The present invention relates to blood clotting devices (also referred to as hemostatic agents) and methods of controlling bleeding and, more particularly, to blood clotting materials and compositions for use as bleeding control devices.
Blood is a liquid tissue that includes red cells, white cells, corpuscles, and platelets dispersed in a liquid phase. The liquid phase is plasma, which includes acids, lipids, solublized electrolytes, and proteins. The proteins are suspended in the liquid phase and can be separated out of the liquid phase by any of a variety of methods such as filtration, centrifugation, electrophoresis, and immunochemical techniques. One particular protein suspended in the liquid phase is fibrinogen. When bleeding occurs, the fibrinogen reacts with water and thrombin (an enzyme) to form fibrin, which is insoluble in blood and polymerizes to form clots.
In a wide variety of circumstances, animals, including humans, can be wounded. Often bleeding is associated with such wounds. In some instances, the wound and the bleeding are minor, and normal blood clotting functions in addition to the application of simple first aid are all that is required. Unfortunately, however, in other circumstances, substantial bleeding can occur. These situations usually require specialized equipment and materials as well as personnel trained to administer appropriate aid. If such aid is not readily available, excessive blood loss can occur. When bleeding is severe, sometimes the immediate availability of equipment and trained personnel is still insufficient to stanch the flow of blood in a timely manner.
Moreover, severe wounds can often be inflicted in very remote areas or in situations, such as on a battlefield, where adequate medical assistance is not immediately available. In these instances, it is important to stop bleeding, even in less severe wounds, long enough to allow the injured person or animal to receive medical attention.
In an effort to address the above-described problems, materials have been developed for controlling excessive bleeding in situations where conventional aid is unavailable or less than optimally effective. Although these materials have been shown to be somewhat successful, they are not effective enough for traumatic wounds and tend to be expensive. Furthermore, these materials are sometimes ineffective in all situations and can be difficult to apply as well as remove from a wound. Additionally, or alternatively, they can produce undesirable side effects.
Compositions for promoting the formation of clots in blood have also been developed. Such compositions generally comprise zeolites and binders. In a typical zeolite/binder composition, the water content is estimated to be about 1.54% or less. The water content is estimated by measuring the mass of material before and after heating at 550 degrees C. (Loss on Ignition (LOI) at 550 degrees C.). Higher temperatures are sometimes used for LOI calculations, but procedures that utilize these higher temperatures increase the loss of chemical compounds other than water.
Based on the foregoing, it is a general object of the present invention to provide a bleeding control device that overcomes or improves upon the prior art.
According to one aspect of the present invention, a composition for promoting the formation of clots in blood comprises a zeolite and a binder. In such a composition, the moisture content of the zeolite is adjusted by drying, re-hydrating, or a combination of drying and re-hydrating such that the zeolite has a specific moisture content. Alternatively, the composition may be fully saturated with water and subsequently dried to a specific water content. In the drying of the zeolite, the bound water is removed to allow the crystalline structure of the zeolite to remain intact. In the re-hydration of the zeolite, the most active adsorption sites are hydrated first and then less active sites are hydrated. As the zeolite's degree of hydration increases, the heat of hydration decreases. More specifically, when the composition is applied to the blood, water in the blood is adsorbed by the zeolite. Upon adsorption of this water, heat is generated. At higher levels of hydration (hydration of the zeolite prior to its application to blood), less heat is generated when the composition is applied to blood. Thus, when the composition is applied to blood directly at a wound site, the amount of heat transferred to the tissue surrounding the wound site is reduced.
According to another aspect of the present invention, a method of forming a blood-clotting composition comprises the steps of providing a zeolite in hydrated form and adjusting a moisture content of the zeolite to have a specific moisture content such that upon application of the composition to a wound, a heat of hydration is reduced and a heat transferred to the wound is reduced.
According to another aspect of the present invention, a method of clotting blood flowing from a wound comprises the steps of applying a zeolite to the wound and maintaining the zeolite in contact with the wound for a predetermined amount of time, the zeolite having an adjusted moisture content and being capable of producing a controllable exothermic effect on the wound.
