Silica fiber hemostatic device and method

Abstract

Embodiments of the present invention include hemostatic compositions, delivery devices, kits, and methods that utilize silica fibers or other silica fiber compositions. The fiber compositions can be formed via electrospinning of a sol-gel generated with a silicon alkoxide reagent, such as tetraethyl orthosilicate, an alcohol solvent, and an acid catalyst. The present invention provides compositions, kits, and methods for treating bleeding (exsanguination) in a subject. In various aspects, the present invention provides compositions comprising electrospun silica fibers that can rapidly stop bleeding when applied to the site of bleeding.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 898,148, filed September 10, 2019, and U.S. Provisional Patent Application No. 63 / 002,475, filed March 31, 2020, the entire disclosures of each of which are hereby incorporated by reference herein.

[0002] In various embodiments, the present invention relates to hemostatic devices and methods that utilize silica fibers. [Background technology]

[0003] Excessive bleeding or hemorrhage is a significant cause of mortality following trauma and battlefield injuries. Hemorrhage is also a complication during surgical procedures. The purpose of hemostatic products and processes is to aid in the rapid initiation of a hemostatic plug formed through platelet activation, aggregation, adhesion, and loose clot formation at the tissue target site.

[0004] A wide range of hemostatic products are made from a variety of matrices (e.g., collagen, gelatin, cellulose, chitosan, and fibrin), but these materials do not work for many applications, such as internal bleeding, where direct pressure to the wound is difficult or impossible.

[0005] SUMMARY OF THE DISCLOSURE In various aspects and embodiments, the present invention provides a hemostat for rapid control of bleeding, as well as methods and kits for using the same. Summary of the Invention

[0006] The present invention provides compositions, kits, and methods for treating bleeding (exsanguination) in a subject. In various aspects, the present invention provides compositions comprising electrospun silica fibers that can rapidly stop bleeding when applied to the site of bleeding. Thus, the present invention provides hemostatic devices and methods useful for treating severely injured subjects, including emergency treatment at the site of injury. The present invention is further useful in surgical settings for managing bleeding during surgery. In various embodiments, the present invention is used to treat trauma and injuries of various severity. Also provided in embodiments of the present invention are delivery devices for hemostatic devices and materials.

[0007] Electrospun silica material can retain many times its weight in water (e.g., typically more than 50 times its weight in water). As a result, the material can absorb large amounts of blood, but blood cells cannot penetrate, and a physical barrier quickly forms. In various embodiments, the silica fiber composition enhances the clotting pathway. The silica fiber material may be applied as a flocculent material, or alternatively, as a powder or dust, gel, paste, or additive to a flowable matrix.

[0008] In some embodiments, the silica fiber composition is a lightweight structure consisting essentially of silica fibers (e.g., silicon dioxide nanofibers). In various embodiments, the fiber composition consists essentially of SiO2 (i.e., contains only SiO2 and unintentional impurities), and in some embodiments, consists of species and / or complexes resulting from incomplete conversion of the sol to SiO2 (e.g., water and / or chemical groups such as ethoxyl groups, silanol groups, hydroxyl groups, etc.). The composition may be formed from a gelatinous material that is electrospun to form a fiber mat (e.g., a nonwoven mat). For example, the composition may be prepared by electrospinning a sol-gel. A typical sol-gel is prepared with a silicon alkoxide reagent, such as tetraethyl orthosilicate (TEOS), an alcohol solvent, and an acid catalyst. In various embodiments, the sol is transformed under controlled humidity and temperature conditions for at least 2 days (and in various embodiments, less than 7 days). The sol-gel is electrospun to form a silica fiber mat with excellent texture and properties, which may be used as or in a hemostatic device. The fibers may be of variable diameter (eg, ranging from about 50 nm to 5 μm).

[0009] The material may be used as a fiber mat portion that is folded and / or agglomerated to prepare a suitable mass of material for enveloping a site of heavy bleeding (including bleeding in a body cavity). In some embodiments, the silica fiber material is processed into a loosely agglomerated, flocculent material, which may be formed by chopping and / or agglomerating a portion of the electrospun fiber mat. In some embodiments, the silica fiber material is provided with a material that facilitates handling and application to the wound site (e.g., any suitable backing material or flexible container). Alternatively, the silica fiber material may be applied as a powder or dust, gel, paste, or as an additive to a flowable matrix, and such compositions may optionally include one or more fillers. Exemplary fillers include, but are not limited to, various synthetic and natural polymers.

[0010] In some embodiments, the fiber composition is applied directly to the site of bleeding by wrapping the site with the material in any form and applying as much pressure as possible. The fiber composition absorbs blood and large amounts of fluid, but blood cells cannot enter the material, and a physical barrier against further blood loss is quickly formed. In various embodiments, blood or extracellular matrix proteins may bind to the material and help form a barrier, providing additional benefits such as reducing pain and facilitating healing. In some embodiments, even in cases of severe bleeding (e.g., grade 3 or 4 bleeding), the silica fiber material can stop blood flow within about 60 seconds, or in some embodiments, within about 30 seconds, or in some embodiments, within about 15 seconds. By quickly stopping severe bleeding at the site of injury, the patient can be transported to a surgical facility more quickly and safely. The silica fiber material can be easily removed by the physician during surgery.

[0011] In some embodiments, the bleeding is occurring during or after a surgical procedure. In some embodiments, the bleeding is traumatic bleeding, e.g., non-compressible bleeding. In various embodiments, the bleeding is the result of a crush injury, a gunshot wound, or a blast wound.

[0012] Other useful applications include nosebleeds and wounds, for example, the silica fiber material may be formed into pads or bandages or used in conjunction with various types of conventional bandage materials (e.g., cotton gauze) and / or wound dressings to aid in bleeding control.

[0013] Other aspects and embodiments of the invention will be apparent from the following non-limiting examples.

[0014] In one aspect, embodiments of the invention feature a method for treating a bleeding in a subject, the method including, consisting essentially of, or consisting of applying a silica fiber composition (e.g., an electrospun silica fiber composition) to said bleeding in an amount and under conditions sufficient to stop or slow the bleeding.

[0015] Embodiments of the invention may include one or more of the following in any of various combinations. The composition may be prepared by electrospinning a sol. The sol may be prepared with tetraethyl orthosilicate (TEOS). The sol may include 70%-90% by weight TEOS, 8%-25% by weight ethanol, an acid catalyst, and the balance water. The sol may include 70%-90% by weight TEOS, 8%-25% by weight ethanol, 1%-10% by weight water, and an acid catalyst. The sol may include 75%-85% by weight TEOS, 12%-20% by weight ethanol, and about 2%-5% by weight water. The sol may include about 80% by weight TEOS, about 17% by weight ethanol, and about 3% by weight water. The acid catalyst may include, consist essentially of, or consist of HCl. The sol may include less than about 0.1% by weight acid catalyst. The sol may contain 0.02% to 0.08% by weight of an acid catalyst.

