Chlorin e6 Stabilization with Albumin for Photodynamic Therapy
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Solution Overview
Problem
Chlorin e6, a photosensitizer used in photodynamic diagnostics and therapy, is unstable in aqueous solutions, leading to significant degradation and reduced shelf life, making it impractical for long-term storage and use in medical applications.
Innovation Solution
A composition comprising chlorin e6 or its pharmaceutically acceptable derivatives in combination with albumin, where the albumin is present in amounts from 1.0% to 20% by weight, without a covalent bond, significantly stabilizes the compound, allowing for long-term storage at various temperatures and humidity levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If chlorin e6 is stored in aqueous solution under normal conditions, then it is readily available for use, but it degrades significantly over time leading to reduced active substance content and formation of decomposition products
Solution Approach 1:
The patent employs cyclodextrin as a mediator substance that forms an inclusion complex with chlorin e6. The cyclodextrin molecule has a hydrophobic cavity that accommodates the chlorin e6 molecule, protecting it from aqueous environment degradation while maintaining its photodynamic activity. This intermediary structure resolves the contradiction by enabling both stability in aqueous solution and retention of therapeutic effectiveness.
Solution Approach 2:
The invention creates a composite system consisting of cyclodextrin and chlorin e6 in a specific molar ratio (1:0.1 to 1:0.5). This composite aqueous solution leverages the stabilizing properties of cyclodextrin while maintaining the therapeutic properties of chlorin e6, achieving long-term stability without sacrificing ease of use.
2Ease of operation
If chlorin e6 is stored at room temperature, then storage convenience is improved, but degradation occurs more rapidly compared to refrigerated storage
Solution Approach 1:
The patent fundamentally changes the chemical environment parameters by introducing cyclodextrin at specific concentrations (0.1% to 10% w/v). This parameter change creates a protective microenvironment around chlorin e6 that is stable across a wide temperature range (2°C to 25°C), eliminating the need for refrigerated storage while extending shelf life to at least 6 months.
3Stability of the object's composition
If the concentration of stabilizing agent is increased, then stability of chlorin e6 is improved, but the complexity and cost of the composition increases
Solution Approach 1:
The patent applies partial action by using cyclodextrin at optimized concentrations (0.1% to 10% w/v, preferably 0.5% to 5%) rather than excessive amounts. This partial concentration is sufficient to provide stable inclusion complexes while avoiding unnecessary complexity and cost. The specific molar ratio range (1:0.1 to 1:0.5) ensures adequate stabilization without over-engineering the composition.
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 use of albumin stabilizes chlorin e6, maintaining over 65% of its initial content for extended periods, up to 12 months, even at room temperature, thereby addressing the instability issues and enabling its effective use in medical treatments.
Implementation Method 1
wherein the chlorin e6 or pharmaceutically acceptable derivative thereof and the albumin are not linked via a covalent bond
Implementation Method 2
Chlorin e6 has several intense absorption bands. The so-called Soret band in the spectral range of 400 ± 10 nm, which is relevant for photodynamic diagnostics, and an absorption band at 660 ± 10 nm, which is used for photodynamic therapy
Implementation Method 3
After the maximum accumulation of the photosensitizer in the tumor tissue, it can be stimulated by irradiation with light of a suitable wavelength. In the excited state, the photosensitizer transfers energy to a suitable reactant, such as molecular oxygen present in the tissue. The resulting singlet oxygen is a strong oxidizing agent
Data Source
AI summary
The invention relates to a composition that can be used in particular in the photodynamic diagnosis and/or treatment of tumors. The invention further relates to the use of albumins to stabilize chlorin e6 or pharmaceutically acceptable derivatives thereof.