Chlorin e4 analogues for photodynamic therapy
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Solution Overview
Problem
There is a need for chlorin e4 analogues and their pharmaceutically acceptable salts that exhibit high singlet oxygen quantum yield, strong photosensitizing ability, high fluorescence quantum yield, higher phototoxicity, lower dark toxicity, good stability, good solubility, and ease of purification, particularly in organic and aqueous media.
Innovation Solution
The development of chlorin e4 analogues and their pharmaceutically acceptable salts, specifically compounds of formula (I) or complexes of formula (II), which include various substituents and functional groups to enhance their photodynamic therapy and diagnostic capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chlorin e4 analogues are designed to enhance photosensitizing ability and singlet oxygen quantum yield, then photodynamic activity is improved, but molecular complexity increases making purification more difficult
Solution Approach 1:
The patent systematically varies substituents at specific positions (R1, R2, R3, R4, R5, R6, R7, R8) of the chlorin e4 core structure to optimize photodynamic properties. By changing parameters like substituent type, position, and configuration, the invention achieves enhanced singlet oxygen quantum yield and photosensitizing ability while maintaining manageable molecular complexity through controlled structural modification
Solution Approach 2:
The invention creates composite molecular structures by combining the chlorin e4 core with various substituent groups (alkyl, alkoxy, halo, nitro, amino groups, and fused ring systems). These composite structures achieve superior photodynamic activity by integrating multiple functional groups that work synergistically while the modular design facilitates systematic optimization and purification
2Reliability
If compounds are designed for high fluorescence quantum yield and strong photosensitizing ability, then diagnostic and therapeutic performance is improved, but solubility in organic and aqueous media may be compromised
Solution Approach 1:
The patent introduces different substituent groups at specific positions of the chlorin e4 molecule to create local variations in polarity and solubility characteristics. For example, hydrophilic groups (carboxylic acid, hydroxyl, amino) are placed at certain positions while hydrophobic groups (alkyl, aryl) are placed at others, creating molecules with balanced solubility in both organic and aqueous media while maintaining high fluorescence quantum yield
Solution Approach 2:
The invention systematically modifies molecular parameters including substituent type, chain length, and functional group configuration to optimize the balance between fluorescence quantum yield and solubility. By adjusting these parameters, the patent achieves compounds with both high diagnostic performance and appropriate solubility characteristics for different application scenarios
3Reliability
If phototoxicity is increased for better therapeutic effect, then treatment efficacy is improved, but dark toxicity may also increase causing harmful side effects
Solution Approach 1:
The patent designs compounds where the toxicological profile is dynamically controlled by light activation. The molecular structure is optimized to remain relatively inert in the dark (low dark toxicity) but becomes highly active upon light exposure (high phototoxicity). This dynamic behavior is achieved through careful selection of substituents that stabilize the ground state while facilitating photoexcitation and singlet oxygen generation
Solution Approach 2:
The invention adjusts molecular parameters such as substituent electron-donating/withdrawing capabilities, steric hindrance, and HOMO-LUMO energy gaps to fine-tune the balance between phototoxicity and dark toxicity. By optimizing these parameters, the patent achieves compounds with high therapeutic index where phototoxicity is maximized for treatment efficacy while dark toxicity is minimized to reduce side effects
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
These chlorin e4 analogues demonstrate improved photodynamic activity, stability, and solubility, making them promising candidates for photodynamic therapy, cytoluminescent therapy, and photodynamic diagnosis, while minimizing dark toxicity.
Implementation Method 1
Porphyrins and their analogues are known photosensitive chemical compounds, which can absorb light photons and emit them at higher wavelengths
Implementation Method 2
Chlorin e4 has been shown to display good photosensitive activity... There is a need for compounds that have a high singlet oxygen quantum yield and for compounds that have a strong photosensitizing ability
Data Source
AI summary
The present invention relates to chlorin e4 analogues and their pharmaceutically acceptable salts, and compositions comprising chlorin e4 analogues and their pharmaceutically acceptable salts. Chlorin e4 analogues and pharmaceutically acceptable salts thereof are suitable for use in photodynamic therapy, cytoluminescent therapy and photodynamic diagnosis, for example, for treating or C detecting a tumour, or for antiviral treatment. The present invention also relates to the use of chlorin e4 analogues and pharmaceutically acceptable salts thereof in the manufacture of a phototherapeutic or photodiagnostic agent, and to a method of photodynamic therapy, cytoluminescent therapy or photodynamic diagnosis, for example, for treating or detecting a tumour, or for antiviral treatment.