[0016] The sol may be allowed to transition for at least 2 days under conditions with humidity ranging from about 40% to about 80% and temperature ranging from 50°F to 90°F. The sol may be allowed to transition for at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days. The sol may be allowed to transition for 2 to 7 days. The sol may be electrospun when the weight is 20% to 40% of the starting weight before aging (transition). The sol may be electrospun when the ethylene vapor production is 10% to 20% of the peak production of ethylene vapor during aging (transition). The sol may be electrospun when the ethylene vapor production therefrom is 10% to 40% of the sol before aging (transition). The sol may not be exposed to heat in excess of 150°F or 100°F. The fibers of the silica fiber composition may be of variable diameter from about 50 nm to about 5 μm. The fibers may be of variable diameter from about 200 nm to about 1000 nm. The composition may comprise, consist essentially of, or consist of SiO2. The composition may be electrospun with a thickness of about ⅛ inch to about ¼ inch. The composition may be electrospun with a thickness of greater than about ⅛ inch or greater than about ¼ inch. The fiber composition may comprise, consist essentially of, consist of, or be processed into a powder or dust or a plurality of fiber pieces.

[0017] The subject may be a mammal. The subject may be a veterinary patient, e.g., a dog, a cat, or a horse. The subject may be a human patient. The bleeding may be at least a grade 2 bleeding, e.g., a grade 3 or grade 4 bleeding. The bleeding may be arterial bleeding. The bleeding may be venous bleeding. The bleeding may be a runoff during or after a surgical procedure. The bleeding may be organ bleeding. The bleeding may be primary bleeding. The bleeding may be rebound bleeding. The bleeding may be secondary bleeding. The bleeding may be traumatic bleeding. The bleeding may be non-compressible bleeding. The bleeding may be a body cavity bleeding. The injury may be a crush injury, a gunshot wound, or a blast injury. The bleeding may be a nosebleed. The bleeding may be external to the subject. The subject may be undergoing treatment to inhibit the coagulation pathway. The subject may have a coagulation disorder. The subject may have hemophilia, thrombocytopenia, low platelet count, or von Willebrand's disease.

[0018] The silica fiber composition may be applied to the bleeding via a delivery device. The delivery device may include, consist essentially of, or consist of a hollow central bore, a movable plunger, and an annular outer compartment coaxial with the central bore. The central bore may have an upper end and an open lower end. The plunger may be located at the upper end of the central bore. The plunger may be actuable by a user of the delivery device to push the silica fiber composition out of the open lower end of the central bore. A portion of the plunger may separate the central bore into a lower compartment and an upper compartment. The external compartment may be fluidly connected to the upper compartment of the central bore. The external compartment may define one or more openings for fluidly connecting with an area proximate to the bleeding. When the plunger is actuated to push the silica fiber composition out of the open lower end of the central bore and into the bleeding, fluid proximate to the bleeding may be simultaneously aspirated into the external compartment and into the upper compartment of the central bore. The central bore may define one or more openings therethrough that fluidly connect the lower compartment to the annular outer compartment.

[0019] In another aspect, an embodiment of the invention features a delivery device for applying a silica fiber composition proximate to a bleeding. The delivery device includes, consists essentially of, or consists of a hollow central bore, a movable plunger, and an annular outer compartment coaxial with the central bore. The central bore has an upper end and an open lower end. The plunger is disposed at the upper end of the central bore. The plunger is actuable by a user of the delivery device to force the silica fiber composition out of the open lower end of the central bore. A portion of the plunger separates the central bore into a lower compartment and an upper compartment. The outer compartment is fluidly connected to the upper compartment of the central bore. The outer compartment defines one or more openings for fluidly connecting with an area proximate to the bleeding. When the plunger is actuated to force the silica fiber composition out of the open lower end of the central bore and into the bleeding, fluid proximate to the bleeding is simultaneously aspirated into the outer compartment and into the upper compartment of the central bore.

[0020] Embodiments of the invention may include one or more of the following in any of various combinations: The central bore may define one or more openings therethrough fluidly connecting the lower compartment to the annular outer compartment; A silica fiber composition may be disposed within the lower compartment of the central bore; The silica fiber composition may include, consist essentially of, or consist of a plurality of silica fibers; The silica fiber composition may include, consist essentially of, or consist of a powder or dust.

[0021] In yet another aspect, an embodiment of the invention features a kit for treating bleeding in a subject, the kit including, consisting essentially of, or consisting of a silica fiber composition and a delivery device.

[0022] An embodiment of the invention may include one or more of the following in any of various combinations: The delivery device may include, consist essentially of, or consist of a hollow central bore, a movable plunger, and an annular outer compartment coaxial with the central bore. The central bore may have an upper end and an open lower end. The plunger may be located at the upper end of the central bore. The plunger may be actuable by a user of the delivery device to force the silica fiber composition out of the open lower end of the central bore. A portion of the plunger may separate the central bore into a lower compartment and an upper compartment. The outer compartment may be fluidly connected to the upper compartment of the central bore. The outer compartment may define one or more openings for fluidly connecting with an area proximate the bleeding. When the plunger is actuated to force the silica fiber composition out of the open lower end of the central bore and into the bleeding, fluid proximate the bleeding may be simultaneously aspirated into the outer compartment and into the upper compartment of the central bore. The central bore may define one or more openings therethrough that fluidly connect the lower compartment to the annular outer compartment. The silica fiber composition may include, consist essentially of, or consist of an electrospun silica fiber composition. The silica fiber composition may include, consist essentially of, or consist of a plurality of silica fibers. The silica fiber composition may include, consist essentially of, or consist of a powder or dust.

[0023] These and other objects, together with advantages and features of the invention disclosed herein, will become more apparent with reference to the following description, the accompanying drawings, and the claims. Moreover, it will be understood that the features of the various embodiments described herein are not mutually exclusive and may exist in various combinations and permutations. As used herein, the terms "approximately," "about," and "substantially" mean ±10%, and in some embodiments ±5%. The term "consisting essentially of" means excluding other materials that contribute to functionality, unless otherwise defined herein. Nevertheless, such other materials may be present in trace amounts, either collectively or separately.

[0024] In the drawings, like reference characters generally refer to the same parts throughout the various views. Also, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the following description, various embodiments of the invention are described with reference to the following drawings, in which: [Brief description of the drawings]

