Embolic compositions and methods
Inventors
Groom, Jeffrey • WILTSEY, Craig • Pham, Quynh • MANSUKHANI, Nikhita • Guertin, Courtney • Core, Lee • Sharma, Upma
Assignees
Publication Number
US-12285537-B2
Publication Date
2025-04-29
Expiration Date
2041-06-09
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Abstract
The present disclosure pertains to crosslinkable compositions and systems as well as methods for forming crosslinked compositions in situ, including the use of the same for embolizing vasculature including the neurovasculature within a patient, among many other uses.
Core Innovation
The invention relates to crosslinkable compositions and systems, as well as methods for forming crosslinked compositions in situ, particularly for use in embolizing vasculature, including the neurovasculature of a patient. The compositions are based on mixtures of specific fluid and dry components that, when combined, form a crosslinkable polymer system capable of curing and solidifying within targeted body sites. The inventive system includes formulations where a first fluid composition containing a crosslinkable polymer and an imaging agent is mixed with a second fluid composition containing a crosslinker (such as a hydride material) and, optionally, a second imaging agent, together with dry silica fillers.
The problem addressed by the invention stems from the need for biomedical materials that can be delivered to closed cavities or difficult-to-access anatomical sites, especially within the vasculature, and can reliably fill, support, and occlude such spaces after delivery. Prior limitations include challenges in delivering in-situ-forming materials that provide controlled flow, deep vascular penetration, and robust occlusion, while allowing imaging compatibility and maintaining injectability through catheters. The invention seeks to overcome these challenges by providing shear-thinning, flow-responsive materials with customized physical properties for safe and effective vascular embolization.
The disclosed methodology includes the preparation of kits and compositions that utilize multiple phases—fluid and dry—to maintain or improve the dispersion of imaging and filler particles (such as bismuth trioxide and silica). These compositions are engineered to allow hand-injectable delivery through catheters, exhibit shear-thinning properties for deep anatomical penetration, respond to changing flow conditions in target vasculature, and cure into a solid form to achieve durable vessel occlusion. The systems allow component ratios, particle sizes, rheological properties, and catalytic cure behaviors to be finely controlled for clinical uses, especially in vascular embolization contexts.
Claims Coverage
The patent contains three independent claims, each focusing on methods for preparing and using crosslinkable compositions for vascular embolization involving specific polymers, fillers, and imaging agents.
Vascular embolization via in situ crosslinkable composition from fluid and dry phase mixing
This feature involves: - Providing a first fluid composition containing a crosslinkable polymer and a first imaging agent with a specified particle size (80 nm to 200 nm). - Providing a second fluid composition containing a crosslinker and, optionally, a second imaging agent (same particle size range). - Mixing both fluid compositions with a dry composition comprising at least a first silica filler, and optionally a second silica filler. - Ensuring the agents and fillers are dispersed in the crosslinkable composition. - Preparing for injection and injecting the composition into vasculature where it flows to and occludes the target vessel, followed by in situ crosslinking into a solid.
Vascular embolization using crosslinkable polysiloxane and hydride compositions with dispersed fillers and imaging agents
This inventive feature includes: - Providing a first fluid composition containing a polysiloxane with two or more unsaturated groups and a first imaging agent (particle size 80 nm to 200 nm). - Providing a second fluid composition containing a hydride material with two or more hydride groups and, optionally, a second imaging agent (same size range). - Mixing the fluid compositions with a dry composition that includes one or more fillers (same or different). - Achieving substantial even dispersion of the imaging agents and fillers in the final crosslinkable composition. - Preparing and injecting the composition into a vascular site to flow and occlude a target vessel before curing solid in situ.
Vascular embolization with bismuth trioxide-imparted radiopacity and crosslinkable fillers
This feature consists of: - Providing a first fluid composition containing a crosslinkable polymer and bismuth trioxide (average primary particle size 80 nm to 200 nm). - Providing a second fluid composition comprising a crosslinker, and optionally bismuth trioxide of the same particle size range. - Mixing these with a dry composition containing at least a first filler (optionally a second, same or different). - Dispersion of bismuth trioxide and fillers throughout the crosslinkable composition. - Preparing for and performing injection such that the composition flows into, occludes, and then crosslinks in a targeted vessel.
The patent claims center on methods for forming and delivering specific crosslinkable compositions from defined mixtures of fluids and dry components, utilizing particular polymers, crosslinkers, fillers, and imaging agents (notably bismuth trioxide), to achieve precise, flow-responsive, and in situ curing embolic occlusion within the vasculature.
Stated Advantages
The compositions can be delivered to closed cavities and difficult-to-access body sites, filling empty or blood-filled spaces and supporting surrounding tissues.
Shear-thinning properties allow for microcatheter injection and flow responsiveness, enabling deep distal penetration and controlled proximal delivery within the vasculature.
The material forms a solid cast for complete vessel occlusion without non-target embolization and shows good radiopacity for imaging.
Injection can be performed by hand, maintaining clinical simplicity while delivering precise embolization.
The compositions exhibit biocompatibility and minimal inflammation, vessel injury, necrosis, or hemorrhage, as shown in animal studies.
Material rheological properties and injection force can be tuned by component selection and preparation method, optimizing both injectability and structural behavior.
The formulations are compatible with terminal sterilization methods such as electron-beam irradiation.
Radiopaque agents such as bismuth trioxide facilitate imaging while minimizing risks associated with alternative agents (e.g., reduced risk of sparking and fire).
The compositions remain flowable until cure, allowing more distal penetration compared to commercial liquid embolics that react with the environment.
Documented Applications
Occlusion of the vasculature for treatment of tumors including meningioma and peripheral tumors.
Pre-surgical embolization of tumors to minimize blood loss.
Treatment of chronic subdural hematoma.
Treatment of brain aneurysms, arteriovenous malformations, and arteriovenous fistulas.
Gastrointestinal bleeds and bleeding due to trauma.
Prostate artery embolization.
Uterine artery embolization.
Treatment of visceral aneurysms, varicocele, and varices.
Treatment for pelvic congestion.
Treatment of epistaxis.
Treatment of endoleaks.
Portal vein embolization for redirecting blood flow and promoting hypertrophy prior to hepatic resection.
Endovascular embolization via the middle meningeal artery for chronic subdural hematoma and related diseases.
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