial effect against M. tuberculosis can be enhanced if the NO generating composition is prepared
Implementation Method 3
The NO generating system may comprise one or more organic polyol
Implementation Method 4
the acid serving as proton source for the generation of nitric oxide can be effective when buffered to a relatively high pH, for example a pH between about 5 and about 8
Implementation Method 5
Nitric oxide and NO generating compositions have a range of antimicrobial and other advantageous physiological activities
Data Source
AI summary
The invention provides one or more agent selected from nitric oxide (NO), a nitric oxide generating composition, a combination or combinable association of ingredients for a nitric oxide generating composition, and mixtures thereof, for use as an antibacterial agent against tuberculosis and Mycobacterium tuberculosis.