[0025] [Figure 1] FIG. 1A shows an embodiment of the invention using a gauze bag to facilitate handling of the silica fiber material; FIG. 1B shows an embodiment of the invention using a gauze backing to facilitate handling of the silica fiber material. [Diagram 2] FIG. 1 illustrates an embodiment of the present invention in which the silica fiber pad is shaped as a disk. [Diagram 3] 1A is a head-on view of an embodiment of a delivery device for applying a silica fiber composition to a wound site, FIG. 1B is a cross-sectional view of an embodiment of a delivery device for applying a silica fiber composition to a wound site, and FIG. 1C is a cut-away view of an embodiment of a delivery device for applying a silica fiber composition to a wound site. [Figure 4A] 1 is a scanning electron microscope (SEM) image of fibers spun according to the present disclosure. [Figure 4B] 1 is a scanning electron microscope (SEM) image of fibers spun according to the present disclosure. [Figure 4C] 1 is a scanning electron microscope (SEM) image of fibers spun according to the present disclosure. [Figure 4D] 4A-4D are scanning electron microscope (SEM) images of fibers spun according to the present disclosure. The images in Figures 4A-4D are at 50, 100, 200, and 500 micron scales, respectively. As shown, the fibers are soft, smooth, dense, and continuous (not fractured). [Figure 5A] FIG. 13 is an SEM image of fibers electrospun at a non-optimal time (before the sol-gel had fully matured). [Figure 5B] FIG. 13 is an SEM image of fibers electrospun at a non-optimal time (before the sol-gel had fully matured). [Figure 5C] FIG. 13 is an SEM image of fibers electrospun at a non-optimal time (before the sol-gel had fully matured). [Figure 5D] 5A-5D are SEM images of fibers electrospun at non-optimal times (before the sol-gel had fully matured). The images in Figures 5A-5D are at 50, 100, 200, and 500 micron scales, respectively. As can be seen, the fibers appear stiff and many fractures can be seen, with agglomerates forming. [Figure 6] SEM image of fibers spun at suboptimal times (20 micron scale shown). The fibers are stiff and fractures are evident. [Figure 7] 1 illustrates a fiber mat spun according to the present disclosure at a thickness of about ¼ inch. The mat is soft and pliable to the touch. [Figure 8] FIG. 1 compares a silica fiber mat electrospun upon sol-gel transfer according to the present disclosure shown in A with a fiber mat prematurely spun before the sol-gel had optimally matured shown in B. The material in A is soft to the touch, very flexible, and can be spun to a thickness that is easily handled for application of a fiber layer to the wound. The material in B is brittle, inflexible, and the fiber layer cannot be easily separated to cover the surface area of ​​the wound. [Figure 9A]1 is a histology image using hematoxylin and eosin staining of an arterial injury site in a porcine model treated with a silica fiber composition according to an embodiment of the present invention during a hemostatic study. [Figure 9B] 1 is a histology image using Martusius Scarlet Blue (MSB) trichrome fibrin staining of an arterial injury site in a porcine model treated with a silica fiber composition according to an embodiment of the present invention during a hemostatic study. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The present invention provides compositions and methods for treating bleeding (exsanguination) in a subject. In various aspects, the present invention provides compositions comprising electrospun silica fibers that can rapidly stop bleeding when applied to the site of bleeding. Thus, the present invention provides hemostatic devices and methods useful in treating subjects who have sustained severe injuries, including emergency treatment at the site of injury. The present invention is further useful in surgical settings for managing bleeding during surgical procedures. In various embodiments, the present invention is used to treat trauma and injuries of various severity.

[0027] Electrospun silica material can retain many times its weight in water (e.g., typically more than 50 times its weight in water). As a result, the material can absorb large amounts of blood, but blood cells cannot penetrate, and a physical barrier quickly forms. In some embodiments, the silica material binds to extracellular matrix proteins and / or serum proteins to aid in the formation of the barrier. In various embodiments, clotting is enhanced by the silica fiber composition. In the case of body cavity wounds, the silica fiber material may be filled or packed into the site of heavy bleeding and / or the body cavity. In some embodiments, the silica fiber material is applied more carefully and discriminately to the site of bleeding. The silica fiber material may be applied as a flocculent material, or alternatively, as a powder, dust, gel, paste, or additive to a flowable matrix.

[0028] In some embodiments, the silica fiber composition is a lightweight structure consisting essentially of silica fibers (e.g., silicon dioxide nanofibers). The composition may be formed from a gelatinous material that is electrospun to form a fiber mat (e.g., a nonwoven mat). For example, the composition may be prepared by electrospinning a sol-gel.

[0029] A typical sol-gel is prepared with a silicon alkoxide reagent, such as tetraethyl orthosilicate (TEOS), an alcohol solvent, and an acid catalyst. In various embodiments, the sol is transformed under controlled humidity and temperature conditions for at least 2 days (and in various embodiments, less than 7 days). The sol-gel is electrospun to form a silica fiber mat with excellent texture and properties, which can be used as or within a hemostatic device.

[0030] Known processes do not provide silica fiber compositions with sufficient flexibility for many applications, including wound care or health care applications. Instead, these structures are relatively brittle, hard, and dense. The mats easily crumble or break. The fiber layers are difficult to separate. And generally lack physical properties for use in health care applications. In various embodiments, to achieve a good material for tissue repair, it is important to electrospin the sol-gel once it has properly aged (or "transformed") to achieve a composition with the desired physical properties. By transitioning the sol under controlled environmental conditions and / or monitoring the preparation of the sol-gel during the aging process, a relatively short window of successful electrospinning of the sol-gel can be identified. According to embodiments of the present invention, the composition is not hard and has a soft feel similar to that of cotton.

[0031] The fibers may have variable diameters (e.g., ranging from about 50 nm to 5 μm). In some embodiments, the fibers are predominantly in the range of about 100 nm to about 2 μm, or predominantly in the range of about 200 to about 800 nm.

[0032] In some embodiments, a sol-gel for preparing a silica fiber composition is prepared by a method that includes preparing a first mixture that includes an alcohol solvent, a silicon alkoxide reagent such as tetraethyl orthosilicate (TEOS), preparing a second mixture that includes an alcohol solvent, water, and an acid catalyst, thoroughly titrating the second mixture into the first mixture, and treating (aging) the combined mixture under controlled environmental conditions to form a gel for electrospinning.

[0033] In some embodiments, the silicon alkoxide reagent is TEOS. Alternative silicon alkoxide reagents include those with the formula Si(OR)4, where R is 1-6, preferably 1, 2, or 3. In some embodiments, the alcohol solvent is anhydrous denatured ethanol, or in some embodiments, methanol, propanol, butanol, or any other suitable alcohol solvent. The first mixture may be stirred, for example, with a magnetic stirrer or similar stirring means. The second mixture includes an alcohol solvent, water, and an acid catalyst. The alcohol solvent in the second mixture may also be anhydrous denatured alcohol, or may be methanol, propanol, butanol, or any other suitably provided alcohol solvent. The water may be distilled water or deionized water. Sufficient acid catalyst is added to the mixture to aid in the reaction. The acid catalyst may be hydrochloric acid, or may be sulfuric acid, or other suitable acid catalyst. The second mixture may be stirred, for example, with a magnetic stirrer or other stirring means. In some embodiments, the first mixture (or sol) and the second mixture (or sol) are formed without the use of direct heat.

[0034] In some embodiments, the sol comprises about 70% to about 90% by weight of a silicon alkoxide (e.g., TEOS), about 5% to about 25% by weight of an alcohol solvent (e.g., absolute ethanol), an acid catalyst (e.g., less than about 0.1% by weight when using HCl), and the balance water.

[0035] In some embodiments, the sol comprises 70%-90% tetraethyl orthosilicate (TEOS), 8%-25% ethanol, 1%-10% water, and an acid catalyst. In some embodiments, the sol comprises 75%-85% TEOS, 12%-20% ethanol, and about 2%-5% water. A typical sol comprises about 80% TEOS, about 17% ethanol, and about 3% water. In some embodiments, the acid catalyst is HCl. For example, the sol may comprise less than about 0.1% HCl by weight. For example, the sol may comprise 0.02%-0.08% HCl by weight. In various embodiments, the sol is free of organic polymers or other substantial reagents such that the fiber composition is substantially pure SiO2. In various embodiments, the sol does not include inorganic salts (e.g., sodium chloride, lithium chloride, potassium chloride, magnesium chloride, calcium chloride, and / or barium chloride), and in various embodiments, inorganic salts are not mixed with other components of the sol or with the sol itself. In various embodiments, the fiber composition (and sol) does not include metals or metal oxides (e.g., TiO2 or ZrO2). In various embodiments, the fiber composition consists essentially of SiO2 (i.e., contains only SiO2 and unintentional impurities), and in some embodiments, consists of species and / or complexes resulting from incomplete conversion of the sol to SiO2 (e.g., water and / or chemical groups such as ethoxyl groups, silanol groups, hydroxyl groups, etc.).

