Patent Application
20080097271
Disclosed herein are hemostatic devices and hemostatic agents that are applicable to bleeding wounds to promote hemostasis. The hemostatic agents generally include two-component mixtures of particles having hemostatic qualities, such mixtures being contained within mesh bags, perforated containers, or similar devices that, when brought into contact with a bleeding wound, can minimize or stop blood flow by absorbing at least portions of the liquid phases of the blood, thereby facilitating clotting. The mixtures generally include particles of a molecular sieve material and particles of a clay material. The present invention is not limited to two-component mixtures, however, as other materials (e.g., anti-infective agents and the like) in particle form may be included as third or subsequent components.
In one preferred embodiment of the present invention, the molecular sieve material is a zeolite and the clay material is kaolin. The present invention is not limited in this regard, however, as other molecular sieve materials and other clays are within the scope of the present invention. Bioactive glasses, siliceous oxides, diatomaceous earth, and combinations thereof may also be used in place of (or in addition to) either or both the zeolite and the clay.
As used herein, the term “zeolite” refers to a crystalline form of aluminosilicate having one or more ionic species such as, for example, calcium and sodium moieties and the ability to be dehydrated without experiencing significant changes in the crystalline structure. Typically, the zeolite is a friable material that includes oxides of calcium, sodium, aluminum, and silicon in addition to water. The calcium portion contains crystals that are about 5 angstroms in size, and the sodium portion contains crystals that are about 4 angstroms in size. The preferred molecular structure of the zeolite is an “A-type” crystal, namely, one having a cubic crystalline structure that defines round or substantially round openings. One preferred zeolite is that designated as “5A,” which indicates a crystal size of about 5 angstroms and having a cubic crystalline structure defining round or substantially round openings.
The zeolites may be mixed with or otherwise used in conjunction with other materials having the ability to be dehydrated without significant changes in crystalline structure. Such materials include, but are not limited to, magnesium sulfate, sodium metaphosphate, calcium chloride, dextrin, combinations of the foregoing materials, and hydrates of the foregoing materials.
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 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.
Various materials may be mixed with, associated with, or incorporated into the zeolites to maintain an antiseptic environment at the wound site or to provide functions that are supplemental to the clotting functions of the zeolites. Exemplary materials that can be used include, but are not limited to, pharmaceutically-active compositions such as antibiotics, antifungal agents, anti-infective agents, antimicrobial agents, anti-inflammatory agents, analgesics, antihistamines (e.g., cimetidine, chloropheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride), compounds containing silver ions, and the like. Other materials that can be incorporated to provide additional hemostatic functions include ascorbic acid, tranexamic acid, rutin, and thrombin. Botanical agents having desirable effects on the wound site may also be added. Any of the foregoing materials, individually or in combination, may also be present in particle form and blended with the particles of clay and/or the zeolite particles.
For use in the present invention, the zeolite is preferably in particle form. As used herein, “particles” include beads, pellets, granules, rods, or any other surface morphology or combination of surface morphologies. Irrespective of the surface morphology, the zeolite particles are about 0.2 mm (millimeters) to about 10 mm, preferably about 0.5 mm to about 5 mm, and more preferably about 1 mm to about 2 mm in effective diameter. The effective diameter is the average length of a plurality of imaginary straight lines drawn through the geometric center of a particle.
The particle form of the zeolite may be obtained by any suitable operation. For example, particilized zeolite may be obtained from powder stock by any suitable method such as extrusion, pelletizing, or the like. Particlized zeolite may also be obtained by rolling, pulverizing, or otherwise crushing larger chunks of zeolite. The present invention is not limited in this regard, however, as other methods of manipulating the zeolite into particle form are within the scope of the present invention.
As used herein, the term “clay” refers to a crystalline form of hydrated aluminum silicate. The crystals of clay are irregularly shaped and insoluble in water. The combination of some types of clay with water may produce a mass having some degree of plasticity. Depending upon the type of clay, the combination thereof with water may produce a colloidal gel having thixotropic properties.
The clay utilized in the hemostatic agents and devices of the present invention is preferably kaolin, which is an aluminum phyllosilicate comprising about 50% alumina, about 50% silica, and trace impurities. Because of its high purity, kaolin has a high fusion point and is the most refractory of all clays, thus making it suitable for ceramic compositions, refractory processes, catalytic processes, and other industrial uses as well as in cosmetics, pharmaceuticals, and water treatment systems.
More preferably, the clay is Edgar's plastic kaolin (hereinafter “EPK”), which is a water-washed kaolin clay that is mined and processed in and near Edgar, Fla. Edgar's plastic kaolin has desirable plasticity characteristics, is castable, and when mixed with water produces a thixotropic slurry. Other clays such as attapulgite or bentonite are also within the scope of the present invention and can be used individually, in combination with each other, or in combination with kaolin.