One advantage of the present invention is that it is easily applied to an open wound. It can be readily removed from sterilized packaging and deposited directly at the points from which blood emanates to dress the wound.
Another advantage of the present invention is that the rate of water adsorption is dramatically reduced as the degree of hydration increases from about 0.1% to about 4%. After about 4%, the rate of adsorption is slower. Also, after about 4%, the rate of adsorption changes more slowly. In application of the composition to promote the clotting of blood, slower water adsorption is advantageous for two reasons. First, the humidity and temperature of the packaging environment has less of an affect, thereby allowing material to be exposed to the environment for a longer period of time without significantly changing the pre-hydration level. Second, the slower rate of water adsorption allows the heat of hydration to be dissipated over a longer period of time. Therefore, the composition is heated to a lower maximum temperature. Thus, less heat is transferred to the tissue of a wound without losing product efficacy (formation of clots in blood).
The present invention is able to effectively clot traumic bleeding of wounds better than other available methods for treating similar wounds. For example, in a lethal femoral swine model in which several blood clotting materials were evaluated, the material of the present invention was the only material proven to have a morbidity rate of 0% including a standard pressure dressing.
Disclosed herein are compositions and methods directed to the clotting of blood and the forming of blood clotting compositions. The compositions generally include molecular sieves for minimizing or stopping bleeding by absorbing at least portions of the liquid phases of blood, thereby promoting clotting. The methods generally include the application of molecular sieves to bleeding wounds to provide dressings and removing components of the blood to facilitate the formation of clots.
In one embodiment of the present invention, a molecular sieve comprises a zeolite and a binder. As used herein, the term “zeolite” refers to a crystalline form of aluminosilicate that may include several ionic species including sodium and calcium moieties. The preferred molecular structure of the zeolite is referred to as an “A-type” crystal. As used herein, the term “A-type crystal” is intended to indicate a crystal having a cubic crystalline structure and round holes. The zeolite may be ion-exchanged to include a specific cation, for example, calcium, sodium, potassium, silver, or magnesium, or any combination of the foregoing. Suitable zeolites for use in the applications disclosed herein are also preferably nanoporous so as to provide increased surface areas. As used herein, the term “nanoporous” is intended to indicate an average pore diameter of about 3 angstroms to about 5 angstroms.
In another embodiment of the present invention, the zeolite comprises irregularly-shaped granular material that is prepared by grinding larger particles and then selecting material that will pass through a 16 mesh sieve screen but will not pass through a 40 mesh sieve screen. The resulting zeolite is a composition of irregular granules that range in size from 0.4 millimeters (mm) in diameter to 0.8 mm in diameter.
Zeolites for use in the disclosed applications may be naturally occurring or synthetically produced. Numerous varieties of naturally occurring zeolites are found as deposits in sedimentary environments as well as in other places. Naturally occurring zeolites that may be applicable to the compositions and methods described herein include, but are not limited to, analcite, chabazite, heulandite, natrolite, stilbite, and thomosonite. Synthetically produced zeolites that may also find use in the compositions and methods described herein are generally produced by processes in which rare earth oxides are substituted by silicates, alumina, or alumina in combination with alkali or alkaline earth metal oxides.
The binder is preferably clay-based and may further include fillers (e.g., aluminum sulfate) or thickening agents that facilitate the selective application of the zeolite in various forms (e.g., as a paste, gel, powder, or erodable solid member). Natural clays that may provide suitable bases include, but are not limited to, kaolin, kaolinite, bentonite, montmorillonite, combinations of the foregoing clays, and the like. Modified clays such as polyorganosilcate graft polymers may also provide suitable bases.
