Embolic compositions and methods
Inventors
Groom, Jeffrey • WILTSEY, Craig • Pham, Quynh • MANSUKHANI, Nikhita • Guertin, Courtney • Core, Lee • Sharma, Upma
Assignees
Publication Number
US-12296065-B2
Publication Date
2025-05-13
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 biocompatible crosslinkable compositions, kits, and methods for forming and delivering such compositions in situ, specifically for applications such as embolization of vasculature, including neurovasculature. The compositions are based on mixtures containing polysiloxanes with two or more unsaturated groups (such as vinyl-terminated PDMS), silica fillers, imaging agents like bismuth trioxide, hydride materials with two or more hydride groups, and a catalyst to facilitate crosslinking between unsaturated and hydride groups. The inventions further encompass kits configured with suspensions for mixing these components and delivering the crosslinkable compositions directly to the target site within a patient.
The problem being addressed by this invention is the need for compositions that can be delivered and cured in situ within challenging, closed, or difficult-to-access body sites, such as the vasculature, particularly for vascular and neurovascular embolization procedures. Existing materials may lack properties such as the ability to fill complex and empty or blood-filled spaces, achieve precise support of tissues, or provide optimal injectability and imaging characteristics needed for successful and safe embolization.
The solutions presented involve designing solvent-free, shear-thinning, and flow-responsive polymer-based compositions that crosslink after delivery, allowing for distal penetration, filling, and occlusion of targeted vasculature with controlled viscosity and curing. The invention further details multiple configurations of kits and methods for preparation—including mixing dry and fluid components at the time of use—and delivery via catheters or needles, enabling tailored viscosity, radiopacity, and mechanical behavior of the in situ cured material.
Claims Coverage
The patent contains three independent claims defining inventive features for kits designed to form crosslinkable compositions for vascular embolization. Each claim outlines main structural and compositional elements needed to form the crosslinked embolic compositions.
Kit comprising first and second suspensions and dry composition for crosslinkable embolic composition
A kit includes: - A first suspension containing a first crosslinkable polymer and a first imaging agent (where the imaging agent is bismuth trioxide). - A second suspension comprising a crosslinker and, optionally, a second imaging agent (bismuth trioxide, same or different from the first imaging agent). - A dry composition containing a first filler and optionally a second filler (which can be the same or different). When these three components are mixed, they provide a crosslinkable composition in which at least a portion of the first and second imaging agents are dispersed.
Kit comprising polysiloxane with unsaturated groups, hydride material, and silica filler
A kit includes: - A first suspension containing a polysiloxane having two or more unsaturated groups and a first imaging agent with an average primary particle size from 80 nm to 200 nm (bismuth trioxide). - A second suspension containing a hydride material with two or more hydride groups and, optionally, a second imaging agent (bismuth trioxide, with the same particle size criteria). - A dry composition comprising a first silica filler and, optionally, a second silica filler. Mixing these components yields a crosslinkable composition with at least a portion of the imaging agents dispersed.
Kit comprising crosslinkable polymer and bismuth trioxide with silica fillers
A kit includes: - A first suspension of a crosslinkable polymer and bismuth trioxide, with particle size from 80 nm to 200 nm. - A second suspension of a crosslinker and, optionally, bismuth trioxide (same particle size). - A dry composition with a first silica filler and optionally a second silica filler. Combining these produces a crosslinkable composition having bismuth trioxide from both suspensions at least partially dispersed within the composition.
In summary, the claims establish kit configurations involving suspensions of crosslinkable polymers, crosslinkers, and imaging agents such as bismuth trioxide, combined with silica fillers, formulated such that upon mixing, a crosslinkable composition suitable for vascular embolization is provided.
Stated Advantages
The compositions can be delivered in-situ to closed cavities, such as intravascularly, and to difficult-to-access body sites.
In-situ-forming crosslinked compositions are capable of filling empty space, potential space, or space filled with blood, supporting surrounding tissues.
The compositions exhibit shear-thinning and flow-responsive properties, enabling distal penetration, proximal control, and substantially complete fill and occlusion of targeted vasculature when injected.
Compositions are radiopaque due to the presence of imaging agents such as bismuth trioxide, allowing real-time visualization during embolization.
Mixing dry components with fluids at the time of injection maximizes shear thinning, reducing injection force required and allowing for hand injection.
The compositions are biocompatible and demonstrate minimal inflammation, absence of vessel injury, and non-cytotoxicity based on histopathological analysis.
Hydrophobic or hydrophilic silica fillers can be selected to optimize stability and injectable properties of the mixture.
Compositions support terminal sterilization by various methods, including electron-beam irradiation, depending on the molecular weight of the silicone components.
Documented Applications
Embolization of vasculature, including neurovascular embolization, portal vein embolization, embolization of tumors, pre-surgical embolization of tumors, chronic subdural hematoma, brain aneurysms, arteriovenous malformations, arteriovenous fistulas, gastrointestinal bleeds, bleeding due to trauma, prostate artery embolization, uterine artery embolization, visceral aneurysms, varicocele, varices, pelvic congestion, epistaxis, and treatment of endoleaks.
Injection into the portal vein for portal vein embolization prior to hepatic resection.
Injection into the middle meningeal artery for treating chronic subdural hematoma, meningioma, dural arteriovenous fistula, pseudoaneurysm, true aneurysm, traumatic arteriovenous fistula, moyamoya disease, migraine, and meningioma.
Pre-surgical embolization of hypervascular brain tumors such as meningioma to reduce operative blood loss and surgery time.
Distal penetration and occlusion of small vessels (down to vessels less than 100 microns) using injection of the crosslinkable compositions.
Use in combination with occlusion devices, balloon catheters, and/or other intravascular devices such as coils, plugs, or stent grafts.
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