Embolic compositions and methods
Inventors
Groom, Jeffrey • WILTSEY, Craig • Pham, Quynh • MANSUKHANI, Nikhita • Guertin, Courtney • Core, Lee • Sharma, Upma
Assignees
Publication Number
US-12029830-B2
Publication Date
2024-07-09
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 present invention addresses the need for in-situ-forming crosslinkable compositions that are biocompatible and capable of embolizing vasculature, including neurovasculature and other body sites. The compositions are designed to be delivered as flowable fluids, which upon mixing form a crosslinkable system that cures within the body to occlude targeted vessels.
The solution comprises kits and methods based on mixing a first fluid composition (containing a crosslinkable polymer such as polysiloxane with unsaturated groups and bismuth trioxide as an imaging agent) with a second fluid composition (containing a crosslinker, such as a hydride material with two or more hydride groups, and bismuth trioxide), and a dry composition comprising hydrophobic silica fillers. Once mixed, these components form a crosslinkable, shear-thinning composition that can be injected and flow into even very small distal vessels before curing into a solid for vascular occlusion.
The disclosed compositions achieve advantages such as effective space filling, ease of delivery via catheter or needle to difficult-to-access body sites, support of surrounding tissue, and complete occlusion of small vessels. The methods and kits also enable controlled mixing and delivery, compatibility with imaging modalities, and the tailoring of viscosity and cure profiles to clinical needs.
Claims Coverage
There are two independent claims in this patent, each directed to methods for forming and delivering a crosslinkable composition for vascular embolization with specific compositional and procedural features.
Formation and injection of crosslinkable embolic composition with bismuth trioxide and hydrophobic silica filler
A method involving: - Forming a crosslinkable composition by providing a first fluid composition with a crosslinkable polymer and bismuth trioxide (average primary particle size 80–200 nm), and a second fluid composition with a crosslinker and bismuth trioxide (average primary particle size 80–200 nm). - Mixing both fluid compositions with a dry composition containing hydrophobic first silica filler and optionally a hydrophobic second silica filler. - Achieving substantially even dispersion of bismuth trioxide and silica fillers in the crosslinkable composition. - Preparing and injecting the composition into a vascular injection site so that it flows into, and occludes, a plurality of distal vessels (including at least one vessel under 100 microns diameter), then crosslinks to form a solid.
Minimum bismuth trioxide content in both fluid compositions for vascular embolization
A method as described above, further specifying: - The crosslinkable composition must comprise at least 10 wt% bismuth trioxide in each of the first and second fluid compositions. - All steps from formation to injection and occlusion of distal vasculature as in the main method claim.
The inventive features focus on the unique combination of crosslinkable polymers, bismuth trioxide as imaging agent at specified particle sizes and concentrations, hydrophobic silica fillers, and their even dispersion to enable shear-thinning, flow-responsive injection and in vivo curing for effective distal vascular embolization.
Stated Advantages
The compositions enable in-situ formation of crosslinked occlusive materials that can be delivered via catheter or needle even to difficult-to-access sites.
Shear-thinning properties allow the composition to flow and fill distal vasculature, providing complete vascular casting and occlusion down to vessels less than 100 microns in diameter.
The inclusion of imaging agents such as bismuth trioxide imparts radiopacity, supporting real-time imaging and precise delivery.
Optimized viscosity and injection force allow for hand injectable delivery, broadening clinical usability.
The compositions are biocompatible and non-cytotoxic, with minimal to mild inflammation and absence of necrosis or vessel injury based on histopathological analysis.
Pre-mixing and the use of certain fillers and preparation methods can stabilize viscosity, minimize injection force, and control the formulation's physical properties for improved handling and performance.
Ability to finely tailor material properties, including ductility, elasticity, and coalescence, for specific clinical requirements.
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.
Treatment of gastrointestinal bleeds and bleeding due to trauma.
Prostate artery embolization and uterine artery embolization.
Treatment of visceral aneurysms, varicoceles, and varices.
Treatment for pelvic congestion.
Treatment of epistaxis.
Treatment of endoleaks.
Portal vein embolization procedures.
Embolization procedures in the neurovasculature, such as into the middle meningeal artery (MMA) for conditions like dural arteriovenous fistula, aneurysms, and chronic subdural hematoma.
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