[0036] According to various embodiments, the first mixture and the second mixture are mixed by dripping or titrating (preferably with stirring) the second mixture into the first mixture. The mixed mixture is then further processed by aging the sol in a controlled environment until a substantial portion of the alcohol solvent has evaporated to form a sol-gel suitable for electrospinning.

[0037] In various embodiments, the sol is not exposed to heat above 150° F. or above 100° F. to avoid accelerating the transition. The controlled environment may include an enclosure with at least one vent and optionally an exhaust fan to draw gas away from the mixture. The enclosure may have controlled conditions in terms of humidity, temperature, and optionally air pressure. For example, humidity may be controlled (e.g., with conventional humidifiers and / or dehumidifiers) to a range of about 30% to about 90%, such as about 40% to about 80%, or in some embodiments, about 50% to about 80%, or about 50% to about 70% (e.g., about 55%, or about 60%, or about 65%). Some humidity is useful to slow the evaporation of the solvent, thereby widening the window for successful electrospinning. In some embodiments, the temperature ranges from about 50°F to about 90°F, such as from about 60°F to about 80°F, or from about 65°F to about 75°F. In some embodiments, the air pressure is optionally controlled (e.g., with a low pressure vacuum source, such as a pump or fan). By controlling the environmental conditions during aging, the gel can be electrospun during the optimal spinning time, which may occur within a small window of only a few minutes if the aging process is accelerated too much (e.g., by direct heat). Aging the sol at a constant humidity of about 55% and a constant temperature of about 72°F will cause the sol to age (gelatinize) in a few days, and the window for successful electrospinning may extend to at least a few hours, and in some embodiments, up to a few days. In various embodiments, the aging process takes at least 2 days, or in some embodiments, at least 3 days. However, in various embodiments, aging does not exceed 10 days, nor does it exceed 7 days. In some embodiments, the aging process takes between 2 and 7 days, or between 2 and 5 days, or between 2 and 4 days (e.g., about 2, about 3, or about 4 days). In various embodiments, the sol-gel is well spinnable before it transitions to a more solid, non-flowable mass.

[0038] The enclosure space for aging the sol-gel may include a vent on at least one surface to exhaust gases from the enclosure, and optionally the vent may include a fan to exhaust gases generated during the aging process. The enclosure space may optionally include a heating source to provide a nominal amount of heat within the enclosure space to maintain a preferred temperature. In some embodiments, a source of humidity (e.g., an open container of water or other aqueous water-based liquid) is provided within the enclosure environment to regulate humidity to a desired range or value. The enclosure may further include one or more environmental monitors, such as a temperature reading device (e.g., a thermometer, thermocouple, or other temperature sensor) and / or a humidity reading device (e.g., a hygrometer or other humidity sensor).

[0039] In some embodiments, electrospinning of the sol-gel is performed after an aging process at controlled environmental conditions for at least 2 days, or at least 36 hours, or at least 3 days, or at least 4 days, or at least 5 days (but in various embodiments, at controlled environmental conditions for no more than 10 days or no more than 7 days). By slowing the aging process, the ideal time to spin the fibers can be identified. The weight of the sol-gel may be used as an indication of when the sol-gel is at or near the ideal time for electrospinning. Without wishing to be bound by theory, it is believed that the viscosity of the sol-gel is a poor determinant in identifying the optimal time for electrospinning. For example, in various embodiments, the sol-gel is about 10% to about 60% of the original weight of the sol (based on the loss of alcohol solvent during transition). In some embodiments, the sol-gel is in the range of 15-50% of the original weight of the sol, or about 20-40% of the original weight of the sol.

[0040] In some embodiments, the sol-gel is aged for at least 2 days, or at least 36 hours, or at least 3 days, or at least 4 days, or at least 5 days, and electrospun when the composition produces ethylene vapors that are in the range of about 10% to about 40%, such as in the range of about 10% to about 25%, such as in the range of about 10% to about 20%, of the vapors produced by the starting sol. Ethylene is a colorless, flammable gas with a faintly sweet, musky odor (noticeable due to slow solvent evaporation). Ethylene is produced by the reaction of ethanol with acid. Ethylene may optionally be monitored in the vapor using a conventional ethylene monitor. In other embodiments, the gases produced by the sol during the sol aging process are monitored to determine the preferred or optimal time for electrospinning. The gas profile may be monitored using gas chromatography.

[0041] Processing of the sol-gel mixture requires stirring or other agitation of the mixture at various intervals or continuously due to the formation of silicon dioxide crystalline material on the top surface of the mixture. This formation of crystalline material on the top surface slows down processing time and is believed to seal the exposure of the mixture to the gas vacuum provided within the enclosure space. In some embodiments, any solid crystalline material is removed from the mixture.

[0042] Once the sol-gel processing is complete, the sol-gel is then electrospun using any known technique. The sol or sol-gel may be stored (e.g., frozen or refrigerated) as needed (such time does not generally apply to aging times). Exemplary processes for electrospinning sol-gels are described in: Choi, Sung-Seen et al., "Silica nanofibers from electrospinning / sol-gel process," Journal of Materials Science Letters 22, 2003, 891-893, which is incorporated herein by reference in its entirety. Exemplary processes for electrospinning are further disclosed in U.S. Pat. No. 8,088,965, which is incorporated herein by reference in its entirety.

[0043] In a typical electrospinning technique, the sol-gel is placed in one or more syringe pumps fluidly coupled to one or more spinnerets. The spinnerets are connected to a high voltage (e.g., 5 kv-50 kv) source and are external to and point towards a grounded collector drum. The drum rotates along an axis of rotation that is generally perpendicular to the spinning direction, typically extending from the spinnerets to the drum, into the yarn. As the sol-gel is fed to the spinnerets from a syringe pump (or other storage tank), the high voltage between the spinnerets and the drum creates an electrically charged liquid jet that deposits on the drum as small entangled fibers. As the drum rotates and electrospinning continues, a fibrous mat of silica fibers forms along the periphery of the drum. In various embodiments, the spinnerets and syringe pump(s) may be placed on a moveable platform that can move parallel to the length of the drum. In this way, the length of the resulting fiber mat along the drum may be increased without increasing the number of spinnerets. The diameter of the drum may also be increased to increase the areal size of the electrospun mat. The thickness of the mat can depend largely on the amount of sol-gel used in spinning and therefore the electrospinning time. For example, the mat can be greater than about 1 / 8 inch in thickness, or greater than about 1 / 4 inch in thickness, or greater than about 1 / 3 inch in thickness, or greater than about 1 / 2 inch in thickness.

