Anticoagulant compounds and methods and devices for their use
Inventors
Sirhan, Motasim • Zheng, Xiaoxia • Bhat, Vinayak D. • Yan, John
Assignees
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Publication Number
US-12521258-B2
Publication Date
2026-01-13
Expiration Date
Abstract
Devices, systems, and methods are provided including a structure having one or more surfaces configured for internal use within a patient's body and one or more therapeutic compositions comprising one or more active substances including a direct factor Xa inhibitor, and a direct factor IIa inhibitor disposed in or on the structure. The structure is configured to be positioned adjacent an injury site in the patient's body. The one or more active substances optionally include an anti-proliferative agent. The therapeutic composition is formulated to release the one or more active substances to the injury site to provide one or more of inhibit clot formation, promote clot dissolution, inhibit or dissolute inflammation, inhibit vessel injury, increase time before clotting, and/or inhibit cell proliferation.
Core Innovation
The disclosure describes an implantable scaffold configured for placement and expansion in a mammal's vasculature. The scaffold carries a direct factor IIa inhibitor comprising argatroban and a direct factor Xa inhibitor comprising apixaban or rivaroxaban disposed over at least part of the structure. The inhibitors are present in amounts that synergistically reduce blood clot formation while maintaining specified adjacent-tissue concentrations and weight compositional ratios. Certain scaffold embodiments additionally incorporate an anti-proliferative agent comprising an mTOR inhibitor or paclitaxel.
Embodiments provide controlled local drug release through surface coatings, reservoirs, or polymeric carriers to limit systemic exposure. The delivery configuration applies to vascular scaffolds, drug-coated balloons, vascular catheters, surgical instruments, and valve implants. These structures reduce fibrin deposition, blood clot formation, and smooth-muscle-cell proliferation while supporting anti-proliferative activity. Optional embodiments further incorporate an antiplatelet drug.
Claims Coverage
The three independent claims are claims 1, 6, and 23, defining three inventive features directed to implantable vascular scaffolds carrying direct factor IIa and factor Xa inhibitors alone or in combination with an anti-proliferative agent.
Scaffold carrying direct factor IIa and factor Xa inhibitors
Claim 1 covers a scaffold structure configured to be implanted and expanded in a mammal's vasculature, carrying argatroban and apixaban or rivaroxaban disposed over at least part of the structure. The inhibitors generate an adjacent tissue concentration of about 0.2 ng/mg to about 100 ng/mg within about 3 hours to about 28 days, synergistically reduce blood clot formation, and maintain a factor Xa to factor IIa weight compositional ratio of about 1:1 to about 1:3.
Scaffold carrying inhibitors and an anti-proliferative agent
Claim 6 covers an implantable vascular scaffold carrying argatroban, apixaban or rivaroxaban, and an anti-proliferative agent disposed over at least part of the structure. The inhibitors generate an adjacent tissue concentration of 0.2 ng/mg to 100 ng/mg within about 3 hours to about 28 days, synergistically reduce blood clot formation, and have a factor Xa to factor IIa weight compositional ratio of about 1:1 to about 1:3.
Scaffold carrying inhibitors and a specified anti-proliferative agent
Claim 23 covers an implantable vascular scaffold carrying argatroban, apixaban or rivaroxaban, and a specified anti-proliferative agent comprising an mTOR inhibitor or paclitaxel, or a stated form thereof. The factor IIa and factor Xa inhibitors generate an adjacent tissue concentration of 0.2 ng/mg to 100 ng/mg within about 3 hours to about 28 days, synergistically reduce blood clot formation, and maintain a factor Xa to factor IIa weight compositional ratio of about 1:1 to about 1:3.
The independent claims center on vascular scaffolds combining direct factor IIa and direct factor Xa inhibitors to synergistically reduce blood clot formation under specified concentration, timing, and weight ratio limitations. Claims 6 and 23 further require an anti-proliferative agent, with claim 23 specifying an mTOR inhibitor or paclitaxel.
Stated Advantages
The combination of direct factor IIa and factor Xa inhibitors synergistically reduces blood clot formation and improves clot and fibrin inhibition.
In reported porcine stent studies, rivaroxaban alone reduced fibrin at day 7, while rivaroxaban combined with argatroban reduced fibrin and smooth-muscle-cell proliferation.
Combining an anti-proliferative agent such as sirolimus or other mTOR inhibitors with the direct factor IIa and factor Xa inhibitors shows improved outcomes and enhances anti-proliferative activity compared with mTOR-inhibitor controls.
Local delivery of the therapeutic agents from the scaffold reduces systemic exposure.
Documented Applications
Local delivery of direct factor IIa and factor Xa inhibitors from implantable scaffolds or stents in a mammal's vasculature, optionally in combination with an anti-proliferative agent or an antiplatelet drug.
Treatment of vascular injury and blockage using vascular scaffolds, stents, or drug-coated balloons.
Drug-delivery embodiments for drug-coated balloons, vascular catheters, surgical instruments, valve implants, and covered-stent sleeves.
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