Phosphazene-Coated Hydrogel Microspheres for Embolization Imaging

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Solution Overview

Problem

Current small particles used in medical applications often cause tissue irritation, induce adverse immune reactions, and degrade rapidly within the mammalian body, leading to toxic compound release, while also settling or aggregating, making them difficult to visualize and deliver uniformly.

Innovation Solution

Development of microspheres with an acrylic-based hydrogel core and a poly[bis(trifluoroethoxy)]phosphazene coating, incorporating a color-coded dye for size identification and barium sulfate to prevent agglomeration, ensuring biocompatibility and stability, and using a cryoextraction method for preparation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If conventional materials are used to prepare particles, then particle formation is achieved, but the particles cause tissue irritation and induce adverse immune reactions

Engineering Contradiction:
Improvetissue irritation and immune reactionsVSAvoidbiocompatibility
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent uses a composite structure consisting of an acrylic-based hydrogel polymer core and a poly[bis(trifluoroethoxy)]phosphazene coating. This composite material combines the benefits of both materials: the hydrogel core provides biocompatibility and stability, while the phosphazene coating enhances imaging visibility and prevents aggregation, thereby resolving the contradiction between particle functionality and biocompatibility

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent applies different materials to different parts of the particle structure to achieve specific functions. The core uses acrylic-based hydrogel polymer for biocompatibility and structural integrity, while the surface coating uses poly[bis(trifluoroethoxy)]phosphazene for imaging enhancement and anti-aggregation properties. This local differentiation allows each material to optimize its specific function without compromising overall biocompatibility

Inventive Principle:
Principle #3Local quality

2Difficulty of detecting and measuring

If particles are made visible using contrast agents, then visualization is improved, but particles may aggregate or settle in solution

Engineering Contradiction:
Improvevisualization difficultyVSAvoidsuspension stability
Core Design Contradiction:
Difficulty of detecting and measuringVSStability of the object's composition

Solution Approach 1:

The patent combines multiple functions into a single coating layer: the poly[bis(trifluoroethoxy)]phosphazene coating simultaneously provides contrast agent incorporation capability for imaging visibility and surface properties that prevent particle aggregation and settling. This merging eliminates the need for separate stabilization additives and dispersing agents, maintaining suspension stability while achieving excellent visualization

Inventive Principle:
Principle #5Merging (Combining)

3Stability of the object's composition

If dispersing agents and thickening agents are added to achieve stable dispersion, then suspension stability is improved, but formulation complexity increases

Engineering Contradiction:
Improvedispersion stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the need for multiple separate formulation additives (surfactants, thickening agents, density additives) by incorporating their functions directly into the particle structure itself. The phosphazene coating provides inherent anti-aggregation and suspension stability properties, allowing the formulation to achieve stable dispersion without complex additive mixtures

Inventive Principle:
Principle #2Taking out (Extraction)

4Object-affected harmful factors

If clear transparent polymeric acrylate hydrogel beads are used, then biocompatibility is maintained, but visualization in suspension becomes difficult

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidvisualization difficulty
Core Design Contradiction:
Object-affected harmful factorsVSDifficulty of detecting and measuring

Solution Approach 1:

The patent incorporates contrast agents into the phosphazene coating to provide radiopacity and enhanced imaging visibility. This allows the particles to maintain their clear transparent hydrogel core for biocompatibility while the coating layer provides the necessary contrast for visualization during clinical procedures through X-ray and other imaging modalities

Inventive Principle:
Principle #32Color 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 microspheres remain stable and non-toxic, preventing immune reactions, maintaining visibility in suspension, and allowing for precise delivery and visualization, enhancing embolization therapy by assessing tumor size changes through clinical imaging.

Implementation Method 1

the coating comprises poly[bis(trifluoroethoxy)]phosphazene... Other attempts to increase visualization of microparticles include the use of gold... which provides a magenta color to acrylate microparticles

Methodology Applied
Scientific EffectRadiopacity: X-Ray

Implementation Method 2

Barium sulfate also is known for improving fluidization, and is often used as an inorganic filler to impart anti-stick behavior to moist, aggregated particles

Methodology Applied
Scientific EffectFluidization: Fluidisation

Implementation Method 3

the core comprises an acrylic-based hydrogel polymer... are biocompatible, are easy to visualize in suspension while in use

Methodology Applied
Scientific EffectHydrogel: Hydrogel

Implementation Method 4

using a cryoextraction method for preparation

Methodology Applied
Scientific EffectCryoextraction: Freezing

Data Source

PatentEP2214718B1Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
Publication Date: 2017.04.12 BOSTON SCI LTD
  • EP2214718B1 patent drawingFigure 1~1c
  • EP2214718B1 patent drawingFigure 2
  • EP2214718B1 patent drawingFigure 3A~3B

AI summary

Particles are provided for use in therapeutic and/or diagnostic procedures. The particles include poly[bis(trifluoroethoxy) phosphazene] and/or a derivatives thereof which may be present throughout the particles or within an outer coating of the particles. The particles can also include a core having a hydrogel formed from an acrylic-based polymer. Such particles may be provided to a user in specific selected sizes to allow for selective embolization of certain sized blood vessels or localized treatment with an active component agent in specific clinical uses. Microspheres of the present invention may further be provided with physical and/or chemical enhancements within the particles' cores to enhance visualization of the embolized tissue using a variety of medical imaging modalities, including conventional radiography, fluoroscopy, tomography, computerized tomography, ultrasound, scintillation, magnetic resonance, or other imaging technologies.