Trichloroacetic Acid Salts of 5-ALA for Reduced Skin Irritation

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Solution Overview

Problem

The hydrochloride salts of 5-aminolevulinic acid (5-ALA) and its esters exhibit skin irritation, inflammation, hygroscopicity, and inadequate skin penetration, limiting their effectiveness in photodynamic therapy (PDT).

Innovation Solution

The development of trichloroacetic acid (TCA) salts of 5-ALA and its esters, which are less irritating, less hygroscopic, and exhibit enhanced skin penetration, offering improved physicochemical properties and synergistic therapeutic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hydrochloride salts of 5-ALA and its esters are used as photosensitizing agents, then they can be provided in stable pharmaceutical formulations, but they exhibit skin irritation, inflammation, and hygroscopicity that limit therapeutic effectiveness

Engineering Contradiction:
Improvestability of pharmaceutical formulationVSAvoidskin irritation and inflammation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameter of the salt form from hydrochloride to trichloroacetate. This parameter change fundamentally alters the properties of the photosensitizing agent, reducing skin irritation and hygroscopicity while maintaining pharmaceutical stability and therapeutic effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The trichloroacetate ion acts as an intermediary that modifies the interaction between 5-ALA and biological tissues. By forming a salt with different chemical properties, it mediates reduced harmful effects on skin while preserving the photosensitizing function.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If hydrochloride salts of 5-ALA and its esters are used, then they are available for clinical application, but they exhibit inadequate skin penetration that limits PDT effectiveness

Engineering Contradiction:
Improveavailability for clinical applicationVSAvoidskin penetration depth
Core Design Contradiction:
Ease of manufactureVSLength of moving object

Solution Approach 1:

Changing the salt form from hydrochloride to trichloroacetate modifies the physicochemical parameters including solubility, permeability, and skin penetration characteristics. This enables deeper and more effective penetration into skin tissues while maintaining clinical applicability.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If hydrochloride salts of 5-ALA and its esters are used, then they can be formulated for topical application, but their hygroscopicity causes degradation during storage

Engineering Contradiction:
Improvetopical application formulationVSAvoidstability during storage
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the hygroscopicity parameter by switching from hydrochloride to trichloroacetate salt form. This reduces water absorption during storage, preventing degradation and extending shelf life while maintaining ease of topical formulation and application.

Inventive Principle:
Principle #35Parameter changes

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 TCA salts of 5-ALA and its esters demonstrate reduced skin irritation, improved stability, and enhanced skin penetration, leading to more effective PDT with dual action in treating acne and other dermatological conditions.

Implementation Method 1

Upon exposure to visible light, the photosensitizer is activated to high energy states and further reacts with oxygen or transfer its energy to oxygen molecules to create reactive oxygen species (ROS)

Methodology Applied
Scientific EffectPhotosensitization: Photo-oxidation

Implementation Method 2

The activated photosensitizer can also return to a lower energy level partly by emitting red fluorescence, which can be used for diagnostic purposes

Methodology Applied
Scientific EffectFluorescence emission: Fluorescence

Data Source

PatentEP3408254B1Salts of 5-aminolevulinic acid and derivatives
Publication Date: 2020.11.04 ZHAO MING

AI summary

The present disclosure provides new salts of 5-aminolevulinic acid (5-ALA) and new salts of 5-ALA esters, their preparation, formulation and use as photosensitizing agents in photodynamic therapy, diagnosis and cosmetic cares.