[0044] Silica fiber mats and compositions produced according to embodiments of the invention exhibit one or more useful properties when compared to fiber compositions spun at non-optimal times (e.g., due to improper aging of the sol-gel). For example, fiber mats and compositions according to embodiments of the invention do not burn, char, or visibly degrade when directly exposed to heat or open flame. In contrast, various fiber compositions spun at non-optimal times exhibit char and / or visible color change when exposed to sufficient heat or open flame. Fiber mats and compositions according to embodiments of the invention also effectively wick moisture (e.g., water or bodily fluids) and absorb such fluids into the fiber mat. In contrast, various fiber compositions spun at non-optimal times do not visibly absorb or wick moisture, even when directly applied. Such compositions tend to be hydrophobic. Finally, fiber mats and compositions according to embodiments of the invention are fluffy and can be easily molded to uneven, non-uniform, and / or non-flat (e.g., curved) surfaces or shapes without rupturing or losing structural integrity. Thus, such compositions can be easily applied or conformed to a variety of different surfaces. In contrast, various fiber compositions that are spun for non-optimal times tend to be flat, plate-like, brittle, and will at least partially fracture if subjected to excessive mechanical shaping or bending.

[0045] The fibrous layer can be easily separated from the mat, for example for application to a heavily bleeding tissue. In some embodiments, the composition is electrospun with a thickness of about 1 / 8 inch to about 1 / 2 inch. For example, the composition may be electrospun with a thickness of greater than about 1 / 8 inch, or greater than about 1 / 4 inch thick, or about 1 / 4 thick, in some embodiments.

[0046] The material can retain many times its weight in water (typically more than about 50 or 70 times its weight in water). This feature allows the material to absorb large amounts of blood, but blood cells cannot penetrate, resulting in a rapid formation of a physical barrier. In various embodiments, the material enhances the clotting cascade when exposed to blood. The material may be used as a fibrous mat that is folded and / or agglomerated to prepare a suitable mass of material for encapsulating the site of heavy bleeding (including bleeding within a body cavity). In some embodiments, the silica fibrous material is processed into a flocculent material. The flocculent material may be loosely agglomerated or may be formed by chopping and / or agglomerating portions of the electrospun fibrous mat. The flocculent material may be used to encapsulate the site of heavy bleeding. Alternatively, the silica fibrous material may be applied as a powder or dust, a gel, a paste, or as an additive to a flowable matrix. Fillers may be added to the material and may include a variety of synthetic and natural polymeric and materials such as poloxamer, polyethylene glycol, polyvinyl alcohol, collagen, gelatin, cellulose, chitosan, and fibrin, among others.

[0047] In some embodiments, the silica fiber composition is processed into a fine powder or dust, and the powder or dust is applied to the bleed. For example, a sheet of silica fiber may be rubbed through one or more screens, and a range of powder sizes is obtained by varying the mesh size. In some embodiments, the powder or dust may be mixed with a topical composition (e.g., a lotion, ointment, paste, cream, foam, or gel). In these embodiments, the topical composition may include one or more medicinal or antimicrobial agents, such as antibiotics, antiseptics, anti-inflammatory agents, or immunosuppressants.

[0048] In various embodiments, the silica fiber composition may then be divided into small fiber pieces that are applied to the bleed. Each resulting fiber piece is an entangled collection of silica fibers rather than a single solid particle. In some embodiments, the electrospun mat may be crushed, cut, ground, crushed, or otherwise broken into smaller pieces that maintain the fiber structure. In some embodiments, the mat (or one or more portions thereof) may be rubbed through one or more screens or sieves, with the mesh size of the screen determining, at least in part, the size of the resulting fiber pieces generated from the electrospun mat. For example, the mat or mat portions may be rubbed through two or more successive screens of decreasing mesh size (e.g., screens having mesh numbers of 100, 200, 300, or even 400) to generate a collection of fiber pieces having a desired size.

[0049] As used herein, the term "fiber fragments" (or "fibrous mat fragments" or simply "fragments") refers to small dust-like particles, parts, or flakes of a fibrous mat having an average dimension greater than the width of at least some of the fibers of the mat (e.g., 5x, 10x, or even 100x). In various embodiments, the average size of the fiber fragments ranges from approximately 20 μm to approximately 200 μm along their long axis. In this manner, fiber fragments resemble a microscopic-scale version of the electrospun mat itself (e.g., an entangled collection of silica fibers), and thus are typically porous. Thus, fiber fragments may be contrasted with other types of microscale particles (e.g., the substantially spherical particles used in colloidal silica), which are each single, separate units or particles rather than a small collection of fibers.

[0050] In some embodiments, the silica fiber is provided with a material that makes it easier to handle and apply to the wound site. For example, the silica fiber material may be combined with a backing material (which in some embodiments may be gauze or other woven material) or may be inside a flexible container (e.g., a bag) made of any material into which the silica fiber material can be emptied or placed at the site of bleeding. FIGS. 1A and 1B show examples where the silica fiber material is provided in a flexible container or on a flexible backing material for application to the wound site. For example, FIG. 1A shows a flexible bag 100. The flexible bag 100 includes the silica fiber material and is closed by using a tie string 110. In various embodiments, the bag 100 includes, consists essentially of, or consists of gauze or a similar material (e.g., combat gauze). FIG. 1B shows another embodiment, where a pad or backing material 120 includes silica fiber material 130 therein and / or thereon. In various embodiments, the pad or backing 120 comprises, consists essentially of, or consists of gauze or a similar material (e.g., combat gauze), In various embodiments, all or part of the periphery of the pad or backing 120 may be adhesive to help keep the pad or backing 120 in place after application.

[0051] In some embodiments, the silica fiber material itself is applied to the wound site without a backing or container. Figure 2 shows an example embodiment in which silica fiber pads are shaped as disks for application to the wound site. As shown, such pads may be stacked and / or stored in a suitable container (e.g., the jar shown in Figure 2).

[0052] In some embodiments, the fiber composition is applied directly to the site of bleeding by wrapping the site with the material in any form and applying as much pressure as possible. The fiber composition absorbs blood and large amounts of fluid, but blood cells cannot penetrate the material, and a physical barrier against further blood loss is quickly formed. In some embodiments, even in the case of severe bleeding (e.g., grade 3 or 4 bleeding), the silica fiber material can stop blood flow within about 60 seconds, or in some embodiments, within about 30 seconds, or in some embodiments, within about 15 seconds. By quickly stopping severe bleeding at the site of injury, the patient can be transported to the surgical facility more quickly and safely. The silica fiber material (or at least a portion thereof) can be easily removed by the physician during the surgical procedure.

[0053] In some embodiments, the blood flow rate at the site of bleeding is sufficient to make direct application of the fiber composition difficult. For example, blood flow from a ruptured blood vessel may resist or prevent contact between the silica fiber material and the damaged blood vessel. Thus, in various embodiments, the fiber composition is applied directly to the site using a delivery device that simultaneously delivers the fiber composition to the wound site while aspirating excess blood at or near the wound site. In this way, direct contact between the fiber composition and the wound site is facilitated.

