Imageable polymers, methods of making and methods of use thereof
Inventors
Negussie, Ayele H. • Wood, Bradford Johns
Assignees
Usa REPRESENTED BY SECRETARY Dhhs AS • US Department of Health and Human Services
Publication Number
US-11382990-B2
Publication Date
2022-07-12
Expiration Date
2037-10-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
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.
Core Innovation
The invention relates to X-ray imageable polymers, particularly polymeric particles, comprising bismuth as a radiopacifying agent, methods of making these polymers, and methods of their use. The imageable particles comprise a covalently bound compound that chelates bismuth through nitrogen and oxygen atoms, allowing the polymer to be visualized within the body by X-ray imaging techniques such as CT or micro-CT. The bismuth is coordinated to a complexing molecule covalently linked to the polymer, providing high X-ray opacity while maintaining physical properties of embolic particles such as compressibility and size appropriate for vascular delivery.
The background identifies a significant problem in therapeutic transarterial embolization (TACE) treatment modalities, notably the inability to visualize embolic materials during and post-treatment due to limitations of existing iodinated radiopaque particles. These iodinated particles sediment quickly, are less compressible, and are difficult to distinguish from commonly used iodinated contrast agents. This leads to procedural variability and challenges in precisely determining injection locations and treatment endpoints.
The invention addresses this by providing novel imageable particles incorporating bismuth as an alternative radiopacifying agent. Bismuth-containing polymers offer improved radiopacity enabling differentiation from iodine-based contrast agents, with particle properties like density and compressibility comparable to conventional embolic materials. The polymers use chelating molecules covalently bound to the polymer to coordinate bismuth effectively, providing stability and high radiodensity suitable for imaging applications.
Claims Coverage
The patent contains multiple independent claims covering imageable bismuth particles, their composition, methods for their manufacture, and their use in imaging and treatment methods.
Imageable bismuth particle composition
A hydrophilic polymer particle of 40 to 700 μm diameter comprising a covalently bound compound coordinating bismuth via specific structural formulas involving complexing molecules, linking groups, and functional groups.
Hydrophilic polymer characteristics
The polymer particle is spherical and comprises polymers such as polyvinyl alcohol, polyvinyl acetal, carboxymethylcellulose, and others suitable for hydrophilic, water-swellable, but water-insoluble particles.
Chemistry of covalent bonding and linker groups
The covalently bound compound includes complexing molecules connected via functional groups (A) and linking groups (L) with defined chemical structures and valencies, ensuring effective bismuth chelation and polymer attachment.
Reversibly bound active agent inclusion
The particle may include a reversibly bound active agent, such as a chemotherapeutic agent, allowing for drug delivery in addition to embolization and imaging.
Methods of making imageable bismuth particles
Methods include reacting hydrophilic polymer precursor particles with cyclen or azanyl compounds or their bismuth complexes under conditions permitting covalent bonding and chelation, producing stable imageable particles.
Methods of imaging bismuth particles in subjects
Administering the imageable bismuth particles intraarterially, using catheters and optionally with contrast agents, with imaging performed via dual energy CT or photon counting CT to visualize particle location in vessels.
Methods of treating tumors
Intraarterially administering imageable bismuth particles containing reversibly bound chemotherapeutic agents to arteries supplying tumors such as hepatocellular carcinoma or tumors in specified organs, followed by imaging and drug release.
The claims cover imageable bismuth-containing polymeric particles with defined chemical compositions, methods of their preparation using covalent bonding of bismuth-chelating compounds to hydrophilic polymers, and their novel use in imaging and treating tumors by intraarterial administration with imaging techniques that differentiate bismuth particles from iodine contrast agents.
Stated Advantages
The imageable bismuth particles can be visualized and distinguished from iodine-containing contrast agents during X-ray imaging, reducing procedural variability.
Particles have density and compressibility comparable to conventional embolic particles, facilitating ease of administration through microcatheters without clumping.
The use of bismuth as a radiopacifying agent provides high radiodensity, enabling imaging by dual-energy or photon counting CT with enhanced contrast.
The covalent chelation of bismuth ensures stability of the radiopaque particles, retaining imaging properties even after sterilization processes like autoclaving.
Documented Applications
Loco-regional therapeutic embolization in treatment of hypervascular tumors, for example using transarterial chemoembolization (TACE) to treat hepatocellular carcinoma and other tumors.
Intravascular imaging methods, including intraarterial administration of imageable bismuth particles with subsequent imaging by X-ray modalities such as dual-energy or photon counting CT.
Drug delivery via embolic particles that reversibly bind active pharmaceutical agents, releasing them into target blood vessels during embolization therapy.
Treatment of benign tumors or hyperplasias such as benign prostate hyperplasia or uterine fibroids, and procedures like gastric artery embolization for weight loss.
Interested in licensing this patent?