In the preparation of the zeolite for a blood clotting composition, the moisture content of the zeolite is adjusted by drying, re-hydrating, or a combination of drying and re-hydrating the zeolite such that the zeolite has a specific moisture content. A fully hydrated zeolite has a moisture content of about 20 weight percent (wt. %). Drying of the zeolite may be effected by the application of heat. Upon heating, adsorbed water bound in the crystalline structure is driven off without altering the structure itself or detracting from its integrity. The dried zeolite may then be re-hydrated. The efficacy provided by the molecular sieve material/zeolite is enhanced by rehydrating the molecular sieve material/zeolite to a hydration level ranging between 1% and 15%. In addition, it has been found that this hydration level more preferables between about 2% and 8%. The exothermia caused by the reaction of the molecular sieve material/zeolite with the blood flowing from an open wound can be reduced to a level which virtually eliminates any potential damage to the surrounding Upon drying or drying and re-hydrating, in another example, the zeolite contains about 1.55 wt. % to about 10 wt. % moisture, and preferably about 1.55 wt. % to about 4 wt. % moisture. Alternatively, the drying process can be stopped before the material is completely dehydrated. The final hydration of the material can be controlled by monitoring and controlling the temperature of zones of a drying apparatus in which the material is dried.
The hydrated zeolite material also generates less heat upon being fully-saturated with water in the application of the zeolite to the blood. In particular, the heat of hydration is inversely proportional to the moisture content. Therefore, a zeolite hydrated to a moisture content of 4 wt. % will generate measurably less heat than a zeolite that has been fully dehydrated to less than 0.1 wt. %. Both materials, however, will be fully-saturated with water upon application to a bleeding wound. Thus, when applied to a bleeding wound under conditions of actual use, the exothermic effects and heat transferred to the wound are reduced. Therefore, upon application of the composition of the present invention to a bleeding wound, less heat is transferred to the tissue of the wound.
As stated above, upon treating wounds with the present invention, the remaining blood, which includes cells, corpuscles, platelets, and plasma, is concentrated. The platelets aggregate and interact with collagen, phospholipids, and lipid-containing proteins in the plasma. The aggregation of the platelets provide nuclei upon which fibrin binds to form a clot. Cells from the blood subsequently combine with the clot to form a mass. When blood emanates from the wound, the formation of the mass from the clot causes the flow of blood to cease, thereby eliminating further loss of blood. The blood pressure will often noticably increase upon application of the present invention due to cessation of blood loss.
A molecular sieve containing partially re-hydrated zeolite was added to normal pooled plasma. Upon completion of the ensuing reaction, the plasma was separated into two phases, namely, a heavy phase and a supernatant phase. The heavy phase included the typical blood plasma components as well as the reacted zeolite. The supernatant phase was tested to determine the levels of PT, aPTT, and fibrinogen, where “PT” is prothrombin time and “aPTT” is activated partial thromboplastin time. As used herein, PT and aPPT are assays that provide time values that are compared to other samples or to a hemotological standard. The time values are used indirectly to suggest the levels of clotting factors present in pooled plasma. A control comprising serum was also tested to determine the levels of the same components. In a comparison of the supernatant phase to the control, it was noted that the PT, aPTT, and fibrinogen levels were comparable, thereby suggesting that factors indicative of the clotting of blood were depleted by the addition of the molecular sieve containing partially re-hydrated zeolite.
Varying amounts of a molecular sieve containing zeolite were added to 1 milliliter (ml) samples of normal pooled plasma. In the first sample, 200 milligram (mg) of the molecular sieve was added and reacted, and a temperature increase of 9 centigrade (C) degrees was observed. In the second sample, about 3.8 mg of the molecular sieve was added and reacted, and a temperature increase of less than 1 C. degree was observed.
Although this invention has been shown and described with respect to the detailed embodiments thereof, it will be understood by those of skill in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed in the above detailed description, but that the invention will include all embodiments falling within the scope of the appended claims.
This application claims the benefit of U.S. Provisional Patent Application No. 60/502,571 filed Sep. 12, 2003, entitled “Blood Clotting Compositions and Wound Dressings,” to Francis X. Hursey, the contents of which are incorporated herein by reference.
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