Buffer Solutions with Extreme pH for Selective Bactericidal Activity
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Solution Overview
Problem
Conventional buffer solutions used to maintain pH for pharmaceutical agents often foster microbial growth, particularly gram-negative bacteria, leading to sepsis and infection-related complications, as they are difficult to eradicate and control, especially in hospital environments.
Innovation Solution
A buffer system with a pH of greater than about 10 or less than about 4.5 and low buffer capacity, comprising glycine and sodium hydroxide or sorbic/citric acid, is used to selectively kill gram-negative bacteria and inhibit the growth of gram-positive bacteria and fungi, suitable for pharmaceutical preparations like treprostinil sodium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional buffer solutions with neutral pH are used to maintain pH for pharmaceutical agents, then pH stability is improved, but microbial growth is fostered leading to sepsis and infection-related complications
Solution Approach 1:
The patent applies parameter changes by adjusting the buffer pH to extreme values (greater than 10 or less than 4.5) rather than maintaining neutral pH. This parameter change creates an environment that is bactericidal to gram-negative bacteria while remaining bacteriostatic to gram-positive bacteria, thus resolving the contradiction between pH stability and microbial growth prevention
Solution Approach 2:
The patent converts the harmful effect of extreme pH (which would normally be detrimental to pharmaceutical stability) into a beneficial antimicrobial property. The extreme pH conditions that would typically be considered harmful are specifically selected to exhibit selective bactericidal activity against gram-negative bacteria, transforming a potential harm into a therapeutic benefit
2Stability of the object's composition
If buffer capacity is increased to maintain pH stability, then pH control is improved, but selective bactericidal activity against gram negative bacteria is reduced
Solution Approach 1:
The patent applies parameter changes by deliberately reducing buffer capacity while maintaining extreme pH values. This creates a unique condition where the pH remains stable enough to maintain selectivity for gram-negative bacteria but with low enough buffer capacity to allow the pH to fluctuate sufficiently to exert bactericidal pressure on these organisms
3Object-affected harmful factors
If extreme pH buffers (greater than 10 or less than 4.5) are used to kill gram negative bacteria, then bactericidal activity against gram negative bacteria is improved, but pharmaceutical agent stability may be compromised
Solution Approach 1:
The patent applies local quality by creating different pH conditions for different types of bacteria within the same buffer system. The extreme pH provides bactericidal activity specifically localized to gram-negative bacteria while being bacteriostatic to gram-positive bacteria, allowing selective elimination without compromising overall pharmaceutical stability
Solution Approach 2:
The patent uses partial action by applying extreme pH conditions that are sufficient to kill gram-negative bacteria but controlled enough to avoid excessive damage to the pharmaceutical agent. The low buffer capacity ensures the pH remains in the effective range long enough to be bactericidal without becoming excessively extreme
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 buffer system effectively reduces the occurrence of bloodstream infections by maintaining bactericidal activity against gram-negative bacteria and bacteriostatic activity against gram-positive bacteria and fungi, reducing morbidity and mortality rates associated with these infections.
Implementation Method 1
a buffer having a pH of greater than about 10 or less than about 4.5... selectively killing gram negative bacteria and inhibiting the growth of gram positive bacteria
Implementation Method 2
comprising glycine and sodium hydroxide or sorbic/citric acid, is used to selectively kill gram-negative bacteria
Data Source
AI summary
Buffer solutions for pharmaceutical preparations that have bactericidal activity preferentially against gram negative bacteria are provided. The buffers have a pH of greater than about 10 or less than about 4.5 with low buffer capacity. Methods of their use in reducing the occurrence of blood stream infections in a mammal is also provided.