Chlorin e4 Sodium Photosensitizer Singlet Oxygen Yield

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Solution Overview

Problem

Current photosensitizers for photodynamic therapy lack high singlet oxygen quantum yield and strong photosensitizing ability, especially in organic and aqueous media, necessitating the development of compounds with enhanced fluorescence and photophysical properties.

Innovation Solution

Chlorin e4 sodium is synthesized, preferably in a substantially enantiomerically pure form, through reaction with a sodium compound like sodium hydroxide, in the presence of a base such as thiamine pyrophosphate, and purified using methods like filtration and chromatography, to create a pharmaceutical composition suitable for photodynamic therapy and diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional photosensitizers are used, then photodynamic therapy can be performed, but the singlet oxygen quantum yield and photosensitizing ability are insufficient

Engineering Contradiction:
Improvephotosensitizing abilityVSAvoidsinglet oxygen quantum yield
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the chemical structure of chlorin e4 by converting it to its sodium salt form, which fundamentally changes its photophysical parameters. This parameter change results in enhanced singlet oxygen quantum yield and improved photosensitizing ability in both organic and aqueous media, directly resolving the contradiction between reliability and productivity of photosensitizers

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite pharmaceutical composition containing chlorin e4 sodium combined with appropriate excipients and carriers. This composite formulation optimizes the delivery and performance of the photosensitizer, enhancing both its reliability in producing singlet oxygen and its productivity in therapeutic applications

Inventive Principle:
Principle #40Composite materials

2Reliability

If enantiomerically pure chlorin e4 sodium is synthesized, then therapeutic efficacy is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidsynthesis complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs chiral resolution or asymmetric synthesis methods during the preliminary stages of chlorin e4 sodium production to obtain enantiomerically pure material. By performing the chirality selection early in the synthesis pathway, the method ensures high therapeutic efficacy while managing manufacturing complexity through proactive rather than reactive purification

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The use of chiral resolving agents or asymmetric catalysts as intermediaries during synthesis enables the separation or formation of enantiomerically pure chlorin e4 sodium. These intermediary substances facilitate the获得 of high optical purity without requiring excessively complex multi-step purification processes, thus balancing therapeutic efficacy with manufacturability

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Chlorin e4 sodium exhibits strong fluorescence and photosensitizing ability in both organic solvents and aqueous media, with high singlet oxygen quantum yield, effectively treating and detecting tumors with minimal side effects.

Implementation Method 1

Porphyrins and their derivatives are known photosensitive chemical compounds, which can absorb light photons and emit them at higher wavelengths. During light activation, a molecule goes from the ground state (S 0 ) to a singlet excited state (S 1 ), (S 0 →S 1 transition), and then falls back down to the ground state (S 0 ), (S 1 →S 0 transition), emitting light at higher wavelengths in the form of fluorescence.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The triplet state (T 1 ) cannot be efficiently populated by direct excitation. However, intersystem crossing S 1 →T 1 occurs isoenergetically followed by deactivation to T 1. The S 1 →T 1 change is formally spin-forbidden, but it is a downhill process and in some molecules intersystem crossing occurs so efficiently that fluorescence is quenched. Such compounds are useful for generating excited triplets by excitation transfer (a phenomenon known as sensitization) in molecules where the intersystem crossing is minimal.

Methodology Applied
Scientific EffectIntersystem crossing:

Implementation Method 3

At the triplet state (T 1 ) molecules become very unstable and can react with molecular oxygen ( 3O 2 ) to generate singlet oxygen ( 1O 2 ).

Methodology Applied
Scientific EffectPhoto-oxidation: Photo-oxidation

Data Source

PatentEP2931728B1Chlorin derivative useful in photodynamic therapy and diagnosis
Publication Date: 2020.02.19 RMW CHO GROUP
  • EP2931728B1 patent drawingFigure 1
  • EP2931728B1 patent drawingFigure 2~3
  • EP2931728B1 patent drawingFigure 4

AI summary

The present invention relates to chlorin e4 sodium and a process for its preparation. Chlorin e4 sodium is suitable for use in photodynamic therapy, cytoluminescent therapy and photodynamic diagnosis, for example for treating or detecting a tumour. The present invention also relates to a pharmaceutical composition comprising chlorin e4 sodium, to the use of chlorin e4 sodium 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.