Water-Soluble TPCS 2a Salt for Parenteral Photochemical Internalization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Amphiphilic photosensitizing agents used in photochemical internalization (PCI) exhibit poor aqueous solubility, leading to precipitation and severe side effects when administered parenterally, making them unsuitable for clinical use due to low solubility in aqueous solutions.
Innovation Solution
Development of a water-soluble salt of meso-tetraphenyl chorin disulphonate (TPCS 2a) as a pharmaceutically acceptable amphiphilic photosensitizing agent, specifically the bis(monoethanolamine) salt, which is highly soluble and forms a stable solution for parenteral administration, reducing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If amphiphilic photosensitizing agents are used for photochemical internalization, then the photochemical internalization efficiency is improved, but the aqueous solubility deteriorates leading to precipitation and severe side effects
Solution Approach 1:
The patent changes the chemical form of the photosensitizing agent from neutral/amphiphilic to anionic salt form. This parameter change in charge state fundamentally alters the solubility characteristics, enabling water-soluble formulations while maintaining the amphiphilic structure necessary for PCI activity. The salt formation transforms the solubility parameter without compromising the functional properties.
Solution Approach 2:
The patent introduces salt-forming cations (such as sodium, potassium, or ammonium ions) as intermediary substances that mediate between the amphiphilic photosensitizing agent and the aqueous environment. These cations form ionic bonds with the photosensitizing agent, creating water-soluble salt complexes that bridge the gap between hydrophobic PCI activity and hydrophilic solubility requirements.
2Adaptability or versatility
If amphiphilic photosensitizing agents are administered parenterally, then the treatment can be given systemically, but precipitation occurs causing severe side effects
Solution Approach 1:
The patent modifies the physical-chemical parameters of the photosensitizing agent by converting it to an ionic salt form. This changes the solubility parameter from poor aqueous solubility to high water solubility, enabling safe parenteral administration without precipitation-related toxicity while maintaining systemic deliverability.
Solution Approach 2:
The patent converts the potentially harmful precipitation issue into a beneficial soluble formulation. By forming water-soluble salts, the agent that would normally precipitate and cause harm is transformed into a formulation that remains dissolved, converting the precipitation problem into a solution for safe parenteral administration.
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 water-soluble TPCS 2a salt enhances the solubility and stability of the photosensitizer, allowing for effective parenteral administration without severe side effects, enabling efficient photochemical internalization of drug molecules into cells.
Implementation Method 1
Exposure of the cells to light of a suitable wavelength activates the photosensitizing agent
Implementation Method 2
Both mechanisms go through a pathway involving singlet oxygen species. Singlet oxygen is a highly reactive form of oxygen that can oxidize various biomolecules, including molecules in the cellular membranes.
Data Source
AI summary
The invention relates to pharmaceutically acceptable salts of amphiphilic photosensitizing agents which have a water solubility of at least 0.5 mg/ml and to their use in methods of photochemical internalization. Such salts may be formed from a pharmaceutically acceptable base, for example an organic amine such as an amino alcohol, or from a pharmaceutically acceptable acid, for example a sulphonic acid or a sulphonic acid derivative. Due to their increased water solubility, such salts are particularly suitable for use in the preparation of parenteral pharmaceutical preparations, e.g. for use as solutions for injection or infusion.