[0054] 3A-3C are schematic diagrams illustrating an exemplary delivery device 300 for a fiber composition according to an embodiment of the present invention. As shown, the delivery device 300 may include a hollow central bore (or "chamber") 305 that is open at one end. The opposite end may be blocked by a movable plunger 310. As shown in FIG. 3C, the fiber composition 315 may be packed or otherwise placed within the central bore 305, and a user may actuate the plunger 310, forcing the fiber composition 315 out of the central chamber 305 and onto (or at least near) the wound site. As shown in FIGS. 3B and 3C, when the plunger 310 is actuated, the central bore 305 is effectively divided into two separate compartments: a lower compartment through which the fiber composition 315 emerges and into the wound site, and an upper compartment that is separated from the lower compartment by a portion of the plunger 310.

[0055] To facilitate sufficient contact between the fiber composition and the bleeding wound without the fiber composition being detached from the wound by the blood flow, in various embodiments, the delivery device 300 delivers the fiber composition while simultaneously aspirating excess blood. As shown in Figures 3B and 3C, in various embodiments, the delivery device 300 may include an external annular compartment 320 coaxial with the hollow central bore 305. As shown, the external compartment 320 defines an opening 325 that facilitates fluid communication between the wound site and at least the upper compartment of the central bore 305. As shown in Figures 3B and 3C, when the plunger 310 is actuated to deliver the fiber composition to the wound site, the action of the plunger 310 creates suction in the upper compartment of the central bore 305. As a result, excess blood from the wound site (e.g., from one or more heavily bleeding blood vessels) is drawn into the external annular compartment 320 and into the upper compartment of the delivery device 300. In this manner, excess blood or other fluids can be removed from the wound site while the fiber composition is simultaneously applied to the wound site, facilitating direct contact between the fiber composition and the bleeding to be treated.

[0056] 3B and 3C, in some embodiments, the outer annular compartment 320 is also fluidly connected to the lower compartment of the central bore 305 by one or more openings. In this way, excess blood that enters from the lower compartment during application of the fiber composition can also be drawn into the upper compartment.

[0057] In various embodiments, the openings fluidly connecting the outer annular compartment 320 with the wound site and / or the upper compartment are sufficiently small that little or no fiber composition is accidentally aspirated from the wound site. Alternatively or additionally, a filter or screen may be included over the openings to prevent the flow of fiber composition (at least larger pieces thereof) or other solid matter from being aspirated into the outer annular compartment and / or the upper compartment of the delivery device. Also as shown in FIG. 3B, the upper compartment of the central bore may be sealed by an annular gasket 330. The annular gasket 330 reduces or substantially eliminates the entry of solid or liquid material into the upper compartment of the central bore 305 while allowing the movement of the plunger 310.

[0058] In various embodiments, all or a portion of the delivery device 300 comprises, consists essentially of, or consists of one or more biocompatible materials, such as one or more plastics, other polymeric materials, or stainless steel.

[0059] The silica fiber material may be used for the treatment of humans and animals. In some embodiments, the subject is a mammal. The subject may include a veterinary patient, such as a dog, cat, pig, or horse, among others. In some embodiments, the patient is a human patient.

[0060] The World Health Organization includes a grade of bleeding from 0 to 5. In some embodiments, the bleeding is at least a grade 2 bleeding (e.g., a grade 3 or grade 4 bleeding). Grade 2 bleeding is mild, but clinically significant. In some embodiments, the bleeding is a grade 4 bleeding. Grade 4 bleeding is defined as severe bleeding that typically requires a blood transfusion. Grade 5 bleeding is associated with death. In some embodiments, the bleeding is arterial bleeding. Arterial bleeding is often shown to spurt as a rising and falling jet with the pulse. If bleeding is prolonged and when intravenous fluids are given in amounts other than blood, it may appear watery in appearance. In some embodiments, the bleeding is venous bleeding. Venous bleeding is a darker red color and a steady and heavy flow. Blood loss is particularly rapid if large veins are open.

[0061] In some embodiments, the bleeding occurs during or after a surgical procedure. For example, the bleeding may be organ bleeding. In these embodiments, the silica fiber material may be applied directly to the bleeding using portions of a silica fiber mat or in a variety of other forms (e.g., a powder or dust, a paste or gel, or a flowable matrix that includes silica fiber dust).

[0062] In some embodiments, the bleeding is a primary hemorrhage, occurring at the time of injury or surgery. In some embodiments, the bleeding is a rebound hemorrhage. Rebound hemorrhage may occur within 24 hours (usually 4-6 hours) following the primary hemorrhage, and is primarily due to rotation ("slippage") of the ligature, dislodging of the clot, or cessation of reflex vasospasm. In some embodiments, the bleeding is a secondary hemorrhage. Secondary hemorrhage occurs 7-14 days later and is due to infection and sloughing off of the scab.

[0063] In some embodiments, the bleeding is traumatic bleeding. For example, the bleeding is non-compressible bleeding. In some embodiments, the bleeding is a body cavity bleeding. In some embodiments, the injury is a crush injury. In some embodiments, the injury is a gunshot wound or a blast wound.

[0064] In some embodiments, the bleeding is a nosebleed and silica fibrous material is packed inside the nasal cavity.

[0065] In some embodiments, the bleeding is external. For example, the silica fiber material may be formed into a pad or bandage or may be used with various types of conventional bandage materials (e.g., cotton gauze) and wound dressings to facilitate bleeding control.

[0066] In some embodiments, the patient is undergoing treatment to inhibit the coagulation pathway. Such treatment may include heparin (unfractionated or LMWH). Alternatively, the patient may be undergoing treatment with a factor Xa inhibitor or a direct thrombin inhibitor, or other direct inhibitor of the coagulation pathway. In some embodiments, the patient is suffering from an inherited coagulation disorder, such as hemophilia, thrombocytopenia, low platelet count, or von Willebrand's disease.

[0067] Other aspects and embodiments of the invention will be apparent from the following non-limiting examples. EXAMPLES

[0068] Example 1: Preparation of Silica Fiber Composition The SiO2 fibers were prepared using an electrospinning process in which a sol-gel is spun onto a roller system that forms a sheet. The sol-gel is made in two parts. First, TEOS is mixed with ethanol, and a second mixture containing HCl, water, and ethanol is titrated into the mixture. The sol-gel is then aged under controlled conditions for several days before being spun.

[0069] In one example, a first sol was made by weighing 384 grams of (TEOS) tetraethyl orthosilicate 98% and 41.8 grams of anhydrous denatured ethanol and pouring them together. The first sol was placed in a beaker and allowed to sit, and a magnetic stirrer was used to create a homogenous solution. A second sol was made by weighing 41.8 grams of anhydrous denatured ethanol, 16.4 grams of distilled water, and 0.34 grams of hydrochloric acid, then pouring them together and mixing with a magnetic stirrer for 8 seconds until a homogenous second sol was created.

[0070] The second sol was then poured into a titrator positioned above the beaker containing the first sol. The titrator was then used to drip the second sol at about 5 drops / second until a third sol was created that mixed the first and second sols. During the dripping process, the first sol was continuously mixed by a magnetic stirrer while the second sol was dripped into the first sol.

