Nu-8 Antimicrobial Compound pH Adaptability
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Solution Overview
Problem
Current antimicrobial compounds, such as Bisphosphocin compounds, are less effective at higher pH levels and can cause contact irritation in topical, inhalation, or intravesical administration routes, limiting their use in treating infections like diabetic foot ulcers, urinary tract infections, and lung infections.
Innovation Solution
A novel compound, sodium ((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-((butoxyoxidophosphor-yl)oxy)tetrahydrofuran-2-yl)methyl butyl phosphate, or Nu-8, which is more potent at higher pH levels and compatible with topical, inhalation, and intravesical administration, effectively targeting slow growth bacteria and maintaining stability against nuclease degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antimicrobial compounds (such as Bisphosphocin compounds) are used, then antimicrobial activity is achieved, but biological activity decreases at higher pH levels
Solution Approach 1:
The patent modifies the chemical structure of antimicrobial compounds by incorporating specific functional groups (amino or guanidino groups) that change their ionization state based on pH levels. This allows the compound to maintain positive charge and antimicrobial activity across a broader pH range, particularly at higher pH levels where conventional compounds fail.
2Reliability
If antimicrobial compounds are formulated at lower pH levels (below pH 3) to enhance activity, then biological activity is improved, but contact irritation occurs in topical, inhalation, or intravesical administration
Solution Approach 1:
The compound's pKa is engineered to allow it to remain positively charged and active at higher pH levels (above pH 3), eliminating the need to formulate at low pH. This pH optimization maintains antimicrobial efficacy while avoiding tissue irritation associated with acidic formulations.
3Duration of action of moving object
If conventional antimicrobial compounds are used, then treatment of infections is achieved, but prolonged exposure is limited due to irritation concerns
Solution Approach 1:
By designing the compound to maintain stability and antimicrobial activity at physiological pH levels, the patent enables prolonged exposure durations without the irritation limitations that constrain conventional compounds. The pH-resilient structure allows continuous therapeutic effect over extended periods.
Data Source
AI summary
Antimicrobial compounds and compositions of Formulas (I) to (III) and methods of use are disclosed. Another aspect of the present disclosure provides a pharmaceutical composition comprising a compound according to Formula (I) to (III), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents. Another aspect of the present disclosure provides a method of treating a bacterial infection in a patient in need thereof, the method comprising administering an effective amount of a compound according to Formula (I) to (III), or a pharmaceutically acceptable salt thereof, to the patient.