Bismuth Chelated Polymer Particles for X-Ray Embolization

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Solution Overview

Problem

Current imageable particles used in therapeutic embolization procedures, such as transarterial chemoembolization (TACE), face challenges in visualization during and after treatment due to radiopacity derived from iodinated species, leading to procedural variability and difficulty in distinguishing between embolic materials and iodine-based contrast agents.

Innovation Solution

Development of X-ray imageable polymer particles containing bismuth as a radiopacifying agent, which are designed to be visualized using X-ray technologies like multispectral CT or photon counting CT, and are differentiated from iodine-based contrast agents, with bismuth being chelated to ensure optimal radiodensity and compressibility for effective embolization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If iodinated species are used to provide radiopacity in embolic particles, then X-ray visualization is achieved, but the particles become more dense and less compressible, limiting their administration through microcatheters and causing sedimentation

Engineering Contradiction:
ImproveX-ray visualization capabilityVSAvoidcompressibility and administrability
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent changes the radiopacifying agent from iodine to bismuth, altering the chemical composition parameter. Bismuth provides comparable radiopacity but with different physical properties - specifically lower density and higher compressibility, allowing particles to be administered through microcatheters without clumping while maintaining X-ray visibility

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite embolic particles combining bismuth subcarbonate with polymer materials (such as polyvinyl alcohol or gelatin). This composite structure achieves the desired balance between radiopacity (from bismuth) and mechanical properties (from polymer matrix), enabling both visualization and proper flow characteristics for microcatheter administration

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If iodinated particles are used for embolization, then radiopacity is achieved, but it becomes difficult to distinguish between the iodinated particles and soluble iodinated contrast agents in X-ray imaging

Engineering Contradiction:
ImproveradiopacityVSAvoiddifferentiation capability
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent changes the elemental composition from iodine to bismuth, which has different X-ray attenuation characteristics. This allows differentiation from iodine-based contrast agents through dual-energy CT or photon-counting CT imaging, as bismuth and iodine have distinct atomic numbers and energy absorption profiles

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs advanced imaging technologies (dual-energy CT or photon-counting CT) as intermediaries to distinguish bismuth particles from iodine contrast agents. These imaging systems can selectively identify and differentiate between different contrast materials based on their unique energy interaction signatures, providing clear visualization without confusion

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If higher density radiopacifying agents are used to improve X-ray density, then imaging capability is enhanced, but particle compressibility decreases, limiting their passage through microcatheters

Engineering Contradiction:
ImproveX-ray densityVSAvoidcompressibility
Core Design Contradiction:
Measurement precisionVSStrength

Solution Approach 1:

The patent selects bismuth subcarbonate as the radiopacifying agent, which provides sufficient X-ray density (bismuth has high atomic number 83) but with lower physical density compared to iodine compounds. This parameter optimization allows the particles to maintain both imaging capability and deformability for microcatheter passage

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent formulates composite particles where bismuth subcarbonate is dispersed within a compressible polymer matrix (such as gelatin or polyvinyl alcohol). The polymer matrix provides the necessary compressibility and flexibility, while the bismuth subcarbonate provides radiopacity, creating a composite material that satisfies both requirements simultaneously

Inventive Principle:
Principle #40Composite materials

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 bismuth-containing polymer particles provide clear X-ray imaging, reducing procedural variability and allowing for precise localization of embolic materials, enhancing the safety and efficacy of TACE procedures by distinguishing them from iodine-based contrast agents.

Implementation Method 1

An X-ray imageable polymer, which may be in the form of particles (such as in the present invention) such as microspheres, comprises bismuth as an imageable agent

Methodology Applied
Scientific EffectX-ray absorption: Absorption (EM radiation)

Implementation Method 2

bismuth being chelated to ensure optimal radiodensity and compressibility for effective embolization

Methodology Applied
Scientific EffectChelation: Chemical Bonding

Data Source

PatentEP3541368B1Imageable particles, methods of making and methods of use thereof
Publication Date: 2023.07.12 BIOCOMPATIBLES UK LTD
  • EP3541368B1 patent drawingFigure 1~4
  • EP3541368B1 patent drawingFigure 5~6
  • EP3541368B1 patent drawingFigure 7~8

AI summary

Described herein are X-ray imageable polymers such as polymeric particles comprising bismuth as a radiopacifying agent, methods of making the polymers, and methods of using the polymers. The imageable particles may comprise a covalently bound compound which chelates the bismuth, for example, through a combination of nitrogen and oxygen atoms.