[0071] The mixed tertiary sol was then placed in an enclosure box. A low pressure vacuum was applied by a fan at a medium speed to remove fumes. In the experiment, the temperature inside the box was 72°F and the humidity was 60%. In the experiment, the tertiary sol was left to process for about three (3) days. By slowly aging the sol-gel over several days, the sol-gel slowly transitions and the ideal time for electrospinning can be identified.

[0072] The mixture was stirred daily to reduce the buildup of crystalline structures. With the evaporation of the alcohol solvent, the tertiary sol begins to transform into a sol-gel. The sol-gel may be monitored to determine the approximate amount of C2H4 (ethylene) in the vapor. This may range from about 10-20% relative to the original sol before aging. Once properly gelatinized, the sol-gel is loaded into the electrospinning machine or frozen and stored for electrospinning. Proper gelatinization occurs when the total weight of the sol-gel is about 100 grams to about 180 grams.

[0073] The above example can be appropriately scaled to produce the desired structure, and to further identify the ideal time for electrospinning, a portion of the gel can be dropped into the electric field and the properties of the resulting fibers evaluated.

[0074] 4A-4D are scanning electron microscope (SEM) images of fibers spun according to the present disclosure (50, 100, 200, and 500 micron scales shown). As shown, the fibers are soft, smooth, dense, and continuous (not fractured). Materials with these properties are ideal for treating wounds and animal tissues (e.g., as collagen mimics).

[0075] Figures 5A-5D are SEM images (50, 100, 200, and 500 micron scales shown) of fibers electrospun at non-optimal times (before the sol-gel had fully aged). The fibers appear stiff, with many fractures and agglomerates formed. Figure 6 shows an SEM image (20 micron scale shown) of fibers from the same material. The fibers are noticeably stiff, with many fractures evident.

[0076] FIG. 7 shows a fiber mat spun according to the present disclosure. The flexibility and continuity of the fibers allows the mat to be spun at thicknesses of 1 / 4 inch or more. The mat is soft and pliable to the touch, and the fiber layers can be easily separated to cover the wound bed. FIGS. 8A and 8B compare a silica fiber mat electrospun when the sol-gel was aged according to the present disclosure (FIG. 8A) with a fiber mat spun prematurely, before the sol-gel had optimally aged (FIG. 8B). The material in FIG. 8A is soft to the touch, very pliable, and can be spun to a thickness that is easily handled for application of the fiber layers to the wound site. The material in FIG. 8B is brittle, inflexible, thin, and the fiber layers cannot be easily separated to cover the site of bleeding.

[0077] Example 2: Hemostasis investigation A porcine model was used to investigate the effect of silica fiber compositions according to embodiments of the present invention on hemostasis of fatal limb arterial bleeding. Specifically, muscle tissue was removed to expose the femoral artery, and the artery was severed using a biopunch. After a few seconds of bleeding, silica fiber material was applied with limited pressure to the severed vessel, and the continued bleeding was quickly stopped. The subject survived for 3 hours. During that time, the leg was moved back and forth 10 times and checked for bleeding. The subject was then moved to a sled and pulled 50 yards to simulate a soldier's withdrawal in combat. The wound was then checked for bleeding. After this, the subject was euthanized and the injured vessel was excised and analyzed. A control subject was treated with conventional Quick Clot Combat Gauze (i.e., a soft non-woven gauze impregnated with kaolin to accelerate clotting) for comparison.

[0078] In the experiment, the average blood loss and bleeding time for subjects treated with the silica fiber composition was reduced by approximately half compared to control subjects. The final mean arterial pressure and heart rate were also slightly higher in subjects treated with the silica fiber composition. The body temperature of subjects treated with the silica fiber composition also tended to be lower (i.e., improved) during the study period.

[0079] Histology was performed using hematoxylin and eosin staining after the experiment, as shown in FIG. 9A. As observed in the image, the silica fiber composition (designated as "fiber" on the image) has occluded the arterial injury (i.e., the outlined area designated as "injured artery"), with clotted fibrils and aligned red blood cells present outside the injury site. FIG. 9B shows a Multius Scarlet Blue (MSB) trichrome fibrin stained image of the injury site treated with the silica fiber composition. The image shows that a clot has formed around and within the silica fibers occluding the injury site. The cells growing into the silica fibers are similar to those in the vessel wall. The fibrin fibers are intertwined with the silica fibers, and a clear fibrin bridge (indicated by the darker stained fibrils within the injury site) has formed across the edge of the entire injury site where the silica fibers were applied. This was unexpected for such a short treatment time of such a large injury to a major artery, demonstrating the effectiveness of embodiments of the present invention for controlling and treating bleeding.

[0080] Overall, the silica fiber composition stopped arterial bleeding much faster than the control sample gauze. Pressure could be removed even before the end of the 3-minute treatment period, and no bleeding was observed. Moving the pig's leg did not result in further bleeding. Hemostasis was maintained even while attempting to manually remove the clot. In contrast, the control gauze required the application of more significant pressure, and there was increased bleeding around the gauze for most of the 3-minute treatment period. Unlike the silica fiber composition, the gauze is also designed to be removed after hemostasis, and therefore is not designed to remain in the wound and guide regeneration. The silica fiber composition reduces the time to hemostasis and the total amount of blood loss. It also reduces the number of rebleeding events, facilitates tissue coverage and regeneration, and ultimately improves the chances of survival of heavy bleeding.