The EPK used in the present invention is particlized, dried, and fired to about 600 degrees C. In order to achieve a suitably homogenous mixture of the EPK to form the particles, a relatively high shear is applied to a mass of the EPK using a suitable mixing apparatus. Prior to shearing, the water content of the clay is measured and adjusted to be about 20% by weight to give a sufficiently workable mixture for extrusion and subsequent handling.
During the firing of the EPK, the material is vitrified. Vitrification is effected via repeated melting and cooling cycles to allow the EPK (or other clay material) to be converted into a glassy substance. With increasing numbers of cycles, the crystalline structure is broken down to result in an amorphous composition. The amorphous nature of the EPK allows it to maintain its structural integrity when subsequently wetted. As a result, the EPK maintains its structural integrity when wetted during use, for example, when applied to blood.
As with the zeolite, the particles of clay may be beads, pellets, granules, rods, or any other surface morphology or combination of surface morphologies. Irrespective of the surface morphology, the clay particles are about 0.2 mm to about 10 mm, preferably about 0.5 mm to about 5 mm, and more preferably about 1 mm to about 2 mm in effective diameter.
The clay particles can be produced by any of several various methods. Such methods include mixing, extrusion, spheronizing, and the like. Equipment that can be utilized for the mixing, extruding, or spheronizing of the clay is available from Caleva Process Solutions Ltd. in Dorset, United Kingdom. Other methods include the use of a fluid bed or a pelletizing apparatus. Fluid beds for the production of clay particles are available from Glatt Air Technologies in Ramsey, N.J. Disk pelletizers for the production of clay particles are available from Feeco International, Inc., in Green Bay, Wis. Preferably, the clay is extruded through a suitable pelletizing device. The present invention is not limited in this regard, however, as other devices and methods for producing particlized clay are within the scope of the present invention.
In formulating the hemostatic agent for use with a hemostatic device, the particles of zeolite are blended and commingled with the particles of clay. The sizes of the particles for each of the zeolite and the clay are similar. Furthermore, the amounts of zeolite particles and clay particles is comparable. Such amounts may be determined on a weight basis or a volume basis. The present invention is not limited in this regard, however, as the particle sizes of each component may be dissimilar and/or the amounts of each component may be disparate. Variation in the particle sizes and/or the amounts of each component allows any heat generated from the application of the hemostatic agent to a bleeding wound to be modulated as desired.
It is believed that the cellular clotting mechanisms of both molecular sieve material and clay activate certain contact factors when applied to blood. More specifically, it is believed that zeolite and kaolin (particularly EPK) are different but complementary. While each material exhibits hemostatic qualities on its own, it is likely that the differences in the molecular structures of each initiate different mechanisms by which water in blood is absorbed to facilitate clotting functions.
Referring now to
The mesh 12 is defined by interconnected strands, filaments, or strips of material. The strands, filaments, or strips can be interconnected in any one or a combination of manners including, but not limited to, being woven into a gauze, intertwined, integrally-formed, and the like. Preferably, the interconnection is such that the mesh can flex while substantially maintaining the dimensions of the openings defined thereby. The material from which the strands, filaments or strips are fabricated may be a polymer (e.g., nylon, polyethylene, polypropylene, polyester, or the like), metal, fiberglass, or an organic substance (e.g., cotton, wool, silk, or the like).
Referring now to
To apply the pouch 10 to a bleeding wound, the pouch is removed from the packaging and placed on the bleeding wound. The hemostatic agent 14 in the mesh 12 contacts the tissue of the wound and/or the blood, and at least a portion of the liquid phase of the blood is adsorbed by the zeolite material, thereby promoting the clotting of the blood.
Another embodiment of the present invention is a pad which is shown at 20 with reference to
The mesh 12 is stitched, glued, clamped, or otherwise mounted to the support 22. The support 22 comprises an undersurface 24 against which the hemostatic agent 14 is held by the container 12 and a top surface 26. The undersurface 24 is impermeable to the hemostatic agent 14 (migration of the particles into the support 22 is prevented) and is further resistant to the absorption of water or other fluids. The top surface 26 is capable of having a pressure exerted thereon by a person applying the pad 20 to a bleeding wound or by a weight supported on the top surface 26. The entire support 22 is rigid or semi-rigid so as to allow the application of pressure while minimizing discomfort to the patient.
To apply the pad 20 to a bleeding wound, the pad 20 is removed from its packaging and placed on the bleeding wound. As with the pouch of the embodiment of
Referring now to
The substrate 52 is a plastic or a cloth member that is conducive to being retained on the skin of an injured person or animal on or proximate a bleeding wound. An adhesive 54 is disposed on a surface of the substrate 52 that engages the skin of the injured person or animal. Particularly if the substrate 52 is a non-breathable plastic material, the substrate may include holes 56 to allow for the dissipation of moisture evaporating from the skin surface.
The in vitro clot times of 5A zeolite granules and of 5A zeolite pellets was measured. The granules had an average particle size of about 0.7 mm (0.3 mm to about 1.0 mm), and the pellets had an average effective diameter of about 1.6 mm ( 1/16 inch). Referring to
Referring again to
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.
