Cationic Phthalocyanine Analogues for Gram-Negative Bacteria Inactivation
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Solution Overview
Problem
Current phthalocyanine-based photodynamic therapies are less effective against Gram negative bacteria due to lower photoinactivation rates compared to Gram positive bacteria and yeast, necessitating the development of novel compositions with enhanced photodynamic properties to improve bacterial inactivation efficiency while minimizing side effects.
Innovation Solution
The use of phthalocyanine analogues peripherally substituted with cationic groups or groups protonable at physiological pH, in combination with metal chelating agents like CDTA, DTPA, and EDTA, to enhance photoinactivation efficacy against Gram negative bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional phthalocyanine photosensitizers are used for photodynamic therapy, then photoinactivation of Gram positive bacteria is effective, but photoinactivation of Gram negative bacteria is significantly less effective (at least one order of magnitude lower)
Solution Approach 1:
The patent applies local quality by introducing cationic groups at specific peripheral positions of the phthalocyanine molecule. This modifies the local charge distribution to enable interaction with the negatively charged outer membrane of Gram negative bacteria, while maintaining the core photodynamic properties needed for Gram positive bacteria and yeast inactivation.
Solution Approach 2:
The patent changes the chemical parameter of the phthalocyanine molecule by adding cationic substituents (such as quaternary ammonium groups). This parameter change alters the electrostatic interaction properties, enabling the photosensitizer to overcome the permeability barrier of Gram negative bacteria and achieve effective photoinactivation across all three bacterial types.
2Reliability
If additional substances like Ca2+ salts or Tris-EDTA are used to alter membrane permeability for Gram negative bacteria, then photoinactivation efficacy improves, but treatment complexity and potential side effects increase
Solution Approach 1:
The patent merges the photosensitizer function and the membrane interaction function into a single molecular entity. The cationic phthalocyanine molecules combine light-activated singlet oxygen generation with electrostatic attraction to bacterial membranes, eliminating the need for separate permeability-altering agents and simplifying the treatment composition.
Solution Approach 2:
The cationic phthalocyanine molecules perform self-service by autonomously interacting with the negatively charged outer membrane of Gram negative bacteria through electrostatic attraction. This self-directed membrane interaction eliminates the need for external agents to facilitate permeability changes, reducing treatment complexity.
3Productivity
If higher concentrations of phthalocyanine photosensitizer are used to achieve complete sterilization of Gram negative bacteria, then bacterial inactivation efficiency improves, but toxicity to healthy tissues increases
Solution Approach 1:
The cationic groups are localized at the periphery of the phthalocyanine molecule, creating a dipole structure where the charged regions interact with bacterial membranes while the core photodynamic region remains intact. This spatial separation allows selective targeting of bacteria while maintaining controlled photodynamic activity, reducing off-target toxicity.
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
This combination achieves a synergistic effect, significantly increasing the photoinactivation efficiency of cationic phthalocyanine photosensitizers, allowing for complete sterilization of bacterial suspensions at lower concentrations and reduced light exposure, minimizing toxicity to healthy tissues.
Implementation Method 1
phthalocyanines are molecules able to produce singlet oxygen in good yields as a result of light irradiation and have therefore photoenhanced biocidal activity
Implementation Method 2
metal chelating agents having a specificity for the Ca2+ and Mg2+ ions, such as 1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA), diethylenetriamine-pentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA)
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising metal phthalocyanine analogues of formula (I) and metal chelating compounds having a good bioavailability and enhanced photoinactivation properties against Gram negative bacteria; and to their use for in vivolex vivo applications, such as blood and blood derivatives sterilization.