[0081] The terms and expressions used in this specification are used as terms and expressions of description and not of limitation. When such terms and expressions are used, there is no intention to exclude any equivalents of the features shown and described or portions thereof. In addition, since specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that other embodiments incorporating the ideas disclosed herein may be used without departing from the spirit and scope of the present invention. The described embodiments should therefore be considered in all respects merely as illustrative and not restrictive. In certain embodiments, for example, the following are provided: (Item 1) A method for treating a hemorrhage in a subject, comprising applying to said hemorrhage an electrospun silica fiber composition in an amount and under conditions sufficient to stop said hemorrhage. (Item 2) 2. The method according to item 1, wherein the silica fiber composition is prepared by electrospinning a sol prepared by 70 wt%-90 wt% tetraethyl orthosilicate (TEOS), 8 wt%-25 wt% ethanol, an acid catalyst, and the balance water. (Item 3) 3. The method according to claim 2, wherein the sol is transformed under conditions of humidity in the range of 40% to 80% and temperature in the range of 50 to 90° F. for a period of 2 to 7 days. (Item 4) 4. The method of claim 3, wherein the sol is not exposed to heat above 150°F or above 100°F. (Item 5) 3. The method according to claim 2, wherein the acid catalyst is HCl. (Item 6) 2. The method according to item 1, wherein the subject is a mammal. (Item 7) 7. The method according to item 6, wherein the subject is a human. (Item 8) 8. The method according to any one of items 1 to 7, wherein said bleeding is at least grade 2 bleeding. (Item 9) The method according to item 8, wherein the bleeding is grade 3 or grade 4 bleeding. (Item 10) 10. The method according to item 9, wherein the bleeding is arterial bleeding. (Item 11) 10. The method according to item 9, wherein the bleeding is venous bleeding. (Item 12) The method according to item 8, wherein the bleeding occurs during or after a surgical procedure. (Item 13) 13. The method according to item 12, wherein the bleeding is organ bleeding. (Item 14) 14. The method according to any one of items 8 to 13, wherein the bleeding is primary bleeding. (Item 15) 14. The method according to any one of items 8 to 13, wherein the bleeding is rebound bleeding. (Item 16) 14. The method according to any one of items 8 to 13, wherein the bleeding is secondary bleeding. (Item 17) 17. The method according to any one of items 1 to 16, wherein the bleeding is traumatic bleeding. (Item 18) 18. The method according to item 17, wherein the bleeding is non-compressible bleeding. (Item 19) 18. The method according to item 17, wherein the bleeding is a body cavity bleeding. (Item 20) 20. The method according to any one of items 17 to 19, wherein the injury is a crush injury. (Item 21) 20. The method according to any one of items 17 to 19, wherein the injury is a gunshot wound or a blast wound. (Item 22) 9. The method according to item 8, wherein the bleeding is nosebleed. (Item 23) 9. The method according to item 8, wherein the bleeding is external. (Item 24) 24. The method according to any one of items 1 to 23, wherein the subject is undergoing treatment that inhibits the coagulation pathway. (Item 25) 24. The method according to any one of items 1 to 23, wherein the subject has a coagulation disorder. (Item 26) 26. The method of claim 25, wherein the subject has hemophilia, thrombocytopenia, low platelet count, or von Willebrand's disease. (Item 27) The silica fiber composition is applied to the bleeding site via a delivery device, the delivery device comprising: a hollow central bore having an upper end and an open lower end; a movable plunger disposed at the upper end of the central bore and actuatable by a user of the delivery device to force the silica fiber composition out of the open lower end of the central bore, a portion of the plunger separating the central bore into a lower compartment and an upper compartment; an annular outer compartment coaxial with the central bore, the outer compartment fluidly connected to the upper compartment of the central bore and defining one or more openings for fluidly connecting with an area proximate the bleeding; 27. The method according to any one of items 1 to 26, wherein when the plunger is actuated to force the silica fiber composition from the open lower end of the central bore towards the bleed, fluid adjacent the bleed is simultaneously aspirated into the outer compartment and into the upper compartment of the central bore. (Item 28) 28. The method of claim 27, wherein the central bore defines one or more openings therethrough that fluidly connect the lower compartment to the annular outer compartment. (Item 29) 1. A delivery device for applying a silica fiber composition proximate to a bleeding area, the delivery device comprising: a hollow central bore having an upper end and an open lower end; a movable plunger disposed at the upper end of the central bore and actuatable by a user of the delivery device to force the silica fiber composition out of the open lower end of the central bore, a portion of the plunger separating the central bore into a lower compartment and an upper compartment; an annular outer compartment coaxial with the central bore, the outer compartment fluidly connected to the upper compartment of the central bore and defining one or more openings for fluidly connecting with an area proximate the bleeding; The delivery device, wherein when the plunger is actuated to force the silica fiber composition from the open lower end of the central bore into the bleed, fluid adjacent to the bleed is simultaneously drawn into the outer compartment and into the upper compartment of the central bore. (Item 30) 30. The delivery device of claim 29, wherein the central bore defines one or more openings therethrough that fluidly connect the lower compartment to the annular outer compartment. (Item 31) 30. The delivery device of claim 29, further comprising the silica fiber composition disposed within the lower compartment of the central bore. (Item 32) 32. The delivery device of claim 31 , wherein the silica fiber composition comprises a plurality of silica fibers. (Item 33) 32. The delivery device of claim 31 , wherein the silica fiber composition comprises a powder or dust. (Item 34) 1. A kit for treating bleeding in a subject, comprising: a silica fiber composition; and a delivery device for applying the silica fiber composition to the bleed. (Item 35) The delivery device comprises: a hollow central bore having an upper end and an open lower end; a movable plunger disposed at the upper end of the central bore and actuatable by a user of the delivery device to force the silica fiber composition out of the open lower end of the central bore, a portion of the plunger separating the central bore into a lower compartment and an upper compartment; an annular outer compartment coaxial with the central bore, the outer compartment fluidly connected to the upper compartment of the central bore and defining one or more openings for fluidly connecting with an area proximate the bleeding; 35. The kit of claim 34, wherein when the plunger is actuated to force the silica fiber composition out of the open lower end of the central bore and into the bleed, fluid adjacent the bleed is simultaneously aspirated into the outer compartment and into the upper compartment of the central bore. (Item 36) Item 36. The kit of item 35, wherein the central bore of the delivery device defines one or more openings therethrough that fluidly connect the lower compartment to the annular outer compartment. (Item 37) 35. The kit according to item 34, wherein the silica fiber composition is an electrospun silica fiber composition. (Item 38) 35. The kit according to item 34, wherein the silica fiber composition comprises a plurality of silica fibers. (Item 39) 35. The kit according to item 34, wherein the silica fiber composition comprises a powder or dust.

Claims

1. 1. An electrospun silica fiber composition for treating bleeding in a subject, wherein the electrospun silica fiber composition is applied to the bleeding in an amount and under conditions sufficient to stop the bleeding, the silica fiber composition being prepared by electrospinning a sol prepared from 70% to 90% by weight tetraethyl orthosilicate (TEOS), 8% to 25% by weight ethanol, an acid catalyst, and the balance water, and the bleeding is at least Grade 2 bleeding.

2. 10. The composition of claim 1, wherein the sol is allowed to transition for 2 to 7 days under conditions of humidity ranging from 40% to 80% and temperature ranging from 50 to 90°F.

3. 3. The composition of claim 2, wherein the sol is not exposed to heat in excess of 150°F or 100°F.

4. The composition of claim 1 , wherein the acid catalyst is HCl.

5. The composition of claim 1, wherein the subject is a mammal.

6. The composition of claim 5 , wherein the subject is a human.

7. The composition of claim 1, wherein the bleeding is grade 3 or grade 4 bleeding.

8. The composition of claim 7, wherein the bleeding is arterial bleeding.

9. The composition of claim 7, wherein the bleeding is venous bleeding.

10. The composition of claim 1, wherein the bleeding occurs during or after a surgical procedure.

11. The composition of claim 10, wherein the bleeding is organ bleeding.

12. The composition of claim 11, wherein the organ is the liver, heart, lung, kidney, pancreas, stomach, or intestine.

13. The composition of claim 1, wherein the bleeding is primary bleeding.

14. The composition of claim 1, wherein the bleeding is rebound bleeding.

15. The composition of claim 1, wherein the bleeding is secondary bleeding.

16. The composition of claim 1, wherein the bleeding is traumatic bleeding.

17. The composition of claim 16, wherein the bleeding is non-compressible bleeding.

18. The composition of claim 16, wherein the bleeding is a body cavity bleeding.

19. The composition of claim 16, wherein the injury is a crush injury.

20. The composition of claim 16, wherein the injury is a gunshot wound or a blast wound.

21. The composition of claim 1 , wherein the bleeding is external.

22. The composition of claim 1, wherein the subject is undergoing treatment that inhibits the coagulation pathway.

23. The composition of claim 1, wherein the subject has a coagulation disorder.

24. 24. The composition of claim 23, wherein the subject has hemophilia, thrombocytopenia, low platelet count, or von Willebrand's disease.

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