Embolic compositions and methods
Inventors
Groom, Jeffrey • WILTSEY, Craig • Pham, Quynh • MANSUKHANI, Nikhita • Guertin, Courtney • Core, Lee • Sharma, Upma
Assignees
Publication Number
US-11844870-B2
Publication Date
2023-12-19
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 provides biocompatible, crosslinkable compositions, kits, and methods for forming crosslinked compositions in situ, specifically designed for vascular embolization. These compositions include components such as polysiloxanes having two or more unsaturated groups, hydride materials having two or more hydride groups, silica fillers, imaging agents (notably bismuth trioxide of defined particle size), catalysts, and optional additives such as plasticizers, silanol compounds, and physical crosslinking agents.
The problem addressed by this invention is the need for embolic materials that can be delivered in-situ to complex or difficult-to-access regions of the vasculature with superior filling, occlusion, and support properties. Conventional crosslinkable compositions lack optimal flow responsiveness, distal penetration, and control during injection, leading to suboptimal embolization and potential adverse effects such as non-target embolization, vessel constriction, or recanalization.
The disclosed crosslinkable compositions are designed to exhibit shear-thinning properties and can be formulated by mixing fluid and dry components, optionally with annealing steps, immediately prior to use. Upon injection—such as by hand through a catheter—these compositions flow into and fill distal vessels, including those under 100 microns in diameter, and subsequently cure to form a solid occlusion. The system allows for flexibility in formulation (pre-mixed or mixed at the time of use), control over injection force, and even dispersion of silica and imaging agents for predictable clinical performance.
Claims Coverage
The independent claim focuses on a method comprising specific steps and material compositions for vascular embolization, encompassing multiple inventive features.
Formation of crosslinkable composition by annealing and mixing defined fluid and dry components
The method involves: 1. Annealing a first fluid composition comprising a first polysiloxane with two or more unsaturated groups and bismuth trioxide (80–200 nm particle size). 2. Annealing a second fluid composition comprising a hydride material with two or more hydride groups and bismuth trioxide (80–200 nm). 3. Mixing both annealed fluid compositions with a dry composition that contains a first silica filler (and optionally a second silica filler), thereby producing a crosslinkable composition in which bismuth trioxide and silica fillers are substantially evenly dispersed.
Delivery system and injection methodology for vascular occlusion
The crosslinkable composition is: - Placed in a syringe of at least 1 mL volume attached to a catheter with a lumen diameter of at least 0.016 inches. - Injected by hand into a patient’s vasculature. - The composition substantially flows into and occludes a plurality of distal vessels, including at least one vessel of less than 100 microns in diameter, and subsequently crosslinks in situ to form a solid occlusion.
The inventive features collectively cover a process for preparing a crosslinkable, embolic composition comprising defined steps of component preparation (including annealing and mixing), defined material characteristics (particle sizes, composition), and a method of by-hand injection into the vasculature resulting in distal vessel occlusion and in situ solidification.
Stated Advantages
Ability to deliver in-situ-forming crosslinked compositions to closed cavities, including difficult-to-access body sites and intravascularly.
Provides flow-responsive, shear-thinning materials for distal penetration and proximal control during injection, enabling complete fill and occlusion of targeted vasculature.
Supports surrounding tissues by filling empty, potential, or blood-filled spaces within the vasculature.
Even suspension of imaging agents due to structured fluid or paste nature allows for homogeneous radiopacity or imaging during injection.
Compositions are injectable by hand, offering a controllable and tactile delivery experience for clinicians.
Crosslinked compositions provide good biocompatibility and induce minimal to mild inflammation and no vessel injury or necrosis in vivo.
Compositions can penetrate and occlude very small, distal vessels, including those less than 100 microns in diameter.
Materials are suitable for terminal sterilization, including e-beam, depending on formulation.
Material properties (injectability, viscosity, coalescence, etc.) can be tuned by preparation method and component selection.
Using bismuth trioxide as radiopaque agent reduces risks associated with traditional agents (e.g., flammability) and improves visibility for surgical resection.
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, trauma-induced bleeding, abdominal aortic aneurysm, intracranial aneurysm, pulmonary aneurysm, or hemorrhage.
Prostate artery embolization.
Uterine artery embolization.
Treatment of visceral aneurysms, varicoceles, or varices.
Treatment for pelvic congestion.
Treatment of epistaxis.
Treatment of endoleaks.
Portal vein embolization to increase the size of the future liver remnant before hepatic resection.
Embolization of the middle meningeal artery for diseases such as dural arteriovenous fistula, pseudoaneurysm, true aneurysm, traumatic arteriovenous fistula, moyamoya disease, recurrent chronic subdural hematoma, migraine, and meningioma.
Embolization in conjunction with other devices such as coils, plugs, or stent grafts.
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