Polyphosphate-functionalized inorganic nanoparticles as hemostatic compositions and methods of use
Inventors
Kudela, Damien • Stucky, Galen D. • May-Masnou, Anna • Braun, Gary Bernard • Morrissey, James H. • Smith, Stephanie A.
Assignees
University of California San Diego UCSD • University of Illinois System
Publication Number
US-12350399-B2
Publication Date
2025-07-08
Expiration Date
2034-03-07
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Abstract
A hemostatic composition is provided. The hemostatic composition includes a hemostatically effective amount of a hemostatic agent that includes a nanoparticle and a polyphosphate polymer attached to the nanoparticle. Also provided are medical devices and methods of use to promote blood clotting.
Core Innovation
The invention provides hemostatic compositions comprising a hemostatically effective amount of a hemostatic agent that includes a nanoparticle with a polyphosphate polymer attached to it. The nanoparticle may be made of various inorganic materials such as silica, diatomaceous earth, titanium dioxide, calcium hydroxyapatite, or gold, and the polyphosphate polymer may consist of chains of phosphate monomers, for example, with an average length of about 70 or 700 monomers. The composition can further include a protecting agent, such as polyethylene glycol (PEG), attached to the nanoparticle/polyphosphate by an enzymatically-cleavable linker to modulate activity.
The background outlines the critical need for rapidly effective hemostatic agents capable of arresting severe bleeding that can result in death within minutes. This is particularly challenging in battlefield or remote scenarios where immediate access to medical assistance is not available. Existing hemostatic methods and compositions require improvement in rapid initiation of blood clotting, clot strength, and reduction of adverse effects, and their application without need for intensive training or equipment.
The invention addresses these challenges by developing compositions where nanoparticles functionalized with polyphosphate polymers promote blood clotting effectively through mechanisms activating different coagulation cascade factors. The nanoparticle may induce clotting via activation of Factor XII, while polyphosphate promotes activation of Factor Xa and thrombin generation, leading to faster and stronger clot formation. The protecting agent with a cleavable linker allows for controlled activation at the hemorrhage site, potentially reducing systemic side effects.
Claims Coverage
The patent includes one independent method claim that covers administering a hemostatic agent to a subject and magnetically tracking its movement to a wound. The following inventive features are identified from the claims.
Hemostatic agent comprising a magnetic nanoparticle with attached polyphosphate polymer
The method involves administering a hemostatic agent including a magnetic nanoparticle attached to a polyphosphate polymer to a subject for wound treatment.
Magnetic tracking of the hemostatic agent movement to the wound
The method includes magnetically tracking the movement of the magnetic nanoparticle component of the hemostatic agent to the wound, which may involve imaging techniques.
Hemostatic agent with optional dye precursor for fluorescent tracking
The hemostatic agent may contain a dye precursor convertible to a fluorescent dye by a coagulation factor such as thrombin, enabling fluorescence-based tracking at the wound site.
Magnetic nanoparticle composition with specific core and shell materials
The magnetic nanoparticle may comprise a silver core and silica shell, or materials selected from iron oxide, diatomaceous earth, aluminosilicate, transition metal oxides, and titanium dioxide.
Hemostatic agent including a protecting agent attached to the magnetic nanoparticle
The hemostatic agent can further include a protecting agent such as polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA), polypropylene glycol, or combinations thereof, attached to the magnetic nanoparticle.
The independent claim covers a method of treating a wound by administering a hemostatic agent comprising a magnetic nanoparticle with attached polyphosphate polymer and includes features for magnetic and fluorescent tracking, specific nanoparticle materials, and optional protecting agents, providing a multifunctional hemostatic and trackable therapeutic system.
Stated Advantages
The hemostatic compositions provide rapid initiation of blood clotting and improved clot strength.
The compositions are effective under coagulopathic conditions such as dilution and hypothermia.
The presence of the protecting agent with enzymatically-cleavable linkers allows targeted activation at hemorrhage sites, reducing off-target effects.
Functionalization of nanoparticles with polyphosphate enhances hemostatic activity compared to nanoparticles or polyphosphate alone.
Magnetic nanoparticles allow for non-invasive tracking of the hemostatic agent to the wound site.
Documented Applications
Treatment of bleeding wounds including severe external and internal hemorrhages.
Use in battlefield or remote settings where rapid, safe, and easy application of hemostatic agents is needed.
Medical devices such as bandages, gauze, or sponges coated with hemostatic compositions for topical application.
Intravenous administration of protected hemostatic agents for internal hemorrhages with enzymatic activation at the bleeding site.
Tracking and imaging of hemostatic agent localization using magnetic and fluorescent properties.
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