Hypericin Formulation for Selective Tumor Accumulation

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Solution Overview

Problem

Current photodynamic therapy (PDT) formulations of hypericin face challenges in achieving clinical stability and selective tumor accumulation, requiring high light intensities for effective tumor cell killing, which can lead to increased local side effects.

Innovation Solution

A formulation of hypericin bound to a polymeric complexing agent, such as polyethylene glycol or poly-N-vinylamide, in the form of an alkali metal salt, specifically sodium or potassium salt, which enhances stability and selective accumulation in tumor cells, allowing for reduced light intensity treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high light intensity is used for PDT treatment, then tumor cell killing effectiveness is improved, but local side effects increase

Engineering Contradiction:
Improvetumor cell killing effectivenessVSAvoidlocal side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by modifying the photosensitizer properties to achieve selective accumulation in tumor cells. The photosensitizer is designed to concentrate specifically in malignant tissue, allowing effective treatment with lower light intensities while minimizing exposure to healthy surrounding tissues, thus reducing local side effects while maintaining tumor cell killing effectiveness.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the chemical parameters of the photosensitizer by developing a water-soluble formulation with improved pharmacokinetic properties. This includes modifying the molecular structure to enhance tumor selectivity and accumulation, which allows the use of reduced light intensity (5-25 mW/cm²) while achieving the same therapeutic effect, thereby resolving the contradiction between effectiveness and side effects.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If hypericin is used in water-soluble form, then clinical applicability is improved, but stability and selective accumulation are reduced

Engineering Contradiction:
Improveclinical applicabilityVSAvoidstability and selective accumulation
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs composite materials by creating a photosensitizer formulation that combines hydrophobic hypericin with hydrophilic carriers or modifying agents. This composite approach maintains water solubility for clinical administration while preserving or enhancing tumor selectivity and stability through the synergistic properties of the composite system.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent applies parameter changes by systematically optimizing the chemical structure and formulation parameters of hypericin. This includes adjusting solubility, molecular weight, and chemical composition to achieve the optimal balance between water solubility (for clinical use) and tumor selectivity/stability, transforming the original compound into a clinically applicable form without sacrificing therapeutic performance.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If reduced light intensity is used, then local side effects are reduced, but tumor cell killing effectiveness decreases

Engineering Contradiction:
Improvelocal side effectsVSAvoidtumor cell killing effectiveness
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies local quality by enhancing the photosensitizer's selective accumulation in tumor cells, which compensates for the reduced light intensity. The concentrated photosensitizer in the tumor tissue generates sufficient reactive oxygen species even with lower light doses, maintaining killing effectiveness while reducing side effects in surrounding healthy tissues.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the photosensitizer parameters to achieve higher quantum efficiency and tumor selectivity, which allows the therapeutic effect to be maintained at lower light intensities. The optimized photosensitizer properties enable effective PDT treatment with reduced light dosage, simultaneously achieving lower side effects and maintained effectiveness.

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 formulation achieves up to 98% tumor cell killing with significantly lower light intensities, ensuring effective PDT with reduced side effects and improved stability for clinical use.

Implementation Method 1

hypericin bound to a polymeric complexing agent, namely a polyethylene glycol or a poly-N-vinylamide

Methodology Applied
Scientific EffectComplexation:

Implementation Method 2

the photosensitizer accumulates in the malignant tissue

Methodology Applied
Scientific EffectSelective accumulation:

Implementation Method 3

The photosensitizer can be excited using light of a suitable wavelength. In the excited state, energy is transferred to a reaction partner, such as molecular oxygen. This generates reactive oxygen molecules

Methodology Applied
Scientific EffectPhotoexcitation:

Implementation Method 4

energy is transferred to a reaction partner, such as molecular oxygen. This generates reactive oxygen molecules, which in turn damage cellular structures

Methodology Applied
Scientific EffectPhotooxidation: Photo-oxidation

Data Source

PatentEP3237010B1Formulation of hypericin for photodynamic therapy
Publication Date: 2019.08.14 SANOCHEMIA PHARMAZEUTIKA AG
  • EP3237010B1 patent drawingFigure 1~2

AI summary

A formulation which can be used as a photosensitizer in the therapy of cancer, for example bladder cancer, contains polyvinylpyrrolidone-bound or polyvinylpyrrolidone-complexed hypericin sodium salt.